Gene Symbol: Msx2
Description: msh homeobox 2
Alias: BB122635, Hox-8, Hox8, Hox8.1, homeobox protein MSX-2, homeo box, msh-like 2, homeobox protein Hox-8-1, homeobox, msh-like 2
Species: mouse
Products:     Msx2

Top Publications

  1. Song L, Li Y, Wang K, Wang Y, Molotkov A, Gao L, et al. Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion. Development. 2009;136:3161-71 pubmed publisher
    ..The expression of the homeobox genes Msx1 and Msx2 is dramatically reduced in the mutants, which prevents the outgrowth of orofacial primordia, especially in the ..
  2. Zhang Z, Zhang X, Avniel W, Song Y, Jones S, Jones T, et al. Malleal processus brevis is dispensable for normal hearing in mice. Dev Dyn. 2003;227:69-77 pubmed
    ..Here, we show that the expression of Msx1 and Msx2 overlaps in the malleal primordium during early embryonic development...
  3. Sun X, Mariani F, Martin G. Functions of FGF signalling from the apical ectodermal ridge in limb development. Nature. 2002;418:501-8 pubmed
    ..In the complete absence of both FGF4 and FGF8 activities, limb development fails. We present a model to explain how the mutant phenotypes arise from FGF-mediated effects on limb bud size and cell survival. ..
  4. Goupille O, Saint Cloment C, Lopes M, Montarras D, Robert B. Msx1 and Msx2 are expressed in sub-populations of vascular smooth muscle cells. Dev Dyn. 2008;237:2187-94 pubmed publisher
    Using an nlacZ reporter gene inserted at the Msx1 and Msx2 loci, we could analyze the expression of these homeogenes in the adult mouse. We observed that Msx genes are prominently expressed in a subset of blood vessels...
  5. Gunther T, Struwe M, Aguzzi A, Schughart K. Open brain, a new mouse mutant with severe neural tube defects, shows altered gene expression patterns in the developing spinal cord. Development. 1994;120:3119-30 pubmed
    ..The implications of these findings are discussed in the context of dorsoventral patterning of the developing neural tube and compared with known mouse mutants exhibiting similar defects. ..
  6. Vainio S, Karavanova I, Jowett A, Thesleff I. Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell. 1993;75:45-58 pubmed
    ..In addition, BMP-4 induced its own mesenchymal expression. These findings support the hypothesis that BMP-4 mediates epithelial-mesenchymal interactions during early tooth development. ..
  7. Maatouk D, Choi K, Bouldin C, Harfe B. In the limb AER Bmp2 and Bmp4 are required for dorsal-ventral patterning and interdigital cell death but not limb outgrowth. Dev Biol. 2009;327:516-23 pubmed publisher
    ..Our data suggests that AER expression of Bmp2 and Bmp4 is required for digit and dorsal-ventral patterning but surprisingly not for limb outgrowth...
  8. Bosman E, Lawson K, Debruyn J, Beek L, Francis A, Schoonjans L, et al. Smad5 determines murine amnion fate through the control of bone morphogenetic protein expression and signalling levels. Development. 2006;133:3399-409 pubmed
    ..These results support a model in which loss of Smad5 results paradoxically in gain of Bmp function defects in the amnion. ..
  9. Seo S, Kume T. Forkhead transcription factors, Foxc1 and Foxc2, are required for the morphogenesis of the cardiac outflow tract. Dev Biol. 2006;296:421-36 pubmed
    ..Taken together, our results demonstrate that Foxc1 and Foxc2 play pivotal roles in the early processes of heart development, especially acting upstream of the Tbx1-FGF cascade during the morphogenesis of the OFT. ..

More Information


  1. Ybot Gonzalez P, Gaston Massuet C, Girdler G, Klingensmith J, Arkell R, Greene N, et al. Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling. Development. 2007;134:3203-11 pubmed
    ..Our findings reveal a molecular mechanism based on antagonism of Bmp signalling that underlies the regulation of DLHP formation during mouse spinal neural tube closure. ..
  2. Michos O, Panman L, Vintersten K, Beier K, Zeller R, Zuniga A. Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis. Development. 2004;131:3401-10 pubmed
    ..As a consequence, the metanephric mesenchyme is eliminated by apoptosis, in the same way as the core mesenchymal cells of the limb bud. ..
  3. Ishii M, Han J, Yen H, Sucov H, Chai Y, Maxson R. Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest. Development. 2005;132:4937-50 pubmed
    ..Here, we focus on the function of Msx1 and Msx2, homeobox genes implicated in several disorders affecting craniofacial development in humans...
  4. Houzelstein D, Cohen A, Buckingham M, Robert B. Insertional mutation of the mouse Msx1 homeobox gene by an nlacZ reporter gene. Mech Dev. 1997;65:123-33 pubmed
    ..the reason for this limited phenotype, we compared the pattern of Msx1 expression with that of the closely related Msx2 gene in wild type embryos and in Msx1-/- mutants...
  5. Bell S, Schreiner C, Scott W. The loss of ventral ectoderm identity correlates with the inability to form an AER in the legless hindlimb bud. Mech Dev. 1998;74:41-50 pubmed
    ..These data suggest that establishment of a dorso-ventral ectodermal interface is not sufficient for AER formation and that restriction of lmx-1b to the dorsal mesenchyme is coordinately linked to AER formation. ..
  6. Lallemand Y, Nicola M, Ramos C, Bach A, Cloment C, Robert B. Analysis of Msx1; Msx2 double mutants reveals multiple roles for Msx genes in limb development. Development. 2005;132:3003-14 pubmed
    The homeobox-containing genes Msx1 and Msx2 are highly expressed in the limb field from the earliest stages of limb formation and, subsequently, in both the apical ectodermal ridge and underlying mesenchyme...
  7. Liu F, Chu E, WATT B, Zhang Y, Gallant N, Andl T, et al. Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev Biol. 2008;313:210-24 pubmed
    ..Conversely, expression of key morphogenetic regulators including Bmp4, Msx1, and Msx2 is downregulated in embryos expressing the secreted Wnt inhibitor Dkk1 which blocks signaling in epithelial and ..
  8. Robledo R, Rajan L, Li X, Lufkin T. The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev. 2002;16:1089-101 pubmed
    ..Furthermore, spatiotemporal-specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of Dlx5/6 null mice can fully rescue Dlx/Dll function in limb outgrowth. ..
  9. Li C, Xu X, Nelson D, Williams T, Kuehn M, Deng C. FGFR1 function at the earliest stages of mouse limb development plays an indispensable role in subsequent autopod morphogenesis. Development. 2005;132:4755-64 pubmed
  10. Dunn N, Winnier G, Hargett L, Schrick J, Fogo A, Hogan B. Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol. 1997;188:235-47 pubmed
    ..These genetic interactions suggest a model for the multigenic control of anterior digit patterning during vertebrate limb development. ..
  11. Lewandoski M, Sun X, Martin G. Fgf8 signalling from the AER is essential for normal limb development. Nat Genet. 2000;26:460-3 pubmed
    ..Our data identify Fgf8 as the only known AER-Fgf individually necessary for normal limb development, and provide insight into the function of Fgf signalling from the AER in the normal outgrowth and patterning of the limb. ..
  12. Abdelwahid E, Rice D, Pelliniemi L, Jokinen E. Overlapping and differential localization of Bmp-2, Bmp-4, Msx-2 and apoptosis in the endocardial cushion and adjacent tissues of the developing mouse heart. Cell Tissue Res. 2001;305:67-78 pubmed
    ..In addition, BMP-2, BMP-4 and MSX-2 and apoptosis seem to be associated with differentiation of the endocardial cushion. ..
  13. Lakkis M, Epstein J. Neurofibromin modulation of ras activity is required for normal endocardial-mesenchymal transformation in the developing heart. Development. 1998;125:4359-67 pubmed
    ..These results indicate that neurofibromin normally acts to modulate epithelial-mesenchymal transformation and proliferation in the developing heart by down regulating ras activity. ..
  14. Rice R, Rice D, Olsen B, Thesleff I. Progression of calvarial bone development requires Foxc1 regulation of Msx2 and Alx4. Dev Biol. 2003;262:75-87 pubmed
    ..ossification defect in ch mutants to the calvarial mesenchyme, which lacks the expression of transcription factors Msx2 and Alx4. This lack of expression is associated with a reduction in the proliferation of osteoprogenitor cells...
  15. Grotewold L, Ruther U. The Wnt antagonist Dickkopf-1 is regulated by Bmp signaling and c-Jun and modulates programmed cell death. EMBO J. 2002;21:966-75 pubmed
    ..Taken together, our results provide evidence for an important role of Dkk-1-mediated inhibition of Wnt/beta-catenin signaling in response to different stress signals that all converge on the activation of c-Jun in vivo. ..
  16. Wang C, Omi M, Ferrari D, Cheng H, Lizarraga G, Chin H, et al. Function of BMPs in the apical ectoderm of the developing mouse limb. Dev Biol. 2004;269:109-22 pubmed
    ..To study the functions of apical ectodermal BMPs, an AER-specific promoter element from the Msx2 gene was used to target expression of the potent BMP antagonist noggin to the apical ectoderm of the limbs of ..
  17. Marijanovic I, Kronenberg M, Erceg Ivkosić I, Lichtler A. Comparison of proliferation and differentiation of calvarial osteoblast cultures derived from Msx2 deficient and wild type mice. Coll Antropol. 2009;33:919-24 pubmed
    We analyzed proliferation and differentiation of calvarial osteoblasts derived from Msx2 deficient in comparison with wild type mice...
  18. Hosokawa R, Urata M, Han J, Zehnaly A, Bringas P, Nonaka K, et al. TGF-beta mediated Msx2 expression controls occipital somites-derived caudal region of skull development. Dev Biol. 2007;310:140-53 pubmed
    ..Expression of Msx2, a critical factor in the formation of the dorsoventral axis, is diminished in the Tgfbr2 mutant...
  19. Yang Y, Klingensmith J. Roles of organizer factors and BMP antagonism in mammalian forebrain establishment. Dev Biol. 2006;296:458-75 pubmed
    ..These results lead to a model in which BMP antagonism supplied by exogenous tissues promotes forebrain establishment and maintenance in the murine ectoderm. ..
  20. Cobb J, Duboule D. Comparative analysis of genes downstream of the Hoxd cluster in developing digits and external genitalia. Development. 2005;132:3055-67 pubmed
    ..e. the digits and the penis/clitoris. ..
  21. Chizhikov V, Lindgren A, Currle D, Rose M, Monuki E, Millen K. The roof plate regulates cerebellar cell-type specification and proliferation. Development. 2006;133:2793-804 pubmed
    ..Thus, in addition to the isthmus, the roof plate represents an important signaling center controlling multiple aspects of cerebellar patterning. ..
  22. Hussein S, Duff E, Sirard C. Smad4 and beta-catenin co-activators functionally interact with lymphoid-enhancing factor to regulate graded expression of Msx2. J Biol Chem. 2003;278:48805-14 pubmed
    ..Here we show in murine embryonic stem cells that BMP-dependent activation of Msx2 is mediated via the cooperative binding of Smad4 at two Smad binding elements and of lymphoid enhancing factor (..
  23. Liu W, Selever J, Murali D, Sun X, Brugger S, Ma L, et al. Threshold-specific requirements for Bmp4 in mandibular development. Dev Biol. 2005;283:282-93 pubmed
    ..Furthermore, our data uncovered different Bmp4 thresholds for expression of the Bmp-dependent Msx1 and Msx2 genes in mandibular mesenchyme...
  24. Talamillo A, Delgado I, Nakamura T, de Vega S, Yoshitomi Y, Unda F, et al. Role of Epiprofin, a zinc-finger transcription factor, in limb development. Dev Biol. 2010;337:363-74 pubmed publisher
  25. Han J, Ishii M, Bringas P, Maas R, Maxson R, Chai Y. Concerted action of Msx1 and Msx2 in regulating cranial neural crest cell differentiation during frontal bone development. Mech Dev. 2007;124:729-45 pubmed
    The homeobox genes Msx1 and Msx2 function as transcriptional regulators that control cellular proliferation and differentiation during embryonic development...
  26. Jernvall J, Aberg T, Kettunen P, Keranen S, Thesleff I. The life history of an embryonic signaling center: BMP-4 induces p21 and is associated with apoptosis in the mouse tooth enamel knot. Development. 1998;125:161-9 pubmed
    ..These results show that the life history of the enamel knot is intimately linked to the initiation of tooth shape development and support the role of the enamel knot as an embryonic signaling center. ..
  27. Liu Y, Tang Z, Kundu R, Wu L, Luo W, Zhu D, et al. Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for MSX2-mediated craniosynostosis in humans. Dev Biol. 1999;205:260-74 pubmed
    ..We found previously that a single amino acid substitution in the homeodomain of the human MSX2 gene is associated with the autosomal dominant disorder craniosynostosis, Boston type...
  28. Ahn K, Mishina Y, Hanks M, Behringer R, Crenshaw E. BMPR-IA signaling is required for the formation of the apical ectodermal ridge and dorsal-ventral patterning of the limb. Development. 2001;128:4449-61 pubmed
    ..This study demonstrates that BMPR-IA signaling plays a crucial role in AER formation and in the establishment of the dorsal/ventral patterning during limb development. ..
  29. Bensoussan V, Lallemand Y, Moreau J, Cloment C, Langa F, Robert B. Generation of an Msx2-GFP conditional null allele. Genesis. 2008;46:276-82 pubmed publisher
    Msx1 and Msx2, two members of the Msx gene family, encode homeoprotein transcription factors and play critical roles during mouse development...
  30. Bach A, Lallemand Y, Nicola M, Ramos C, Mathis L, Maufras M, et al. Msx1 is required for dorsal diencephalon patterning. Development. 2003;130:4025-36 pubmed
    ..In double Msx1/Msx2 mutants, Wnt1 expression is completely abolished at the dorsal midline of the diencephalon and rostral ..
  31. Dudas M, Kim J, Li W, Nagy A, Larsson J, Karlsson S, et al. Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during facial morphogenesis and palatal fusion. Dev Biol. 2006;296:298-314 pubmed
  32. Jabs E, Muller U, Li X, Ma L, Luo W, Haworth I, et al. A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis. Cell. 1993;75:443-50 pubmed
    ..The locus for one autosomal dominant form of craniosynostosis has been mapped to chromosome 5qter. The human MSX2 gene localizes to chromosome 5, and a polymorphic marker in the MSX2 intron segregates in a kindred with the ..
  33. Pfaff S, Mendelsohn M, Stewart C, Edlund T, Jessell T. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Cell. 1996;84:309-20 pubmed
    ..These results show that ISL1 is required for the generation of motor neurons and suggest that motor neuron generation is required for the subsequent differentiation of certain interneurons. ..
  34. Bensoussan Trigano V, Lallemand Y, Saint Cloment C, Robert B. Msx1 and Msx2 in limb mesenchyme modulate digit number and identity. Dev Dyn. 2011;240:1190-202 pubmed publisher
    Msx1 and Msx2 encode homeodomain transcription factors that play a crucial role in limb development...
  35. Hollnagel A, Oehlmann V, Heymer J, Ruther U, Nordheim A. Id genes are direct targets of bone morphogenetic protein induction in embryonic stem cells. J Biol Chem. 1999;274:19838-45 pubmed
    ..We therefore propose that the Msx and Id genes are direct target genes of embryonic BMP4 signaling in vivo. ..
  36. Chiang C, Litingtung Y, Harris M, Simandl B, Li Y, Beachy P, et al. Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Dev Biol. 2001;236:421-35 pubmed
    ..According to this model, the limb bud signaling centers, including the zone of polarizing activity (ZPA) acting through Shh, are required to elaborate upon the axial information provided by the native limb field prepattern. ..
  37. Ishii M, Merrill A, Chan Y, Gitelman I, Rice D, Sucov H, et al. Msx2 and Twist cooperatively control the development of the neural crest-derived skeletogenic mesenchyme of the murine skull vault. Development. 2003;130:6131-42 pubmed
    ..One such anomaly is familial calvarial foramina, persistent unossified areas within the skull vault. Mutations in MSX2 and TWIST are known to cause calvarial foramina in humans...
  38. Depew M, Lufkin T, Rubenstein J. Specification of jaw subdivisions by Dlx genes. Science. 2002;298:381-5 pubmed
    ..We suggest that nested Dlx expression in the arches patterns their proximodistal axes. Evolutionary acquisition and subsequent refinement of jaws may have been dependent on modification of Dlx expression. ..
  39. Pajni Underwood S, Wilson C, Elder C, Mishina Y, Lewandoski M. BMP signals control limb bud interdigital programmed cell death by regulating FGF signaling. Development. 2007;134:2359-68 pubmed
    ..We conclude that during normal embryogenesis, BMP signaling to the AER indirectly regulates interdigit PCD by regulating AER-FGFs, which act as survival factors for the interdigit mesenchyme. ..
  40. Morgan E, Nguyen S, Scott V, Stadler H. Loss of Bmp7 and Fgf8 signaling in Hoxa13-mutant mice causes hypospadia. Development. 2003;130:3095-109 pubmed
    ..Finally, a novel role for Hoxa13 in the vascularization of the glans penis is also identified. ..
  41. Khokha M, Hsu D, Brunet L, Dionne M, Harland R. Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning. Nat Genet. 2003;34:303-7 pubmed
    ..Although Bmps and their antagonists have multiple roles in limb development, these experiments show that gremlin is the principal BMP antagonist required for early limb outgrowth and patterning. ..
  42. Vivatbutsiri P, Ichinose S, Hytönen M, Sainio K, Eto K, Iseki S. Impaired meningeal development in association with apical expansion of calvarial bone osteogenesis in the Foxc1 mutant. J Anat. 2008;212:603-11 pubmed publisher
    ..These results suggest that there is a close association between meningeal development and the apical growth of the skull bones. ..
  43. Aïoub M, Lezot F, Molla M, Castaneda B, Robert B, Goubin G, et al. Msx2 -/- transgenic mice develop compound amelogenesis imperfecta, dentinogenesis imperfecta and periodental osteopetrosis. Bone. 2007;41:851-9 pubmed
    The physiological function of the transcription factor Msx2 in tooth and alveolar bone was analysed using a knock-in transgenic mouse line...
  44. Matsubara T, Kida K, Yamaguchi A, Hata K, Ichida F, Meguro H, et al. BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation. J Biol Chem. 2008;283:29119-25 pubmed publisher
    ..Moreover, overexpression of a homeobox gene, Msx2, which is up-regulated by BMP2 and promotes osteoblastic differentiation, induced Osterix expression in the Runx2-..
  45. Lallemand Y, Bensoussan V, Cloment C, Robert B. Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb. Dev Biol. 2009;331:189-98 pubmed publisher
    ..In this report, we show that Msx1 and Msx2 are targets and downstream effectors of Gli3R...
  46. Choi K, Lee C, Maatouk D, Harfe B. Bmp2, Bmp4 and Bmp7 are co-required in the mouse AER for normal digit patterning but not limb outgrowth. PLoS ONE. 2012;7:e37826 pubmed publisher
    ..Bmp ligands, Bmp2, Bmp4 and Bmp7 from the AER of the limb bud using floxed conditional alleles and the Msx2-cre allele. Surprisingly, only defects in digit patterning and not limb outgrowth were observed...
  47. Selever J, Liu W, Lu M, Behringer R, Martin J. Bmp4 in limb bud mesoderm regulates digit pattern by controlling AER development. Dev Biol. 2004;276:268-79 pubmed
    ..Our data show that Bmp4 in limb mesoderm regulates AER induction and maturation and implicate signaling from the AER in regulation of digit number and identity. ..
  48. Eggenschwiler J, Anderson K. Dorsal and lateral fates in the mouse neural tube require the cell-autonomous activity of the open brain gene. Dev Biol. 2000;227:648-60 pubmed
    ..The data indicate that opb(+) could act as either a novel component of a dorsalizing pathway or a novel intracellular negative regulator of the Shh signal transduction pathway. ..
  49. Wu L, Li M, Hinton D, Guo L, Jiang S, Wang J, et al. Microphthalmia resulting from MSX2-induced apoptosis in the optic vesicle. Invest Ophthalmol Vis Sci. 2003;44:2404-12 pubmed
    ..Msx genes have been shown to be expressed in the developing eye. In the Msx1;Msx2, double mutant mouse, eye development arrests early in embryogenesis...
  50. Mackenzie A, Ferguson M, Sharpe P. Expression patterns of the homeobox gene, Hox-8, in the mouse embryo suggest a role in specifying tooth initiation and shape. Development. 1992;115:403-20 pubmed
    ..This reciprocity of expression suggests an interactive role between Hox-7, Hox-8 and other genes in regulating epithelial mesenchymal interactions during dental differentiation.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  51. Ichida F, Nishimura R, Hata K, Matsubara T, Ikeda F, Hisada K, et al. Reciprocal roles of MSX2 in regulation of osteoblast and adipocyte differentiation. J Biol Chem. 2004;279:34015-22 pubmed
    Mice deficient in the Msx2 gene manifest defects in skull ossification and a marked reduction in bone formation associated with decreases in osteoblast numbers, thus suggesting that Msx2 is involved in bone formation...
  52. Bell S, Schreiner C, Waclaw R, Campbell K, Potter S, Scott W. Sp8 is crucial for limb outgrowth and neuropore closure. Proc Natl Acad Sci U S A. 2003;100:12195-200 pubmed
    ..These observations indicate that Sp8 functions downstream of Wnt3, Fgf10, and Bmpr1a in the signaling cascade that mediates AER formation. ..
  53. Han M, Yang X, Farrington J, Muneoka K. Digit regeneration is regulated by Msx1 and BMP4 in fetal mice. Development. 2003;130:5123-32 pubmed
    ..5) digit, we now show that digit tip regeneration occurs in organ culture and that Msx1, but not Msx2, mutant mice display a regeneration defect...
  54. Fu H, Ishii M, Gu Y, Maxson R. Conditional alleles of Msx1 and Msx2. Genesis. 2007;45:477-81 pubmed
    The msh-related homeobox genes, Msx1 and Msx2, have a variety functions during murine organogenesis, Msx1 in the development of the palate and teeth, Msx2 in the skull, teeth, and skin. Msx1 mutants die perinatally...
  55. Brugger S, Merrill A, Torres Vazquez J, Wu N, Ting M, Cho J, et al. A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos. Development. 2004;131:5153-65 pubmed
    ..Here, we identify a BMP-responsive enhancer of Msx2, an immediate early target of bone morphogenetic protein (BMP) signaling...
  56. Ohkubo Y, Chiang C, Rubenstein J. Coordinate regulation and synergistic actions of BMP4, SHH and FGF8 in the rostral prosencephalon regulate morphogenesis of the telencephalic and optic vesicles. Neuroscience. 2002;111:1-17 pubmed
  57. Molla M, Descroix V, Aïoub M, Simon S, Castaneda B, Hotton D, et al. Enamel protein regulation and dental and periodontal physiopathology in MSX2 mutant mice. Am J Pathol. 2010;177:2516-26 pubmed publisher
    ..This study analyzed the MSX2 protein during mouse postnatal growth as well as in the adult...
  58. Dassule H, Lewis P, Bei M, Maas R, McMahon A. Sonic hedgehog regulates growth and morphogenesis of the tooth. Development. 2000;127:4775-85 pubmed
    ..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. ..
  59. Bendall A, Abate Shen C. Roles for Msx and Dlx homeoproteins in vertebrate development. Gene. 2000;247:17-31 pubmed
    ..Moreover, their ability to oppose each other's transcriptional actions implies a mechanism underlying their complementary or antagonistic functions during development. ..
  60. Delgado I, Dominguez Frutos E, Schimmang T, Ros M. The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP-mediated cell death. Dev Dyn. 2008;237:649-58 pubmed publisher
    ..These limbs also exhibit an abnormal area of cell death at the anterior forelimb autopod, overlapping with an ectopic domain of Bmp7 expression, which can explain the abnormal morphogenesis of the anterior autopod. ..
  61. Satokata I, Ma L, Ohshima H, Bei M, Woo I, Nishizawa K, et al. Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nat Genet. 2000;24:391-5 pubmed
    ..Enhanced DNA binding by a mutant MSX2 homeodomain results in a gain of function and produces craniosynostosis in humans...
  62. Mills A, Zheng B, Wang X, Vogel H, Roop D, Bradley A. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature. 1999;398:708-13 pubmed
    ..Thus, in contrast to p53, p63 is essential for several aspects of ectodermal differentiation during embryogenesis...
  63. Lopes M, Goupille O, Saint Cloment C, Lallemand Y, Cumano A, Robert B. Msx genes define a population of mural cell precursors required for head blood vessel maturation. Development. 2011;138:3055-66 pubmed publisher
    ..We previously showed that, in the mouse embryo, Msx1(lacZ) and Msx2(lacZ) are expressed in mural cells and in a few endothelial cells...
  64. Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen M, et al. Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism. Mol Cell Biol. 1997;17:2920-32 pubmed
    ..Finally, we show that the expression patterns of representative Msx and Dlx genes (Msx1, Msx2, Dlx2, and Dlx5) overlap in mouse embryogenesis during limb bud and craniofacial development, consistent with the ..
  65. Wang W, Chen X, Xu H, Lufkin T. Msx3: a novel murine homologue of the Drosophila msh homeobox gene restricted to the dorsal embryonic central nervous system. Mech Dev. 1996;58:203-15 pubmed
    ..Msx3 maps to the distal end of mouse chromosome 7, thus it is unlinked to either Msx1 or Msx2. RNA in situ analysis of Msx3 gene expression during early development revealed that it is restricted to the dorsal ..
  66. Bulgakov O, Eggenschwiler J, Hong D, Anderson K, Li T. FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues. Development. 2004;131:2149-59 pubmed
    ..Although it is expressed broadly, FKBP8 is required to antagonize SHH signaling primarily in neural tissues, suggesting that hedgehog signal transduction is subject to cell-type specific modulation during mammalian development. ..
  67. Bénazet J, Bischofberger M, Tiecke E, Gonçalves A, Martin J, Zuniga A, et al. A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning. Science. 2009;323:1050-3 pubmed publisher
    ..This self-regulatory signaling network results in robust regulation of distal limb development that is able to compensate for variations by interconnectivity among the three signaling pathways. ..
  68. Chen Y, Ishii M, Sun J, Sucov H, Maxson R. Msx1 and Msx2 regulate survival of secondary heart field precursors and post-migratory proliferation of cardiac neural crest in the outflow tract. Dev Biol. 2007;308:421-37 pubmed
    Msx1 and Msx2 are highly conserved, Nk-related homeodomain transcription factors that are essential for a variety of tissue-tissue interactions during vertebrate organogenesis...
  69. Bandyopadhyay A, Tsuji K, Cox K, Harfe B, Rosen V, Tabin C. Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS Genet. 2006;2:e216 pubmed
    ..In contrast, we find that the loss of both BMP2 and BMP4 results in a severe impairment of osteogenesis. ..
  70. Ma L, Lu M, Schwartz R, Martin J. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development. 2005;132:5601-11 pubmed
    ..helix-loop-helix factor Twist1, previously implicated in EMT in cancer metastases, and the homeobox genes Msx1 and Msx2. Deletion of the Bmp type 1A receptor, Bmpr1a, in endocardium also resulted in failed cushion formation, indicating ..
  71. Lu P, Minowada G, Martin G. Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function. Development. 2006;133:33-42 pubmed
    ..These data underscore the importance of controlling the level of FGF gene expression for normal limb development. ..
  72. Bei M, Stowell S, Maas R. Msx2 controls ameloblast terminal differentiation. Dev Dyn. 2004;231:758-65 pubmed
    ..Mice lacking the homeobox gene Msx2 exhibit defects in cusp morphogenesis and in the process of amelogenesis...
  73. Tanaka M, Chen Z, Bartunkova S, Yamasaki N, Izumo S. The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development. 1999;126:1269-80 pubmed
    ..demonstrated that, among 20 candidate genes examined, expression of ANF, BNP, MLC2V, N-myc, MEF2C, HAND1 and Msx2 was disturbed in the mutant heart. Moreover, in the heart of adult chimeric mice generated from Csx/Nkx2...
  74. Davidson D. The function and evolution of Msx genes: pointers and paradoxes. Trends Genet. 1995;11:405-11 pubmed
    ..Here, I review recent evidence that is beginning to address this problem and might eventually increase our understanding of how the vertebrate embryo has evolved. ..