Research Topics
Genomes and GenesSpecies | Andrew McMahonSummaryAffiliation: Harvard University Country: USA Publications
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Publications
Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitorsStephen J Rodda
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Development 133:3231-44. 2006..These data demonstrate that commitment within the osteoblast lineage requires sequential, stage-specific, Ihh and canonical Wnt/beta-catenin signaling to promote osteogenic, and block chondrogenic, programs of cell fate specification...
Using mechanistic Bayesian networks to identify downstream targets of the sonic hedgehog pathwayAbhik Shah
Bioinformatics Program, University of Michigan, Ann Arbor, MI 48109, USA
BMC Bioinformatics 10:433. 2009..The topology of a biological pathway provides clues as to how a pathway operates, but rationally using this topology information with observed gene expression data remains a challenge...
GUDMAP: the genitourinary developmental molecular anatomy projectAndrew P McMahon
Department of Molecular and Cellular Biology and Harvard Stem Cell Institute, Harvard University, 16, Divinity Avenue, Cambridge, MA 02138, USA
J Am Soc Nephrol 19:667-71. 2008..Presented here is a brief overview of the Genitourinary Developmental Molecular Anatomy Project effort...
Developmental roles and clinical significance of hedgehog signalingAndrew P McMahon
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Curr Top Dev Biol 53:1-114. 2003..This review focuses on the developing systems themselves, providing a comprehensive survey of the role of Hedgehog signaling in each of these. We also discuss the increasing significance of Hedgehog signaling in the clinical setting...
Evidence that FGF8 signalling from the midbrain-hindbrain junction regulates growth and polarity in the developing midbrainS M Lee
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, Cambridge, MA 02138, USA
Development 124:959-69. 1997..Taken together our results suggest that FGF8 signalling from the isthmus has a key role in coordinately regulating growth and polarity in the developing mesencephalon...
A 5.5-kb enhancer is both necessary and sufficient for regulation of Wnt-1 transcription in vivoP S Danielian
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Dev Biol 192:300-9. 1997..Our results show that the 5.5-kb enhancer is both necessary and sufficient for Wnt-1 expression in vivo...
Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somiteJ A McMahon
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, Cambridge, Massachusetts 02138, USA amcmahon biosun harvar d edu
Genes Dev 12:1438-52. 1998..Together these data demonstrate that inhibition of BMP signaling by axially secreted Noggin is an important requirement for normal patterning of the vertebrate neural tube and somite...
Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1P M Lewis
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Cell 105:599-612. 2001..Thus, cholesterol modification is essential for the normal range of signaling. It also appears to be necessary for appropriate modulation of signaling by the Shh receptor, Ptc1...
Regionalization of Sonic hedgehog transcription along the anteroposterior axis of the mouse central nervous system is regulated by Hnf3-dependent and -independent mechanismsD J Epstein
Developmental Genetics Program and Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, and Department of Cellular, Molecular and Developmental Biology, Harvard University, Cambridge MA, USA
Development 126:281-92. 1999..Taken together, our results support the existence of Hnf3-dependent and -independent mechanisms in the direct activation of Shh transcription within the CNS and axial mesoderm...
Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse nodeX M Zhang
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Cell 105:781-92. 2001..Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis.[Dedicated to Rosa Beddington, a pioneer in mammalian embryology]...
Sonic hedgehog regulates proliferation and inhibits differentiation of CNS precursor cellsD H Rowitch
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
J Neurosci 19:8954-65. 1999..Thus, Hedgehog signaling may contribute to CNS tumorigenesis by directly enhancing proliferation and preventing neural differentiation in selected precursor cells...
Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of the mammalian toothH R Dassule
The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Dev Biol 202:215-27. 1998..Thus, there are distinct targets for all three pathways. Interestingly, both Bmp and Wnt signaling activate Lef1, making it a candidate for integrating the two distinct signaling pathways...
Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse nodeX M Zhang
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Cell 106:781-92. 2001..Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis...
Pax-2 expression in the murine neural plate precedes and encompasses the expression domains of Wnt-1 and En-1D H Rowitch
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Mech Dev 52:3-8. 1995..Pax-5 expression commences later, at the 3-somite stage. Thus, the spatial and temporal expression of Pax-2 is consistent with a possible regulatory role in the activation of Wnt-1 and En-1...
Antagonizing cAMP-dependent protein kinase A in the dorsal CNS activates a conserved Sonic hedgehog signaling pathwayD J Epstein
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Development 122:2885-94. 1996..As both of these are targets of Drosophila Hh signaling, our data point to an evolutionary conservation in both the mechanisms of signaling and the effectors of the signaling pathway...
T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specificationT P Yamaguchi
Department of Molecular Biology, Biological Laboratories, Harvard University, Cambridge, Massachusetts 02138 USA
Genes Dev 13:3185-90. 1999..Our results suggest that Wnt3a, signaling via Brachyury, modulates a balance between mesodermal and neural cell fates during gastrulation...
Engrailed-1 as a target of the Wnt-1 signalling pathway in vertebrate midbrain developmentP S Danielian
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 383:332-4. 1996..This suggests that a key role of Wnt-1 signalling is to maintain En expression and that this aspect of the Wnt-1/engrailed interaction has been conserved from flies to mice...
Evidence that preaxial polydactyly in the Doublefoot mutant is due to ectopic Indian Hedgehog signalingY Yang
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, Cambridge, MA 02138, USA
Development 125:3123-32. 1998..3 centimorgans, suggesting that Dbf mutation may cause an exceptionally long-range disruption of Ihh regulation. Although this leads to ectopic activation of Ihh, normal expression of Ihh in the cartilaginous elements is retained...
Novel regulatory interactions revealed by studies of murine limb pattern in Wnt-7a and En-1 mutantsJ A Cygan
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, Cambridge, Massachusetts 02138, USA
Development 124:5021-32. 1997..Unlike the normal AER, ectopic AER formation is dependent upon Wnt-7a activity, indicating that distinct genetic mechanisms may be involved in primary and secondary AER formation...
Sonic hedgehog signaling is essential for hair developmentB St-Jacques
Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Curr Biol 8:1058-68. 1998..To address the role of Shh in the hair follicle, we have examined Shh null mutant mice...
Hedgehog signals regulate multiple aspects of gastrointestinal developmentM Ramalho-Santos
Department of Molecular and Cellular Biology, and Howard Hughes Medical Institute, Harvard University, Divinity Avenue, Cambridge, Massachusetts 02138, USA
Development 127:2763-72. 2000..These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations...
GDNF induces branching and increased cell proliferation in the ureter of the mouseC V Pepicelli
Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Dev Biol 192:193-8. 1997..These results support a model in which GDNF supplied by the mesenchyme regulates growth and branching in the metanephric kidney through the local regulation of ureter tip-specific factors...
Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding proteinP T Chuang
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 397:617-21. 1999..Our findings support a model in which Hip attenuates Hedgehog signalling as a result of binding to Hedgehog proteins: a negative regulatory feedback loop established in this way could thus modulate the responses to any Hedgehog signal...
Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarityY Echelard
Harvard University, Department of Biochemistry, Molecular Biology, and Cellular and Developmental Biology, Cambridge, Massachusetts 02138
Cell 75:1417-30. 1993..Ectopic expression of Shh in the mouse CNS leads to the activation of floor plate-expressed genes. These results suggest that Shh may play a role in the normal inductive interactions that pattern the ventral CNS...
Regulation of pancreas development by hedgehog signalingM Hebrok
Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
Development 127:4905-13. 2000..Defects in hedgehog signaling may lead to congenital pancreatic malformations and glucose intolerance...
Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4K Stark
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138
Nature 372:679-83. 1994..Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development...
Pax-2 regulatory sequences that direct transgene expression in the developing neural plate and external granule cell layer of the cerebellumD H Rowitch
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Brain Res Dev Brain Res 117:99-108. 1999..Successful misexpression of Sonic hedgehog demonstrates that Pax-2 regulatory sequences should prove generally useful for transgenic gain-of-function approaches in mice...
A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryoT P Yamaguchi
Department of Molecular and Cellular Biology, Biological Laboratories, Harvard University, Cambridge, MA 02138, USA
Development 126:1211-23. 1999..The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells...
Sonic hedgehog regulates branching morphogenesis in the mammalian lungC V Pepicelli
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Curr Biol 8:1083-6. 1998..In addition, the transcription of several mesenchymally expressed downstream targets of Shh is abolished. These results highlight the importance of epithelially derived Shh in regulating branching morphogenesis of the lung...
Cell death in the CNS of the Wnt-1 mutant mouseG N Serbedzija
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
J Neurobiol 31:275-82. 1996..Thus, programmed cell death plays a role in the loss of the metencephalon, but apparently does not contribute to the earliest aspect of the mutant phenotype, namely the loss of the midbrain...
Analysis of neural crest cell migration in Splotch mice using a neural crest-specific LacZ reporterG N Serbedzija
Cardiovascular Research Center, Massachusetts General Hospital East, Charlestown 02129, USA
Dev Biol 185:139-47. 1997....
Early mouse development: lessons from gene targetingB St-Jacques
Department of Molecular and Cellular Biology, Harvard University, The Biological Laboratories, 16 Divinity Avenue, Cambridge, Massachusetts, 02138 USA
Curr Opin Genet Dev 6:439-44. 1996..Finally, recent technical advances allow the creation of conditional knockouts as well as large chromosomal alterations...
Induction of dopaminergic neuron phenotype in the midbrain by Sonic hedgehog proteinM Z Wang
Ontogeny, Inc, Cambridge, Massachusetts 02139, USA
Nat Med 1:1184-8. 1995..These results suggest that Sonic hedgehog may have utility in the induction of clinically important cell types...
Cystic malformation of the posterior cerebellar vermis in transgenic mice that ectopically express Engrailed-1, a homeodomain transcription factorD H Rowitch
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
Teratology 60:22-8. 1999..These observations raise the possibility that abnormal regulation of Engrailed genes, or targets of Engrailed, may be involved in the pathogenesis of cystic central nervous system malformations of the posterior fossa in humans...
Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathwaysS J Karp
Harvard University, Department of Molecular Biology, The Biolabs, Cambridge, MA 02138, USA
Development 127:543-8. 2000..This identifies Ihh as a coordinator of skeletal growth and morphogenesis, and refines the role of PTHrP in mediating a subset of Ihh's actions...
Sonic hedgehog regulates growth and morphogenesis of the toothH R Dassule
Department of Molecular and Cellular Biology, The Biolabs, Divinity Avenue, Cambridge, MA 02138, USA
Development 127:4775-85. 2000..These studies demonstrate that Shh regulates growth and determines the shape of the tooth. However, Shh signaling is not essential for differentiation of ameloblasts or odontoblasts...
Sertoli cell signaling by Desert hedgehog regulates the male germlineM J Bitgood
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Curr Biol 6:298-304. 1996..However, the molecular nature of these interactions is poorly understood. Desert hedgehog (Dhh) encodes a signaling molecule expressed in the testis, but not the ovary, and may therefore play a role in the regulation of spermatogenesis...
Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explantsE Marti
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 375:322-5. 1995..Moreover, antibodies that specifically recognize this peptide block induction of motor neurons by the notochord. We propose that Shh acts as a morphogen to induce distinct ventral cell types in the vertebrate central nervous system...
Distribution of Sonic hedgehog peptides in the developing chick and mouse embryoE Marti
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Development 121:2537-47. 1995..Thus, either long-range signaling is mediated indirectly by the activation of other signals, or alternatively the low levels of diffusing peptide are undetectable using available techniques...
Biochemical analysis of murine Wnt proteins reveals both shared and distinct propertiesL W Burrus
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Exp Cell Res 220:363-73. 1995..Whereas addition of suramin to COS cell cultures significantly increases the levels of all six Wnts in the medium, the addition of heparin only influences the levels of Wnt-1, Wnt-6, and Wnt-7b...
The classical mouse mutant postaxial hemimelia results from a mutation in the Wnt 7a geneB A Parr
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Dev Biol 202:228-34. 1998..Thus, the px mutation is predicted to be a likely null allele of the Wnt 7a gene. Our results provide another interesting example of a classical mutation that disrupts an important patterning gene in development...
A local Wnt-3a signal is required for development of the mammalian hippocampusS M Lee
Department of Molecular Biology, The Biolabs, Harvard University, Cambridge, MA 02138, USA
Development 127:457-67. 2000..Thus, Wnt-3a signaling is crucial for the normal growth of the hippocampus. We suggest that the coordination of growth with patterning may be a general role for Wnts during vertebrate development...
Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryoM J Bitgood
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Dev Biol 172:126-38. 1995..The frequent expression of Bmp-2, -4, and -6 in similar or adjacent cell populations suggests a conserved role for Hh/Bmp interactions in vertebrate development...
Proteolytic processing yields two secreted forms of sonic hedgehogD A Bumcrot
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138
Mol Cell Biol 15:2294-303. 1995..These results raise the possibility that amino- and carboxyl-terminal regions of Shh may have distinct functions in regulating cell-cell interactions in the vertebrate embryo...
Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limbB A Parr
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138
Nature 374:350-3. 1995..Many mutant mice also lack posterior digits, demonstrating that Wnt-7a is also required for anterior-posterior patterning. We propose that normal limb development requires interactions between the signalling systems for these two axes...
Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7aB A Parr
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 395:707-10. 1998..Therefore, we propose that signalling by Wnt-7a allows sexually dimorphic development of the Müllerian ducts...
Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tipsA Kispert
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Development 122:3627-37. 1996..We suggest that Wnt-11 acts as an autocrine factor within the ureter epithelium and that its expression is regulated at least in part by proteoglycans...
The effect of pertussis toxin on zebrafish development: a possible role for inhibitory G-proteins in hedgehog signalingM Hammerschmidt
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Dev Biol 194:166-71. 1998..Thus, GiPs may be involved in Hedgehog signaling in some, but not all target cells...
Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formationB St-Jacques
Harvard University, Department of Molecular and Cellular Biology, Cambridge, Massachusetts 02138 USA
Genes Dev 13:2072-86. 1999..Together, the results suggest a model in which Ihh coordinates diverse aspects of skeletal morphogenesis through PTHrP-dependent and independent processes...
Wnt-4 is a mesenchymal signal for epithelial transformation of metanephric mesenchyme in the developing kidneyA Kispert
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Development 125:4225-34. 1998....
Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferationF Long
Harvard University, Department of Molecular and Cellular Biology, Cambridge, MA 02138, USA
Development 128:5099-108. 2001..Taken together, the present study establishes Ihh as a key mitogen in the endochondral skeleton...
Female development in mammals is regulated by Wnt-4 signallingS Vainio
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 397:405-9. 1999..Wnt-4 may also be required for maintenance of the female germ line. Thus, the establishment of sexual dimorphism is under the control of both local and systemic signals...
More surprises in the Hedgehog signaling pathwayA P McMahon
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Cell 100:185-8. 2000
Abnormal hair development and apparent follicular transformation to mammary gland in the absence of hedgehog signalingAmel Gritli-Linde
Department of Oral Biochemistry, Sahlgrenska Academy at Goteborg University, Medicinaregatan 12F, Goteborg, Sweden
Dev Cell 12:99-112. 2007..Overall, our study uncovers a multifaceted function for Shh in sculpting and maintaining the integrity and identity of the developing HF...
Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes bone formationXiaolin Tu
Department of Medicine, Washington University Medical School, St Louis, MO 63110, USA
Dev Cell 12:113-27. 2007..Together, these results reveal a Wnt-dependent osteogenic mechanism, and they provide a potential target pathway for designing therapeutics to promote bone formation...
Control of transcription factor activity and osteoblast differentiation in mammalian cells using an evolved small-molecule-dependent inteinCourtney M Yuen
Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA
J Am Chem Soc 128:8939-46. 2006....
Independent regulation of skeletal growth by Ihh and IGF signalingFanxin Long
Department of Medicine, Washington University Medical School, St Louis, MO 63110, USA
Dev Biol 298:327-33. 2006..Here, we report that disruption of both IGF and Ihh signaling resulted in additive reduction in the size of the embryonic skeleton. Thus, IGF and Ihh signaling appear to control the growth of the skeleton in parallel pathways...
BMP signaling stimulates cellular differentiation at multiple steps during cartilage developmentTatsuya Kobayashi
Endocrine Unit, Massachusetts General Hospital, Boston, 02114, USA
Proc Natl Acad Sci U S A 102:18023-7. 2005..These results suggest that BMP signaling in prechondrogenic cells and in growth plate chondrocytes stimulates their chondrocytic differentiation and maturation toward hypertrophy, respectively...
A genome-wide RNA interference screen in Drosophila melanogaster cells for new components of the Hh signaling pathwayKent Nybakken
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
Nat Genet 37:1323-32. 2005..Finally, we showed that several of these genes have conserved roles in mammalian Hh signaling...
An ES cell system for rapid, spatial and temporal analysis of gene function in vitro and in vivoJunhao Mao
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Nucleic Acids Res 33:e155. 2005..This platform will facilitate rapid analysis of gene function in the mouse...
Noggin antagonism of BMP4 signaling controls development of the axial skeleton in the mouseMark Wijgerde
Department of Molecular and Cellular Biology, The Biolabs, 16 Divinity Avenue, Harvard University, Cambridge, MA 02138, USA
Dev Biol 286:149-57. 2005..Thus, specific interactions between Bmp4 and Noggin in the early embryo are critical for establishment and patterning of the somite and subsequent axial skeletal morphogenesis...
Neural crest origins of the neck and shoulderToshiyuki Matsuoka
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Nature 436:347-55. 2005..This has allowed us to trace the whereabouts of the cleithrum, the major shoulder bone of extinct land vertebrate ancestors, which seems to survive as the scapular spine in living mammals...
Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrPTatsuya Kobayashi
Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA
J Clin Invest 115:1734-42. 2005..These results demonstrate that Ihh acts on periarticular chondrocytes to stimulate their differentiation, thereby regulating the columnar cell mass independently of PTHrP...
Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney developmentAkio Kobayashi
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
Development 132:2809-23. 2005..We also demonstrate that the nephric duct is essential for the elongation and maintenance of the adjacent Mullerian duct, the anlage of the female reproductive tract...
Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterningSteven A Vokes
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Development 134:1977-89. 2007..Together, these approaches provide significant new insights into both tissue-specific and general transcriptional targets in a crucial Shh-mediated patterning process...
The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse developmentBenjamin L Allen
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Genes Dev 21:1244-57. 2007....
Wnt/beta-catenin signaling regulates nephron induction during mouse kidney developmentJoo Seop Park
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Development 134:2533-9. 2007..However, the failure of induced mesenchyme with high levels of beta-catenin activity to form epithelial structures suggests that modulating canonical signaling may be crucial for the cellular transition to the renal vesicle...
A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limbSteven A Vokes
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Genes Dev 22:2651-63. 2008..These studies provide the first comprehensive characterization of the transcriptional output of a Shh-patterning process in the mammalian embryo and a framework for elaborating regulatory networks in the developing limb...
Developmental biology. Grasping limb patterningClifford J Tabin
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Science 321:350-2. 2008
Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human diseaseCarl R Walkley
Department of Pediatric Oncology, Dana Farber Cancer Institute, Division of Hematology Oncology, Boston, MA 02115, USA
Genes Dev 22:1662-76. 2008..Due to the strong similarity between murine osteosarcoma and human osteosarcoma in this model, this should provide a valuable platform for addressing the molecular genetics of osteosarcoma and for developing novel therapeutic strategies...
In vivo targeted deletion of calpain small subunit, Capn4, in cells of the osteoblast lineage impairs cell proliferation, differentiation, and bone formationMasako Shimada
Endocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA
J Biol Chem 283:21002-10. 2008..Collectively, our findings provide the first in vivo demonstration that the calpain small subunit is essential for proper osteoblast activity and bone remodeling...
Hoxd11 specifies a program of metanephric kidney development within the intermediate mesoderm of the mouse embryoJoshua W Mugford
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Dev Biol 319:396-405. 2008..This program maintains tubule forming progenitors and instructs a metanephric specific pattern of nephron differentiation...
Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchymeJayaraj Rajagopal
Department of Molecular and Cellular Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA
Development 135:1625-34. 2008..Together, these cascades result in the coordinated proliferation of adjacent epithelial and mesenchymal cells to stimulate organ growth with few alterations in differentiation and patterning...
Indian hedgehog signaling from endothelial cells is required for sclera and retinal pigment epithelium development in the mouse eyeGabriel D Dakubo
University of Ottawa Eye Institute, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5
Dev Biol 320:242-55. 2008..This study identifies Ihh as a novel choroid-derived signal that regulates RPE, sclera and neural retina development...
Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterningChester E Chamberlain
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Development 135:1097-106. 2008..This study, in which we directly observe, measure, localize and modify notochord-derived Shh ligand in the context of neural patterning, provides several new insights into mechanisms of Shh morphogen action...
Dicer-dependent pathways regulate chondrocyte proliferation and differentiationTatsuya Kobayashi
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Proc Natl Acad Sci U S A 105:1949-54. 2008..Our results demonstrate the critical role of the Dicer-dependent pathway in the regulation of chondrocyte proliferation and differentiation during skeletal development...
The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephrosRebecca A Wingert
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
PLoS Genet 3:1922-38. 2007..These findings reveal a novel link between the RA and cdx pathways and provide a model for how pronephric nephrons are segmented and positioned along the embryonic axis...
Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2Wenlai Zhou
Howard Hughes Medical Institute and Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
Nat Genet 39:1225-34. 2007..Thus, we propose that transcriptional readout mediated at least in part by a Wnt11 --> ATF/CREB --> TGFbeta2 pathway is critical in regulating morphogenesis in response to noncanonical Wnt signaling...
Regulation of skeletogenic differentiation in cranial dermal boneArhat Abzhanov
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Development 134:3133-44. 2007..These results provide a framework for understanding dermal bone development with an aim of bringing it closer to the molecular and cellular resolution available for the endochondral bone development...
Fate-mapping of the epithelial seam during palatal fusion rules out epithelial-mesenchymal transformationForugh Vaziri Sani
Department of Oral Biochemistry, Sahlgrenska Academy at Goteborg University, Medicinaregatan 12F, SE 405 30 Goteborg, Sweden
Dev Biol 285:490-5. 2005..Our analyses provide conclusive evidence that rules out the occurrence of epithelial-mesenchymal transformation of MES cells...
Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiationDonald A Glass
Department of Molecular and Human Genetics, Bone Disease Program of Texas, Houston, 77030, USA
Dev Cell 8:751-64. 2005....
Retinal ganglion cell-derived sonic hedgehog signaling is required for optic disc and stalk neuroepithelial cell developmentGabriel D Dakubo
Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada
Development 130:2967-80. 2003..Together, these data provide a novel insight into the source of Hh that promotes neuroepithelial cell development in the mammalian optic disc and stalk...
Loss of Emx2 function leads to ectopic expression of Wnt1 in the developing telencephalon and cortical dysplasiaKeith L Ligon
Department of Pediatric Oncology, Dana Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 0215, USA
Development 130:2275-87. 2003..They further suggest that EMX2-Wnt1 interactions are essential for normal development of preplate derivatives in the mammalian cerebral cortex...
Efficient gene modulation in mouse epiblast using a Sox2Cre transgenic mouse strainShigemi Hayashi
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Gene Expr Patterns 2:93-7. 2002....
Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lungPao Tien Chuang
Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
Genes Dev 17:342-7. 2003..Our studies focused on Hip1 in the lung. Here, a dynamic interaction between Hh and fibroblast growth factor (Fgf) signaling, modulated at least in part by Hip1, controls early lung branching...
A direct requirement for Hedgehog signaling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cordMark Wijgerde
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, Cambridge, Massachusetts 02138, USA
Genes Dev 16:2849-64. 2002..Thus, Hh signaling is essential for organizing ventral cell pattern, possibly through the control of differential cell affinities...
Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarizationAmel Gritli-Linde
Department of Oral Biochemistry, Sahlgrenska Academy at Goteborg University, Sweden
Development 129:5323-37. 2002..Furthermore, we provide evidence that Shh signaling between ameloblasts and the overlying stratum intermedium may involve subcellular localization of Patched 2 and Gli1 mRNAs, both of which are targets of Shh signaling in these cells...
Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidneyJing Yu
Department of Molecular and Cellular Biology, 16 Divinity Avenue, Harvard University, Cambridge MA 02138, USA
Development 129:5301-12. 2002....
Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and Hedgehog signalingMurielle Rallu
Developmental Genetics Program and the Department of Cell Biology, The Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York 10016, USA
Development 129:4963-74. 2002..In addition these results support the idea that, in addition to hedgehog signaling, a Shh-independent pathways must act during development to pattern the telencephalon...
A sonic hedgehog-dependent signaling relay regulates growth of diencephalic and mesencephalic primordia in the early mouse embryoMakoto Ishibashi
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Development 129:4807-19. 2002....
Development of normal retinal organization depends on Sonic hedgehog signaling from ganglion cellsYa Ping Wang
Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada
Nat Neurosci 5:831-2. 2002..Here we show that Sonic hedgehog signaling from RGCs is required for the normal laminar organization in the vertebrate retina...
Transient expression of the bHLH factor neurogenin-2 marks a subpopulation of neural crest cells biased for a sensory but not a neuronal fateMariela Zirlinger
Division of Biology 216 76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 99:8084-9. 2002..Taken together with previous work, these data suggest that NCCs become restricted to sensory or autonomic sublineages before becoming committed to neuronal or glial fates...
A mitogen gradient of dorsal midline Wnts organizes growth in the CNSSean G Megason
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Development 129:2087-98. 2002..Computer modeling demonstrates this model is a robust and self-regulating mechanism for patterning cell cycle regulation in a growing tissue. Supplemental data available on-line..
Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney developmentArindam Majumdar
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Development 130:3175-85. 2003....
Combined activities of hedgehog signaling inhibitors regulate pancreas developmentHiroshi Kawahira
Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA
Development 130:4871-9. 2003..Reduction of Fgf10 expression in Hhip homozygous mutants suggests that at least some of the observed phenotypes result from hedgehog-mediated inhibition of Fgf signaling at early stages...
Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell nichesRobert Machold
Developmental Genetics Program and Department of Cell Biology, The Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA
Neuron 39:937-50. 2003..These results suggest that hedgehog signaling is required to maintain progenitor cells in the postnatal telencephalon...
Mouse brain organization revealed through direct genome-scale TF expression analysisPaul A Gray
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
Science 306:2255-7. 2004..We provide a comprehensive inventory of murine TFs and their expression patterns in a searchable brain atlas database...
Mouse Disp1 is required in sonic hedgehog-expressing cells for paracrine activity of the cholesterol-modified ligandHua Tian
One DNA Way, Genentech Incorporated, South San Francisco, CA 94080, USA
Development 132:133-42. 2005..In both respects, Disp function is conserved from Drosophila to mice...
Growth and pattern of the mammalian neural tube are governed by partially overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1Juhee Jeong
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Development 132:143-54. 2005..Furthermore, this feedback mechanism is crucial in generating a neural tube that contains appropriate numbers of all ventral and intermediate neuronal cell types...
Hedgehog signaling: iguana debuts as a nuclear gatekeeperSteven A Vokes
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Curr Biol 14:R668-70. 2004..Iguana appears to play a role in regulating this process independently of Hedgehog signaling...
Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identitiesBrian D Harfe
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, FL 32610, USA
Cell 118:517-28. 2004..Genetic studies of the effects of limiting accessibility of Shh within the limb support this model, in which the effect of the Shh morphogen is dictated by a temporal as well as a spatial gradient...
Research Grants
- PATTERN REGULATION IN THE VERTEBRATE CNSAndrew McMahon; Fiscal Year: 2002....
- CELL INTERACTIONS IN DEVELOPMENT OF THE MAMMALIAN KIDNEYAndrew McMahon; Fiscal Year: 2002..Finally, given the importance of Wnt-signals, they will start to examine their receptors in the kidney. ..
- REGULATION OF CNS AND LIMB POLARITY BY SONIC HEDGEHOGAndrew McMahon; Fiscal Year: 2004..Aim 3 proposes to adopt this strategy to address Shh action in the limb and specific regions of the developing CNS, where its role cannot be assessed with existing null mutations. ..
- REGULATION OF CNS AND LIMB POLARITY BY SONIC HEDGEHOGAndrew McMahon; Fiscal Year: 2007..Aim 3 will explore the roles of several novel targets of HH-signaling identified in transcriptional screens. Aim 4 proposes to characterize a new inducible model of HH-mediated tumorigenesis. ..
- CELL INTERACTIONS IN DEVELOPMENT OF THE MAMMALIAN KIDNEYAndrew McMahon; Fiscal Year: 2007..abstract_text> ..
- Kidney molecular atlas projectAndrew McMahon; Fiscal Year: 2007..Aim 4: We will use BAC-mediated transgenics to express fluorescent reporter proteins and Cre recombinase in specific cell populations for cell marking, cell fate and genetic manipulation studies. ..
- CORE--GENE EXPRESSIONAndrew McMahon; Fiscal Year: 2007..Further, we will perform a rapid analysis of large data sets emerging from transcriptional profiling approaches addressing underlying molecular mechanisms of skeletogenesis. ..
- REGULATION OF CNS AND LIMB POLARITY BY SONIC HEDGEHOGAndrew McMahon; Fiscal Year: 1999..Collectively, these experiments will shed light on the synthesis, secretion and mechanism of action of Shh in vertebrate development. ..
