Regulation of ES Cell Lineage Commitment by Mitogen Activated Protein Kinases

¹ INSERM, U626, Marseille, France; Université de Marseille II, Faculté de Médecine, Marseille, France
² Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado
³ INSERM, U568, Nice, France; Université de Nice Sophia-Antipolis, Faculté de Médecine, av de Valombrose, Nice, France

^* To whom correspondence should be addressed. E-mail: Bernard.Binetruy{at}medecine.univ-mrs.fr.

	Abstract

Embryonic Stem (ES) cells can give rise, in vivo, to the ectodermal, endodermal and mesodermal germ layers and, in vitro, can differentiate into multiple cell lineages, offering broad perspectives in regenerative medicine. Understanding the molecular mechanisms governing ES cell commitment is an essential challenge in this field. The Mitogen Activated Protein Kinase (MAPK) pathways, ERK, JNK and p38MAPK, are able to regulate ES commitment from early steps of the process to mature differentiated cells. Whereas the ERK pathway inhibits the self-renewal of ES cells, upon commitment this pathway is involved in the development of extraembryonic tissues, in early mesoderm differentiation and in the formation of mature adipocytes; p38MAPK displays a large spectrum of action from neurons to adipocytes and JNK is involved in both ectoderm and primitive endoderm differentiations. Furthermore, for a given pathway, several of these effects are isoform-dependent, revealing the complexity of the cellular response to activation of MAPK pathways. Regarding tissue regeneration, the potential outcome of systematic analysis of the function of different MAPKs in different ES cell differentiation programs is discussed.