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The formation of proximal and distal definitive endoderm populations in culture requires p38 MAPK activity


Yap, C and Goh, HN and Familari, M and Rathjen, PD and Rathjen, J, The formation of proximal and distal definitive endoderm populations in culture requires p38 MAPK activity, Journal of Cell Science, 127, (10) pp. 2204-2216. ISSN 0021-9533 (2014) [Refereed Article]

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Copyright Statement

Copyright 2014 Company of Biologists

DOI: doi:10.1242/jcs.134502


Endoderm formation in the mammal is a complex process with two lineages forming during the first weeks of development, the primitive (or extraembryonic) endoderm, which is specified in the blastocyst, and the definitive endoderm that forms later, at gastrulation, as one of the germ layers of the embryo proper. Fate mapping evidence suggests that the definitive endoderm arises as two waves, which potentially reflect two distinct cell populations. Early primitive ectoderm-like (EPL) cell differentiation has been used successfully to identify and characterise mechanisms regulating molecular gastrulation and lineage choice during differentiation. The roles of the p38 MAPK family in the formation of definitive endoderm were investigated using EPL cells and chemical inhibitors of p38 MAPK activity. These approaches define a role for p38 MAPK activity in the formation of the primitive streak and a second role in the formation of the definitive endoderm. Characterisation of the definitive endoderm populations formed from EPL cells demonstrates the formation of two distinct populations, defined by gene expression and ontogeny, that were analogous to the proximal and distal definitive endoderm populations of the embryo. Formation of the proximal definitive endoderm was found to require p38 MAPK activity and is correlated with molecular gastrulation, defined by the expression of brachyury (T). Distal definitive endoderm formation also requires p38 MAPK activity but can form when T expression is inhibited. Understanding lineage complexity will be a prerequisite for the generation of endoderm derivatives for commercial and clinical use.

Item Details

Item Type:Refereed Article
Keywords:Embryonic stem cells, Endoderm, p38 MAP kinase, Gastrulation, BMP4
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell development, proliferation and death
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Rathjen, PD (Professor Peter Rathjen)
UTAS Author:Rathjen, J (Dr Joy Rathjen)
ID Code:92091
Year Published:2014
Web of Science® Times Cited:8
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-06-05
Last Modified:2017-11-07

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