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Gene Review

smad1  -  SMAD family member 1

Danio rerio

Synonyms: MAD homolog 1, Mothers against DPP homolog 1, Mothers against decapentaplegic homolog 1, SMAD 1, SO:0000704, ...
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High impact information on smad1

  • Complete loss of Nodal signaling results in a more severe phenotype than loss of both Bon and Sur, indicating that additional Smad-associated transcription factors remain to be identified that act as components of the Nodal signaling pathway [1].
  • Antibodies specific for the phosphorylated, activated form of Smad1/5, show that BMP signaling is nearly absent in gastrula lacking both maternal and zygotic Laf/Alk8 activity, providing further evidence that Laf/Alk8 transduces a BMP signal [2].
  • Induction of anterior neuroectoderm, giving rise to fore- and midbrain, is accomplished by Bmp inhibition, with Fgfs playing a moderate posteriorizing/patterning role, possibly by blocking Bmp signaling at the level of Smad proteins [3].
  • smad genes encode transcription factors involved in the signal transduction of members of the TGFbeta superfamily [4].
  • In contrast to the C-terminal MH2 domain of Smad2, the C-terminal region of Smad1 and Smad5 lead to pleiotropic effects in embryos giving rize to both dorsalized and ventralized characteristics in injected embryos [5].

Biological context of smad1


Anatomical context of smad1

  • During later stages of development, smad1 is expressed in eyes, dorsal cells of rhombomeres 1, 3, and 5, and somites, with highest mRNA levels in the presumptive sclerotome and adaxial regions near the notochord [7].

Other interactions of smad1

  • In contrast to Smad1, neither Smad2 nor Smad5 caused a detectable effect when expressed as full-length molecules suggesting that these latter two Smads are more dependent on activation by the cognate TGFbeta ligands [5].
  • Also, the dorsalized phenotype of bmp2b-mutant embryos can be rescued by exogenous Smad1, but not by Smad5 [7].

Analytical, diagnostic and therapeutic context of smad1

  • The pattern of expression becomes progressively restricted during somitogenesis suggesting that at later stages not only the distribution of the TGFbeta signal but also that of the intracellular smad signal transducer determine the regionally restricted effects of TGFbeta signalling [5].


  1. Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction. Kunwar, P.S., Zimmerman, S., Bennett, J.T., Chen, Y., Whitman, M., Schier, A.F. Development (2003) [Pubmed]
  2. Lost-a-fin encodes a type I BMP receptor, Alk8, acting maternally and zygotically in dorsoventral pattern formation. Mintzer, K.A., Lee, M.A., Runke, G., Trout, J., Whitman, M., Mullins, M.C. Development (2001) [Pubmed]
  3. Fgf signaling induces posterior neuroectoderm independently of Bmp signaling inhibition. Rentzsch, F., Bakkers, J., Kramer, C., Hammerschmidt, M. Dev. Dyn. (2004) [Pubmed]
  4. Cloning and characterization of zebrafish smad2, smad3 and smad4. Dick, A., Mayr, T., Bauer, H., Meier, A., Hammerschmidt, M. Gene (2000) [Pubmed]
  5. Characterization of zebrafish smad1, smad2 and smad5: the amino-terminus of smad1 and smad5 is required for specific function in the embryo. Müller, F., Blader, P., Rastegar, S., Fischer, N., Knöchel, W., Strähle, U. Mech. Dev. (1999) [Pubmed]
  6. Promoter activity of the zebrafish bhikhari retroelement requires an intact activin signaling pathway. Vogel, A.M., Gerster, T. Mech. Dev. (1999) [Pubmed]
  7. Smad1 and Smad5 have distinct roles during dorsoventral patterning of the zebrafish embryo. Dick, A., Meier, A., Hammerschmidt, M. Dev. Dyn. (1999) [Pubmed]
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