IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Cerebrospinal fluid-contacting neurons of the spinal cord are a subset of embryonic Gata2+ neurons
Autor/es:
SARTORETTI, M.; DI BELLA, D.; CARCAGNO, A.; PETRACCA, Y.; GOULDING, M.; GUILLERMO MARCOS LANUZA
Lugar:
Chicago, IL, USA
Reunión:
Congreso; Neuroscience Meeting 2009; 2009
Institución organizadora:
Society for Neuroscience
Resumen:
Abstract: In spite of the considerable progress made in understanding early events in cell fate specification, the mechanisms that lead to the generation of diversity of mature neuronal cell types in the adult remain to be elucidated. In the postnatal spinal cord, there is a population of cells with a unique morphology around the ependyma of the central canal, which are known as cerebrospinal fluid-contacting neurons (CCNs). These cells extent a dendritic-like process through the ependymal cell layer into the central canal, and are selectively marked by the TRP channel PKD2L1. Immunohistochemical analysis showed that CCNs express neuronal β-tubulin, but they are negative or are labeled at very low levels with a NeuN antibody. We found that CCNs express the transcription factors Gata2/3, which are specific markers of spinal V2b embryonic interneurons. CCNs can be efficiently labeled with GFP in the Gata2GFP knockin mice. We have also performed lineage-tracing analysis using the Gata3Cre line crossed with GFP reporter animals. This system allowed the identification of the cluster of CCNs in lamina X, distinct to V2b-derived interneurons that locate lateral in lamina VII. In order to determine whether distinct subsets of Gata2/3 neurons correlate with the time of progenitor cell cycle exit, we performed a series of BrdU pulse-labeling experiments. Interestingly we found that CCNs are born from ventral progenitors between E13 and E14, a period when neurogenesis in the neural tube is almost finished. The late birthdate of CCNs contrasts with the earlier development of the population of Gata2/3-V2b interneurons that settle in lamina VII. The generation of early-born V2b cells requires the activity of the transcription factor Foxn4 in their progenitors acting by a mechanism that involves Delta4/Notch signaling pathway. On the contrary, we found that the differentiation of CCNs appears normal in Foxn4-/- and in Presenilin1 mutant mice, indicating that differential genetic mechanisms control the genesis of distinct subsets of Gata2/3 neurons. These results show that dorsoventrally restricted populations of precursors in the developing neural tube can sequentially generate different neuronal subtypes, contributing to the diversification of neuronal fates.