title: Depletion of Suds3 reveals an essential role in early lineage specification.
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.
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, 455, 661 N. Pleasant Street, Amherst, MA 01003, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Xiangpeng
authors.initials: X
authors.lastname: Dai
authors.forename: Mary C
authors.initials: MC
authors.lastname: Wallingford
authors.forename: Jesse
authors.initials: J
authors.lastname: Mager
mesh_terms: D000818:Animals; D053624:Blastocyst Inner Cell Mass / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D004475:Ectoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051519:Fibroblast Growth Factor 4 / Q000378:metabolism / Q000494:pharmacology; D050993:GATA6 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein; D012097:Repressor Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D024002:HMGB Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D055760:SOXF Transcription Factors; C497354:Sds3 protein, mouse; C511606:Sox17 protein, mouse; C527783:Sox2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1