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Published September 1995 | public
Journal Article

Postmigratory Neural Crest Cells Expressing c-RET Display Restricted Developmental and Proliferative Capacities


c-RET is an orphan receptor tyrosine kinase essential for enteric neurogenesis in mice and is involved in several human genetic disorders. RET is also one of the earliest surface markers expressed by postmigratory neural crest cells in the gut. We generated anti-RET monoclonal antibodies to isolate such cells. We find that RET+ cells are antigenically and functionally distinct from neural crest stem cells (NCSCs) characterized previously. Unlike NCSCs, which are RET− and MASH1−, most RET+ cells express MASH1. Moreover, unlike NCSCs, which are multipotent and have high proliferative capacity, many RET+ cells generate only neurons following a limited number of divisions. This behavior is observed even in the presence of glial growth factor, a polypeptide that suppresses neuronal and promotes glial differentiation by NCSCs. These data provide direct evidence for the existence of committed neuronal progenitor cells and support a model of neural crest lineage diversification by progressive restriction of developmental potential.

Additional Information

© 1995 by Cell Press. Under an Elsevier user license. Received 23 May 1995, Revised 22 June 1995, Available online 1 June 2004. We thank Vassilis Pachnis for providing a mouse c-RET cDNA clone; Larry Gerace for suggesting the use of Armenian hamsters; Pamela Bjorkman for suggesting the use of the pGS amplification system and expressing RET as a PI-iinked fusion; Ashly Lawton (Celltech Biologics, Inc.) for making the pGS system available; Ron Barrett (Affymax, Inc.) for providing the HPAP PI-attachment sequence; monoclonal antibody 179, and valuable advice; Susan Ou for help in antibody production; Janet Baer, D.V.M., for assistance with animal procedures; Nirao Shah for providing NCSCs for control experiments and for valuable advice and discussions; Rochelle Diamond for developing cell-sorting procedures; Marc Marchionni for providing rhGGFII; Steve Padilla and Ling Wang for plasmid preps and tissue culture assistance, respectively; and Kai Zinn, Nirao Shah, Chris Schoenherr, and Scott Fraser for critical comments on the manuscript. D. J. A. is an Associate Investigator of the Howard Hughes Medical Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC Section 1734 solely to indicate this fact.

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August 20, 2023
October 20, 2023