19658195

pubmed:Citation

2

Recent studies have shown that the nuclear factor I (NFI) family controls multiple stages of the postmitotic differentiation of cerebellar granule neurons (CGNs). Regulation of cell-cell signaling is an integral part of this NFI program, which involves expression of the cell adhesion molecules N cadherin and ephrin B1 throughout postmitotic CGN development. Here, we identify two additional downstream targets of NFI that are involved in extracellular CGN interactions. The cell adhesion molecule Tag-1 is highly enriched in CGNs undergoing parallel fiber formation and is down-regulated prior to onset of radial migration. We found that Tag-1 expression was strongly reduced by NFI dominant repression in immature primary CGNs and in the cerebella of E18 Nfib-null mice. Transient transfection and chromatin immunoprecipitation suggested that the Tag-1 gene is directly regulated by NFI. Furthermore, functional, Nfi knockout and chromatin immunoprecipitation studies implicated Wnt7a as a direct target of NFI in maturing CGNs. Wnt7a is secreted by developing CGNs and is required for maturation of mossy fiber-CGN synaptic rosettes. Consistent with this, synapsin I was greatly reduced within the internal granule cell layer of P17 Nfia-null mice. These findings indicated that NFI controls CGN postmitotic maturation through a combination of extracellular signaling molecules that operate either continuously to regulate multiple stages of development (N cadherin and ephrin B1) or primarily at early (Tag-1) or late (Wnt7a) maturation steps. They also illustrate the importance of NFI as a critical link between cell-intrinsic mechanisms and cell-cell interactions in the development of the mouse cerebellum.

eng

IM

MEDLINE

1097-4547

2009 Wiley-Liss, Inc.

1

NLM

258-65

pubmed-meshheading:19658195-Animals, pubmed-meshheading:19658195-Cadherins, pubmed-meshheading:19658195-Cell Adhesion Molecules, Neuronal, pubmed-meshheading:19658195-Cell Communication, pubmed-meshheading:19658195-Cells, Cultured, pubmed-meshheading:19658195-Cerebellum, pubmed-meshheading:19658195-Chromatin, pubmed-meshheading:19658195-Contactin 2, pubmed-meshheading:19658195-Ephrin-B1, pubmed-meshheading:19658195-Mice, pubmed-meshheading:19658195-Mice, Inbred C57BL, pubmed-meshheading:19658195-Mice, Knockout, pubmed-meshheading:19658195-Mitosis, pubmed-meshheading:19658195-NFI Transcription Factors, pubmed-meshheading:19658195-Neurons, pubmed-meshheading:19658195-Regulon, pubmed-meshheading:19658195-Signal Transduction, pubmed-meshheading:19658195-Time Factors, pubmed-meshheading:19658195-Wnt Proteins

Targets of the nuclear factor I regulon involved in early and late development of postmitotic cerebellar granule neurons.

Journal Article, Research Support, N.I.H., Extramural