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.