Diversification of neuronal cell fates in the developing spinal cord: timing of differentiation and positionally restricted progenitor.

GUILLERMO MARCOS LANUZA

Santa Cruz, Chile

Congreso; International Meeting Latin American Society Developmental Biology; 2010

Latin American Society Developmental Biology

During embryonic development, motoneurons and different classes of spinal cord interneurons arise from defined pools of progenitor cells located at specific positions along the dorso-ventral axis of the neural tube. Recent studies in the mouse and fish have provided compelling evidence that distinct populations of ventral spinal interneurons (V0-V3) play dedicated roles in the neuronal networks that control motor reflexes and locomotion. Despite the considerable progress made in understanding cell fate specification, many aspects of how presumably homogenous groups diversify to generate the highly specialized neuronal cell types in the adult remain to be established. We have recently identified a novel subset of immature neurons in the proximity of the central canal of the spinal cord, termed CCNs, which express the transcription factors Gata2 and Gata3, classical markers of V2 neuronal identity. Genetic fate mapping in the mouse and positional analysis with respect to dorso-ventral patterning genes (Nkx6.1, Pax6, Nkx2.2, Ascl1) indicate that CCNs are a bonafide subset of V2 neurons, descendents from p2 ventral progenitors. However, contrary to the early birth of V2a/V2b motor-related interneurons, CCNs are generated late during mouse embryonic development, at stages previously assumed to be exclusively gliogenic. Moreover, we have found that distinct genetic mechanisms control early and late V2 neuronal specification. While the transcription factor Foxn4 governs early V2 identity, it is dispensable for CCN differentiation. In contrast, the bHLH proneural transcription factor Ascl1, by acting in a cell autonomous manner, differentially governs the development of CCNs. In summary, our results demonstrate that p2 ventral neural tube progenitors give rise to V2a and V2b interneurons, as well as CCNs and astrocytes, demonstrating a hitherto unforeseen degree of diversification. In addition, these experiments suggest that dorsoventrally restricted domains of progenitors can sequentially differentiate into separate neuronal subtypes, therefore contributing to the increase of neuronal cell fates in the developing central nervous system.