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Development 2016 Nov 01;14321:4016-4026. doi: 10.1242/dev.141812.
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Tril targets Smad7 for degradation to allow hematopoietic specification in Xenopus embryos.

Green YS , Kwon S , Mimoto MS , Xie Y , Christian JL .

In Xenopus laevis, bone morphogenetic proteins (Bmps) induce expression of the transcription factor Gata2 during gastrulation, and Gata2 is required in both ectodermal and mesodermal cells to enable mesoderm to commit to a hematopoietic fate. Here, we identify tril as a Gata2 target gene that is required in both ectoderm and mesoderm for primitive hematopoiesis to occur. Tril is a transmembrane protein that functions as a co-receptor for Toll-like receptors to mediate innate immune responses in the adult brain, but developmental roles for this molecule have not been identified. We show that Tril function is required both upstream and downstream of Bmp receptor-mediated Smad1 phosphorylation for induction of Bmp target genes. Mechanistically, Tril triggers degradation of the Bmp inhibitor Smad7. Tril-dependent downregulation of Smad7 relieves repression of endogenous Bmp signaling during gastrulation and this enables mesodermal progenitors to commit to a blood fate. Thus, Tril is a novel component of a Bmp-Gata2 positive-feedback loop that plays an essential role in hematopoietic specification.

PubMed ID: 27633996
PMC ID: PMC5117148
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: fn1 gata1 gata2 hba3 mapk1 msx1 myc odc1 smad1 smad6.2 smad7 szl tal1 tbxt tril ventx2 ventx2.2
GO keywords: BMP signaling pathway [+]
Antibodies: Acta1 Ab6 Mapk1 Ab10 Mapk1 Ab14 Myc Ab9 Smad1 Ab7 Smad1 Ab8
Morpholinos: gata2 MO1 gata2 MO2 tril MO1 tril MO2

Article Images: [+] show captions
References [+] :
Bai, A nuclear antagonistic mechanism of inhibitory Smads in transforming growth factor-beta signaling. 2002, Pubmed