High impact information on Smad9

• Although Smad8(Deltaexon3/Deltaexon3) embryos are phenotypically normal, homozygotes of another hypomorphic allele of Smad8 (Smad8(3loxP)) containing a neomycin cassette within intron 3, phenocopy an embryonic brain defect observed in roughly 22% of Smad1(+/)(-) embryos analyzed at embryonic day 11 [1].
• Müllerian duct regression can also be inhibited or accelerated by siRNA targeting Smad8 and Smad5, respectively [2].
• However, Smad8 was constitutively phosphorylated, and no further phosphorylation or nuclear accumulation of Smad8 by BMP-6 was observed [3].
• Three closely related mammalian R-Smads, namely Smad1, Smad5 and Smad8, are activated by BMP receptors [4].
• Smad8 is initially expressed only in the visceral yolk sac (VYS) endoderm and shows a highly restricted pattern of expression in the embryo proper at later stages [4].

Biological context of Smad9

• Smad8 and Smad4 cooperatively induced the promoter of Xvent2, a homeobox gene that responds specifically to BMP signaling [5].
• (3) TIS21 regulates embryo development by activating BMP signal through interaction with Smad 1 and Smad 8, thereby regulating vertebral patterning in mice [6].

Anatomical context of Smad9

• The presence of Smad8 mRNA in mouse calvaria cells and osteoblasts suggests a role of Smad8 in the osteoblast differentiation and maturation [5].
• Smad1 and Smad8 function similarly in mammalian central nervous system development [1].

Associations of Smad9 with chemical compounds

• BMP exert their biologic effects via binding to two types of serine/threonine kinase BMP receptors, activation of which leads to phosphorylation and translocation into the nucleus of intracellular signaling molecules, including Smad1, Smad5, and Smad8 ("canonical" BMP signaling pathway) [7].

References