Genomes and Genes
Gene Symbol: Smad5
Description: SMAD family member 5
Alias: 1110051M15Rik, AI451355, Dwf-C, Madh5, MusMLP, mothers against decapentaplegic homolog 5, MAD homolog 5, Smad 5, dwarfin-C, mSmad5, mothers against DPP homolog 5
- Zwijsen A, van Grunsven L, Bosman E, Collart C, Nelles L, Umans L, et al. Transforming growth factor beta signalling in vitro and in vivo: activin ligand-receptor interaction, Smad5 in vasculogenesis, and repression of target genes by the deltaEF1/ZEB-related SIP1 in the vertebrate embryo. Mol Cell Endocrinol. 2001;180:13-24 pubmed..We then illustrate how Smad5 knockout mice and an overexpression approach with a truncated TGFbeta type II receptor in the mouse embryo can ..
- Ikeya M, Fukushima K, Kawada M, Onishi S, Furuta Y, Yonemura S, et al. Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors. Dev Biol. 2010;337:405-14 pubmed publisher..These findings revealed the molecular hierarchy between extracellular modifiers that orchestrate local BMP signal peaks in the organogenetic microenvironment. ..
- Korchynskyi O, Ten Dijke P. Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter. J Biol Chem. 2002;277:4883-91 pubmed..Our results provide important new insights into how the BMP/Smad pathway can specifically activate target genes. ..
- Parikh P, Hao Y, Hosseinkhani M, Patil S, Huntley G, Tessier Lavigne M, et al. Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons. Proc Natl Acad Sci U S A. 2011;108:E99-107 pubmed publisher..Together, our results identify a therapeutic target to promote axonal regeneration after SCI. ..
- Tremblay K, Dunn N, Robertson E. Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation. Development. 2001;128:3609-21 pubmed..An examination of the expression domains of Smad1, Smad5 and Smad8 in early mouse embryos show that, while Smad1 is uniquely expressed in the visceral endoderm at 6...
- Murashima Suginami A, Takahashi K, Sakata T, Tsukamoto H, Sugai M, Yanagita M, et al. Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse. Biochem Biophys Res Commun. 2008;369:1012-6 pubmed publisher..Based upon these results, we conclude that enhanced BMP signaling results in supernumerary teeth and BMP signaling was modulated by Wnt signaling in the USAG-1 deficient mouse model. ..
- Binato R, Alvarez Martinez C, Pizzatti L, Robert B, Abdelhay E. SMAD 8 binding to mice Msx1 basal promoter is required for transcriptional activation. Biochem J. 2006;393:141-50 pubmed..Binding of purified SMAD 1 and SMAD 4 as well as supershift assay with SMAD 1/SMAD 5/SMAD 8 antibody proved that a SMAD protein is present in this complex...
- Yang X, Castilla L, Xu X, Li C, Gotay J, Weinstein M, et al. Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development. 1999;126:1571-80 pubmed..growth factor-beta (TGF-beta) signals are mediated by a family of at least nine SMAD proteins, of which SMAD5 is thought to relay signals of the bone morphogenetic protein (BMP) pathway...
- Fei T, Xia K, Li Z, Zhou B, Zhu S, Chen H, et al. Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination. Genome Res. 2010;20:36-44 pubmed publisher..Combined with computational analysis, our results suggest that SMAD-mediated BMP signaling balances self-renewal versus differentiation by modulating a set of developmental regulators. ..
- Middlebrook B, Eldin K, Li X, Shivasankaran S, Pangas S. Smad1-Smad5 ovarian conditional knockout mice develop a disease profile similar to the juvenile form of human granulosa cell tumors. Endocrinology. 2009;150:5208-17 pubmed publisher..The TGFbeta family is active in mouse Smad1-Smad5 double knockout tumors, and here we show that this pathway, but not the beta-catenin pathway, is activated in ..
- Du Y, Xiao Q, Yip H. Regulation of retinal progenitor cell differentiation by bone morphogenetic protein 4 is mediated by the smad/id cascade. Invest Ophthalmol Vis Sci. 2010;51:3764-73 pubmed publisher..CONCLUSIONS. These results suggest that Id genes are one of the potential targets of BMP signaling in the differentiation of RPCs. ..
- Arnold S, Maretto S, Islam A, Bikoff E, Robertson E. Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo. Dev Biol. 2006;296:104-18 pubmedThree closely related mammalian R-Smads, namely Smad1, Smad5 and Smad8, are activated by BMP receptors. Here we have taken a genetic approach to further dissect their possibly unique and/or shared roles during early mouse development...
- Pangas S, Li X, Umans L, Zwijsen A, Huylebroeck D, Gutierrez C, et al. Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Mol Cell Biol. 2008;28:248-57 pubmed..Single conditional knockouts for Smad1 or Smad5 or mice homozygous null for Smad8 are viable and fertile...
- Li L, Lin M, Wang Y, Cserjesi P, Chen Z, Chen Y. BmprIa is required in mesenchymal tissue and has limited redundant function with BmprIb in tooth and palate development. Dev Biol. 2011;349:451-61 pubmed publisher..Our results demonstrate an essential role for BmprIa in the mesenchymal component and a limited functional redundancy between BmprIa and BmprIb in a tissue-specific manner during tooth and palate development...
- Yang T, Mendoza Londono R, Lu H, Tao J, Li K, Keller B, et al. E-selectin ligand-1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-beta. J Clin Invest. 2010;120:2474-85 pubmed publisher..This study identifies what we believe to be a novel intracellular mechanism for regulating TGF-beta during skeletal development and homeostasis. ..
- 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..Lastly, we provide evidence that Prx homeobox genes repress expression of an Msx2 transgene, previously shown to be Bmp4-responsive, revealing a mechanism for differential regulation of Msx1 and Msx2 by Bmp signaling. ..
- Blank U, Brown A, Adams D, Karolak M, Oxburgh L. BMP7 promotes proliferation of nephron progenitor cells via a JNK-dependent mechanism. Development. 2009;136:3557-66 pubmed publisher..Activation of Jun and ATF2 is severely diminished in Bmp7-null kidneys, providing an important in vivo correlate. BMP7 thus promotes proliferation directly in nephron progenitors by activating the JNK signaling circuitry. ..
- Spoelgen R, Hammes A, Anzenberger U, Zechner D, Andersen O, Jerchow B, et al. LRP2/megalin is required for patterning of the ventral telencephalon. Development. 2005;132:405-14 pubmed..Because megalin mediates endocytic uptake and degradation of BMP4, these findings indicate a role for megalin in neural tube specification, possibly by acting as BMP4 clearance receptor in the neuroepithelium. ..
- Yoon B, Ovchinnikov D, Yoshii I, Mishina Y, Behringer R, Lyons K. Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo. Proc Natl Acad Sci U S A. 2005;102:5062-7 pubmed..In summary, our study demonstrates that BMPR1A and BMPR1B are functionally redundant during early chondrogenesis and that BMP signaling is required for chondrocyte proliferation, survival, and differentiation in vivo. ..
- Sowa H, Kaji H, Hendy G, Canaff L, Komori T, Sugimoto T, et al. Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2. J Biol Chem. 2004;279:40267-75 pubmed..In osteoblasts the interaction of menin and the transforming growth factor-beta/Smad3 pathway negatively regulates the BMP-2/Smad1/5- and Runx2-induced transcriptional activities leading to inhibition of late-stage differentiation. ..
- Weinstein M, Yang X, Deng C. Functions of mammalian Smad genes as revealed by targeted gene disruption in mice. Cytokine Growth Factor Rev. 2000;11:49-58 pubmed..These experiments have shown that Smad2 and Smad4 are needed for gastrulation, Smad5 for angiogenesis, and Smad3 for establishment of the mucosal immune response and proper development of the ..
- Chang H, Huylebroeck D, Verschueren K, Guo Q, Matzuk M, Zwijsen A. Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development. 1999;126:1631-42 pubmedb>Smad5 has been implicated as a downstream signal mediator for several bone morphogenetic proteins (BMPs). To understand the in vivo function of Smad5, we generated mice deficient in Smad5 using embryonic stem (ES) cell technology...
- Flanders K, Kim E, Roberts A. Immunohistochemical expression of Smads 1-6 in the 15-day gestation mouse embryo: signaling by BMPs and TGF-betas. Dev Dyn. 2001;220:141-54 pubmed..Differences are observed in the nuclear versus cytoplasmic localization among the Smads in different cell types or tissues, suggesting selective activation of Smads during this stage of development. ..
- Ohta S, Suzuki K, Tachibana K, Tanaka H, Yamada G. Cessation of gastrulation is mediated by suppression of epithelial-mesenchymal transition at the ventral ectodermal ridge. Development. 2007;134:4315-24 pubmed..These indicate that the inhibition of Bmp signaling by temporal and/or spatial Nog expression suppresses EMT and leads to the cessation of the ingressive cell movement from the VER at the end of gastrulation. ..
- Michos O, Gonçalves A, Lopez Rios J, Tiecke E, Naillat F, Beier K, et al. Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis. Development. 2007;134:2397-405 pubmed
- Wong Y, Behringer R, Kwan K. Smad1/Smad5 signaling in limb ectoderm functions redundantly and is required for interdigital programmed cell death. Dev Biol. 2012;363:247-57 pubmed publisher..investigate the role of Smad proteins in BMP-regulated AER functions in limb development, we inactivated Smad1 and Smad5 selectively in AER and ventral ectoderm of developing limb, using Smad1 or/and Smad5 floxed alleles and an En1(Cre/..
- Canali S, Core A, Zumbrennen Bullough K, Merkulova M, Wang C, Schneyer A, et al. Activin B Induces Noncanonical SMAD1/5/8 Signaling via BMP Type I Receptors in Hepatocytes: Evidence for a Role in Hepcidin Induction by Inflammation in Male Mice. Endocrinology. 2016;157:1146-62 pubmed publisher..ACVR2B, noncanonical BMP type I receptors activin receptor-like kinase 2 and activin receptor-like kinase 3, and SMAD5. The coreceptor hemojuvelin binds to activin B and facilitates activin B-SMAD1/5/8 signaling...
- Xu B, Chen C, Chen H, Zheng S, Bringas P, Xu M, et al. Smad1 and its target gene Wif1 coordinate BMP and Wnt signaling activities to regulate fetal lung development. Development. 2011;138:925-35 pubmed publisher..To define the intracellular signaling mechanisms by which Bmp4 regulates lung development, BMP-specific Smad1 or Smad5 was selectively knocked out in fetal mouse lung epithelial cells...
- Orvis G, Jamin S, Kwan K, Mishina Y, Kaartinen V, Huang S, et al. Functional redundancy of TGF-beta family type I receptors and receptor-Smads in mediating anti-Mullerian hormone-induced Mullerian duct regression in the mouse. Biol Reprod. 2008;78:994-1001 pubmed publisher..we have determined that two TGF-beta type I receptors (Acvr1 and Bmpr1a) and all three BMP receptor-Smads (Smad1, Smad5, and Smad8) function redundantly in transducing the anti-Müllerian hormone signal required for Müllerian duct ..
- Tanimoto Y, Veistinen L, Alakurtti K, Takatalo M, Rice D. Prevention of premature fusion of calvarial suture in GLI-Kruppel family member 3 (Gli3)-deficient mice by removing one allele of Runt-related transcription factor 2 (Runx2). J Biol Chem. 2012;287:21429-38 pubmed publisher..We propose that targeting Runx2 might provide an attractive way of preventing craniosynostosis in patients. ..
- Liu B, Sun Y, Jiang F, Zhang S, Wu Y, Lan Y, et al. Disruption of Smad5 gene leads to enhanced proliferation of high-proliferative potential precursors during embryonic hematopoiesis. Blood. 2003;101:124-33 pubmed..b>SMAD5, initially considered to mediate bone morphogenetic proteins (BMPs) signals, can also transduce the inhibitory ..
- Valenta T, Gay M, Steiner S, Draganova K, Zemke M, Hoffmans R, et al. Probing transcription-specific outputs of ?-catenin in vivo. Genes Dev. 2011;25:2631-43 pubmed publisher..Our model animals thus allow dissecting signaling and structural functions of ?-catenin in vivo and provide the first genetic tool to generate cells and tissues that entirely and exclusively lack canonical Wnt pathway activity. ..
- Ting M, Wu N, Roybal P, Sun J, Liu L, Yen Y, et al. EphA4 as an effector of Twist1 in the guidance of osteogenic precursor cells during calvarial bone growth and in craniosynostosis. Development. 2009;136:855-64 pubmed publisher..We suggest that the failure of this process in Twist1 and EphA4 mutants is the cause of craniosynostosis. ..
- 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 pubmedb>Smad5 is an intracellular mediator of bone morphogenetic protein (Bmp) signalling...
- Han L, Xu J, Grigg E, Slack M, Chaturvedi P, Jiang R, et al. Osr1 functions downstream of Hedgehog pathway to regulate foregut development. Dev Biol. 2017;427:72-83 pubmed publisher..We conclude that Osr1 is a novel downstream target of HH pathway, required for lung specification, branching morphogenesis and foregut mesenchymal differentiation. ..
- Närhi K, Järvinen E, Birchmeier W, Taketo M, Mikkola M, Thesleff I. Sustained epithelial beta-catenin activity induces precocious hair development but disrupts hair follicle down-growth and hair shaft formation. Development. 2008;135:1019-28 pubmed publisher..Our data suggest that BMPs are downstream of Wnt/beta-catenin and that their interplay may be a critical component in establishing correct patterning of hair follicles through the reaction-diffusion mechanism. ..
- Mansouri Attia N, Tripurani S, Gokul N, Piard H, Anderson M, Eldin K, et al. TGFÎ² signaling promotes juvenile granulosa cell tumorigenesis by suppressing apoptosis. Mol Endocrinol. 2014;28:1887-98 pubmed publisher..deletion in granulosa cells of the bone morphogenetic protein receptor-signaling transcription factors, Smad1 and Smad5, causes development of metastatic granulosa cell tumors that phenocopy the juvenile form of granulosa cell tumors (..
- Mukhopadhyay P, Webb C, Warner D, Greene R, Pisano M. BMP signaling dynamics in embryonic orofacial tissue. J Cell Physiol. 2008;216:771-9 pubmed publisher..Collectively, these data document the existence of a functional Smad-mediated BMP signaling system in cells of the developing murine orofacial region. ..
- Ishibashi O, Ikegame M, Takizawa F, Yoshizawa T, Moksed M, Iizawa F, et al. Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation. J Cell Physiol. 2010;222:465-73 pubmed publisher..These results, taken together, raise a possibility that PDL cells respond to BMP-2 via a unique signaling pathway dependent on endoglin, which is involved in the osteoblastic differentiation and mineralization of the cells. ..
- Morikawa Y, Komori T, Hisaoka T, Senba E. Detailed expression pattern of Foxp1 and its possible roles in neurons of the spinal cord during embryogenesis. Dev Neurosci. 2009;31:511-22 pubmed publisher..These results suggest that Foxp1 may play some important roles in the determination of neuronal fates of the ventral spinal cord, possibly through the suppression of Lhx3 expression. ..
- Wang B, Harrison W, Overbeek P, Zheng H. Transposon mutagenesis with coat color genotyping identifies an essential role for Skor2 in sonic hedgehog signaling and cerebellum development. Development. 2011;138:4487-97 pubmed publisher..Our study identifies an essential function for Skor2 as a novel transcriptional regulator in Purkinje cells that acts upstream of Shh during cerebellum development. ..
- Wandzioch E, Zaret K. Dynamic signaling network for the specification of embryonic pancreas and liver progenitors. Science. 2009;324:1707-10 pubmed publisher..These findings may enhance progenitor cell specification from stem cells for biomedical purposes and can help explain incomplete programming in stem cell differentiation protocols. ..
- Chiga M, Ohmori T, Ohba T, Katabuchi H, Nishinakamura R. Preformed Wolffian duct regulates MÃ¼llerian duct elongation independently of canonical Wnt signaling or Lhx1 expression. Int J Dev Biol. 2014;58:663-8 pubmed publisher..These results suggest that the Wolffian duct regulates MÃ¼llerian duct elongation by currently unidentified mechanisms that are independent of canonical Wnt signaling or Lhx1 expression. ..
- Li Y, Gordon J, Manley N, Litingtung Y, Chiang C. Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis. Dev Biol. 2008;322:145-55 pubmed publisher..Our finding sheds light on human tracheal malformations by providing a novel mouse model implicating Bmp signaling, non-canonical Erk activation and cellular proliferation. ..
- Smart N, Dubé K, Riley P. Identification of Thymosin ?4 as an effector of Hand1-mediated vascular development. Nat Commun. 2010;1:46 pubmed publisher..Thus, we identify an in vivo downstream target of Hand1 and reveal impaired yolk sac vasculogenesis as a primary cause of early embryonic lethality following loss of this critical bHLH factor. ..
- MacGrogan D, D Amato G, Travisano S, Martínez Poveda B, Luxan G, del Monte Nieto G, et al. Sequential Ligand-Dependent Notch Signaling Activation Regulates Valve Primordium Formation and Morphogenesis. Circ Res. 2016;118:1480-97 pubmed publisher..Our studies identify a mechanism of signaling cross talk during valve morphogenesis involved in the origin of congenital heart defects associated with reduced NOTCH function. ..