Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer Journal Article

Authors: De Miguel, M. P.; Cheng, L.; Holland, E. C.; Federspiel, M. J.; Donovan, P. J.
Article Title: Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer
Abstract: Establishment of the mammalian germ line is a prerequisite for fertility of the adult animal but we know surprisingly little about the molecular mechanisms regulating germ-line development in mammals. Signaling from the c-Kit receptor tyrosine kinase is essential for primordial germ cell (PGC) growth both in vivo and in vitro. Many downstream effectors of the c-Kit signaling pathway have been identified in other cell types but how these molecules control PGC survival and proliferation are unknown. Determination of the c-Kit effectors acting in PGCs has been hampered by the lack of effective methods to easily manipulate gene expression in these cells. We overcame this problem by testing the efficacy of retroviral-mediated gene transfer for manipulating gene expression in mammalian germ cells. We found that PGCs can be successfully infected with a variety of types of retroviruses. We used this method to demonstrate an important role for the AKT kinase in regulating PGC growth. Such technology for manipulating gene expression in PGCs will allow many of the molecular mechanisms regulating germ cell growth, behavior, and differentiation to be comprehensively analyzed.
Keywords: signal transduction; mitogen activated protein kinase; protein kinase b; proto-oncogene proteins; nonhuman; genetic analysis; animal cell; mouse; mammalia; animals; mice; bone marrow cells; stem cell factor; proto-oncogene proteins c-kit; gene expression; embryo; cell line; protein tyrosine kinase; mice, inbred c57bl; gene transfer; transgenic mouse; animalia; avian leukosis virus; mus musculus; genetic vectors; germ cells; germ line; cell culture; protein-serine-threonine kinases; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; cell isolation; retrovirus vector; fibroblasts; cell line, transformed; mitogen-activated protein kinases; src-family kinases; mitogen-activated protein kinase kinases; sirolimus; gene transfer techniques; 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene; 2 (2 amino 3 methoxyphenyl)chromone; ribosomal protein s6 kinases; leukemia virus, murine; unidentified retrovirus; humans; priority journal; article; primordial germ cell
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 99
Issue: 16
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2002-08-06
Start Page: 10458
End Page: 10463
Language: English
DOI: 10.1073/pnas.122249399
PUBMED: 12140361
PROVIDER: scopus
PMCID: PMC124938
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. Eric Holland
    220 Holland