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XB-ART-58208
iScience June 25, 2021; 24 (6): 102520.
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Pinhead antagonizes Admp to promote notochord formation.

Itoh K , Ossipova O , Sokol SY .


Abstract
Dorsoventral patterning of a vertebrate embryo critically depends on the activity of Smad1 that mediates signaling by BMP proteins, anti-dorsalizing morphogenetic protein (Admp), and their antagonists. Pinhead (Pnhd), a cystine-knot-containing secreted protein, is expressed in the ventrolateral mesoderm during Xenopus gastrulation; however, its molecular targets and signaling mechanisms have not been fully elucidated. Our mass spectrometry-based screen of the gastrula secretome identified Admp as Pnhd-associated protein. We show that Pnhd binds Admp and inhibits its ventralizing activity by reducing Smad1 phosphorylation and its transcriptional targets. Importantly, Pnhd depletion further increased phospho-Smad1 levels in the presence of Admp. Furthermore, Pnhd synergized with Chordin and a truncated BMP4 receptor in the induction of notochord markers in ectoderm cells, and Pnhd-depleted embryos displayed notochord defects. Our findings suggest that Pnhd binds and inactivates Admp to promote notochord development. We propose that the interaction between Admp and Pnhd refines Smad1 activity gradients during vertebrate gastrulation.

PubMed ID: 34142034
Article link: iScience
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: admp angpt4 bambi bmp4 bmp7.1 cdx4 chd1 dand5 dkk1 emilin3 furin lefty myod1 not notum pnhd sfrp2 shh smad1 sox2 szl ventx1.2 ventx2.1 wnt8a
GO keywords: gastrulation [+]
Antibodies: Ctnnb1 Ab12 HA Ab7 Myc Ab2
Morpholinos: pnhd MO4 pnhd MO5 pnhd MO7

GEO Series: GSE168370: NCBI

Article Images: [+] show captions