High impact information on smad5

• The phenotype of laf mutants and alk8 morphants can be rescued by injected mRNA encoding Alk8 or the Bmp-regulated transcription factor Smad5, but not by mRNA encoding Bmp2b or Bmp7 [1].
• Double mutant analyses and RNA injection experiments show that sbn and bmp2b interact and that sbn acts downstream of Bmp2b signaling to mediate Bmp2b autoregulation during early dorsoventral (D-V) pattern formation [2].
• However, in somitabun(-) (sbn(-)) embryos, which probably retain higher residual Bmp activity, it is the sensory neurons and not the interneurons that are expanded [3].
• The weakest phenotype is a reduction in the ventral tail fin, observed as a dominant phenotype of swirl, piggytail, and somitabun and a recessive phenotype of mini fin, lost-a-fin and some piggytail alleles [4].
• Mutations in the piggytail gene display an unusual dominance that depends on both a maternal and zygotic heterozygous genotype, while somitabun is a fully penetrant dominant maternal-effect mutation [4].

Biological context of smad5

• Taking advantage of the maternal effect of a zebrafish smad5 null mutation (Mm169), we investigate the effect of early signaling by members of the bone morphogenetic proteins (Bmps) on eye field patterning and optic vesicle morphogenesis [5].
• However, it requires Bmp signal transduction through Alk8 and Smad5 to negatively regulate Ca(2+)/Cadherin-dependent cell-cell adhesiveness [6].

Anatomical context of smad5

• We observe a loss in neural crest progenitors in swirl/bmp2b mutant embryos, while somitabun mutants display an opposite, dramatic expansion of the prospective neural crest [7].
• Examination of dorsally and ventrally restricted markers during gastrulation reveals a successive reduction and reciprocal expansion in nonneural and neural ectoderm, respectively, in snailhouse, somitabun, and swirl mutant embryos, with swirl/bmp2b mutants exhibiting almost no nonneural ectoderm [7].
• In the strong phenotypes, displayed hy homozygous embryos of snailhouse, swirl and somitabun, the somites circle around the embryo and the midbrain region is expanded laterally [4].
• Early expression of foxc1a in the paraxial mesoderm is modified in chordino, swirl, somitabun, and spadetail mutants [8].

Other interactions of smad5

• Injection studies and mutant analyses suggest that the ventral smad1 expression is positively regulated by Bmp2b, but not by Bmp4 signaling, whereas smad5 expression is independent of Bmp2b [9].
• They do not respond to injected bmp2b mRNA, indicating that Smad5 is absolutely essential for ventral development and Bmp2/7 signaling [10].
• Embryos lacking maternal Smad5 function (Mm169(-/-) embryos) are even more strongly dorsalized thanbmp2b or bmp7 null mutants [10].
• We have previously shown that the maternal effect dorsalization of zebrafish embryos from sbn(dtc24) heterozygous mothers is caused by a dominant negative mutation in Smad5, a transducer of ventralizing signaling by the bone morphogenetic proteins Bmp2b and Bmp7 [10].
• Morpholino phenocopies of the swirl, snailhouse, somitabun, minifin, silberblick, and pipetail mutations [11].

References