Progenitor cell maturation in the developing vertebrate retina.

Progenitor cells in the developing retina initially divide so that each division produces two cells that divide again. Subsequently, progenitor cells change their mode of division so that one or both cells produced by a division can withdraw from the mitotic cycle and differentiate. We asked how these two progenitor cell stages differ molecularly and what controls the switch in the mode of division. We show that early preneurogenic progenitor cells express the transcription factor, Sox2, and the Notch ligand, Delta1. More mature neurogenic progenitor cells express Sox2 and the bHLH transcription factor, E2A, and not Delta1. Notch signaling maintains progenitor cells in the preneurogenic state. Sonic hedgehog expressed by newly differentiating cells initiates maturation of progenitor cells from preneurogenic to neurogenic at the neurogenic front, possibly by down-regulating Delta1 expression. Our results show that the preneurogenic-to-neurogenic transition is a highly organized unidirectional step made in unison by neighboring cells.

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