Specification of germ cell fate in mice

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Abstract
An early fundamental event during development is the segregation of germ cells from somatic cells. In many organisms, this is accomplished by the inheritance of preformed germ plasm, which apparently imposes transcriptional repression to prevent somatic cell fate. However, in mammals, pluripotent epiblast cells acquire germ cell fate in response to signalling molecules. We have used single cell analysis to study how epiblast cells acquire germ cell competence and undergo specification. Germ cell competent cells expressFragilisand initially progress towards a somatic mesodermal fate. However, a subset of these cells, the future primordial germ cells (PGCs), then shows rapid upregulation ofFragiliswith concomitant transcriptional repression of a number of genes, includingHoxandSmadgenes. This repression may be a key event associated with germ cell specification. Furthermore, PGCs expressStellaand other genes, such asOct–4that are associated with pluripotency. While these molecules are also detected in mature oocytes as maternally inherited factors, their early role is to regulate development and maintain pluripotency, and they do not serve the role of classical germline determinants.