Depletion of Suds3 reveals an essential role in early lineage specification

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 o...

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Bibliographic Details
Published in:Developmental biology 2013-01, Vol.373 (2), p.359-372
Main Authors: Zhang, Kun, Dai, Xiangpeng, Wallingford, Mary C., Mager, Jesse
Format: Article
Language:English
Subjects:
Animals
blastocyst
Blastocyst Inner Cell Mass - cytology
Blastocyst Inner Cell Mass - drug effects
Blastocyst Inner Cell Mass - metabolism
Body Patterning - drug effects
Body Patterning - genetics
cell communication
cell differentiation
Cell Lineage - drug effects
Cell Lineage - genetics
cell proliferation
Ectoderm - cytology
Ectoderm - drug effects
Ectoderm - metabolism
embryo implantation
Extracellular Signal-Regulated MAP Kinases - metabolism
Female
Fibroblast Growth Factor 4 - metabolism
Fibroblast Growth Factor 4 - pharmacology
GATA6 Transcription Factor - metabolism
Gene Expression Profiling
Gene Expression Regulation, Developmental - drug effects
Gene Knockdown Techniques
Hdac1
Histone Deacetylase 1 - metabolism
HMGB Proteins - genetics
HMGB Proteins - metabolism
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
ICM
in vivo studies
Lineage specification
Mice
Nanog Homeobox Protein
population
Primitive endoderm
Repressor Proteins - deficiency
Repressor Proteins - genetics
Repressor Proteins - metabolism
Signal Transduction - drug effects
Sin3a
SOXB1 Transcription Factors - genetics
SOXB1 Transcription Factors - metabolism
SOXF Transcription Factors - genetics
SOXF Transcription Factors - metabolism
Suds3
Trophectoderm
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Summary: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. ► Suds3 is required in vivo for specification of trophoblast and primitive endoderm. ► Suds3 is required proper ICM/Epiblast gene expression and Sox2-FGF4-ERK signaling. ► Sox2 localizes to future ICM cell nuclei prior to Oct4 restriction.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2012.10.026