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Dev Biol. 2013 Jan 15;373(2):359-72. doi: 10.1016/j.ydbio.2012.10.026. Epub 2012 Nov 1.

Depletion of Suds3 reveals an essential role in early lineage specification.

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1
Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, 455, 661 N. Pleasant Street, Amherst, MA 01003, USA.

Abstract

Preimplantation development culminates with the emergence of three distinct populations: the inner cell mass, primitive endoderm and trophectoderm. Here, we define the mechanisms underlying the requirement of Suds3 in pre/peri-implantation development. Suds3 knockdown blastocysts exhibit a failure of both trophectoderm proliferation as well as a conspicuous lack of primitive endoderm. Expression of essential lineage factors Nanog, Sox2, Cdx2, Eomes, Elf5 and Sox17 are severely reduced in the absence of Suds3. Importantly, we document deficient FGF4/ERK signaling and show that exogenous FGF4 rescues primitive endoderm formation and trophectoderm proliferation in Suds3 knockdown blastocysts. We also show that Hdac1 knockdown reduces Sox2/FGF4/ERK signaling in blastocysts. Collectively, these data define a role for Suds3 in activation of FGF4/ERK signaling and determine an essential molecular role of Suds3/Sin3/HDAC complexes in lineage specification in vivo.

PMID:
23123966
DOI:
10.1016/j.ydbio.2012.10.026
[Indexed for MEDLINE]
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