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Amnion signals are essential for mesoderm formation in primates
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Amnion signals are essential for mesoderm formation in primates
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Journal Article
Amnion signals are essential for mesoderm formation in primates
2021
Overview
Embryonic development is largely conserved among mammals. However, certain genes show divergent functions. By generating a transcriptional atlas containing >30,000 cells from post-implantation non-human primate embryos, we uncover that
ISL1
, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amnion. CRISPR/Cas9-targeting of
ISL1
results in non-human primate embryos which do not yield viable offspring, demonstrating that
ISL1
is critically required in primate embryogenesis. On a cellular level, mutant
ISL1
embryos display a failure in mesoderm formation due to reduced BMP4 signaling from the amnion. Via loss of function and rescue studies in human embryonic stem cells we confirm a similar role of
ISL1
in human in vitro derived amnion. This study highlights the importance of the amnion as a signaling center during primate mesoderm formation and demonstrates the potential of in vitro primate model systems to dissect the genetics of early human embryonic development.
Human and murine embryonic development has disparities, highlighting the need for primate systems. Here, the authors construct a post-implantation transcriptional atlas from non-human primate embryos and show ISL1 controls a gene regulatory network in the amnion required for mesoderm formation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/1
/ 38/39
/ 45/41
/ Amnion
/ Animals
/ Bone Morphogenetic Protein 4 - metabolism
/ CRISPR
/ Embryos
/ Female
/ Gene Expression Regulation, Developmental
/ Genetics
/ Humanities and Social Sciences
/ LIM-Homeodomain Proteins - genetics
/ LIM-Homeodomain Proteins - metabolism
/ Macaca fascicularis - embryology
/ Macaca fascicularis - genetics
/ Macaca fascicularis - metabolism
/ Mesoderm
/ Primates
/ Science
