期刊
DEVELOPMENTAL BIOLOGY
卷 349, 期 2, 页码 270-282出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2010.11.008
关键词
Fibroblast growth factor; Isthmic organizer; Neuronal stem cell; Hes1; Neurogenesis; Basal lamina
资金
- Academy of Finland
- Biocentrum Helsinki
- Sigrid Juselius Foundation
- Finnish Cultural Foundation
- Helsinki Graduate School in Biotechnology and Molecular Biology
For the correct development of the central nervous system, the balance between self-renewing and differentiating divisions of the neuronal progenitors must be tightly regulated. To maintain their self-renewing identity, the progenitors need to retain both apical and basal interfaces. However, the identities of fate-determining signals which cells receive via these connections, and the exact mechanism of their action, are poorly understood. The conditional inactivation of Fibroblast growth factor (FGF) receptors 1 and 2 in the embryonic mouse midbrain-hindbrain area results in premature neuronal differentiation. Here, we aim to elucidate the connection between FGF signaling and neuronal progenitor maintenance. Our results reveal that the loss of FGF signaling leads to downregulation of Hes1 and upregulation of Ngn2, Dll1, and p57 in the ventricular zone (VZ) cells, and that this increased neurogenesis occurs cell-autonomously. Yet the cell cycle progression, apico-basal-polarity, cell-cell connections, and the positioning of mitotic spindle in the mutant VZ appear unaltered. Interestingly. FGF8-protein is highly concentrated in the basal lamina. Thus, FGFs may act through basal processes of neuronal progenitors to maintain their progenitor status. Indeed, midbrain neuronal progenitors deprived in vitro of FGFs switched from symmetrical proliferative towards symmetrical neurogenic divisions. We suggest that FGF signaling in the midbrain VZ is cell-autonomously required for the maintenance of symmetrical proliferative divisions via Hes1-mediated repression of neurogenic genes. (C) 2010 Elsevier Inc. All rights reserved.
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