TY - JOUR
T1 - GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst
AU - Schrode, Nadine
AU - Saiz, Néstor
AU - Di Talia, Stefano
AU - Hadjantonakis, Anna Katerina
N1 - Funding Information:
We thank S. Duncan and P. Soriano for Gata6 cKO and Pdgfra H2B-GFP mouse lines, respectively; V. Seshan of the Memorial Sloan Kettering Cancer Center Biostatistics Core Facility for advice on fluorescence intensity data transformations; and M. Kang, J. Nichols, S. Nowotschin, B. Plusa, C. Schroeter, and P. Xenopoulos for discussions and comments on the manuscript. Our work is supported by NIH-R01-HD052115, NIH-R01-DK084391, and NYSTEM (to A.-K.H.) and NIH-K99-HD074670 (to S.D.T.).
PY - 2014/5/27
Y1 - 2014/5/27
N2 - Cells of the inner cell mass (ICM) of the mouse blastocyst differentiate into the pluripotent epiblast or the primitive endoderm (PrE), marked by the transcription factors NANOG and GATA6, respectively. To investigate the mechanistic regulation of this process, we applied an unbiased, quantitative, single-cell-resolution image analysis pipeline to analyze embryos lacking or exhibiting reduced levels of GATA6. We find that Gata6 mutants exhibit a complete absence of PrE and demonstrate that GATA6 levels regulate the timing and speed of lineage commitment within the ICM. Furthermore, we show that GATA6 is necessary for PrE specification by FGF signaling and propose a model where interactions between NANOG, GATA6, and the FGF/ERK pathway determine ICM cell fate. This study provides a framework for quantitative analyses of mammalian embryos and establishes GATA6 as a nodal point in the gene regulatory network driving ICM lineage specification.
AB - Cells of the inner cell mass (ICM) of the mouse blastocyst differentiate into the pluripotent epiblast or the primitive endoderm (PrE), marked by the transcription factors NANOG and GATA6, respectively. To investigate the mechanistic regulation of this process, we applied an unbiased, quantitative, single-cell-resolution image analysis pipeline to analyze embryos lacking or exhibiting reduced levels of GATA6. We find that Gata6 mutants exhibit a complete absence of PrE and demonstrate that GATA6 levels regulate the timing and speed of lineage commitment within the ICM. Furthermore, we show that GATA6 is necessary for PrE specification by FGF signaling and propose a model where interactions between NANOG, GATA6, and the FGF/ERK pathway determine ICM cell fate. This study provides a framework for quantitative analyses of mammalian embryos and establishes GATA6 as a nodal point in the gene regulatory network driving ICM lineage specification.
UR - https://www.scopus.com/pages/publications/84901627728
U2 - 10.1016/j.devcel.2014.04.011
DO - 10.1016/j.devcel.2014.04.011
M3 - Article
C2 - 24835466
AN - SCOPUS:84901627728
SN - 1534-5807
VL - 29
SP - 454
EP - 467
JO - Developmental Cell
JF - Developmental Cell
IS - 4
ER -