期刊
DEVELOPMENTAL BIOLOGY
卷 219, 期 2, 页码 299-314出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/dbio.2000.9622
关键词
CDK inhibitor; neurogenesis; proliferation; gene gun; particle-mediated gene transfer; neuron; glia
资金
- NEI NIH HHS [F32 EY006656-03, F32 EY006656, EY66056] Funding Source: Medline
- NINDS NIH HHS [R01 NS28308] Funding Source: Medline
The cyclin-dependent kinase inhibitor protein, p27(Kip1), is necessary for the timing of cell cycle withdrawal that precedes terminal differentiation in oligodendrocytes of the optic nerve. Although p27(Kip1) is widely expressed in the developing central nervous system, it is not known whether this protein has a similar role in neuronal differentiation. To address this issue, we have examined the expression and function of p27(Kip1) in the developing retina, a well-characterized part of the central nervous system. p27(Kip1) is expressed in a pattern coincident with the onset of differentiation of most retinal cell types. In vitro analyses show that p27(Kip1) accumulation in retinal cells correlates with cell cycle withdrawal and differentiation, and when overexpressed, p27(Kip1) inhibits proliferation of the progenitor cells. Furthermore, the histogenesis of photoreceptors and Muller glia is extended in the retina of p27(Kip1)-deficient mice. Finally, we examined the adult retinal dysplasia in p27(Kip1)-deficient mice with cell-type-specific markers. Contrary to previous suggestions that the dysplasia is caused by excess production of photoreceptors, we suggest that the dysplasia is due to the displacement of reactive Muller glia into the layer of photoreceptor outer segments. These results demonstrate that p27(Kip1) is part of the molecular mechanism that controls the decision of multipotent central nervous system progenitors to withdraw from the cell cycle. Second, postmitotic Muller glia have a novel and intrinsic requirement for p27(Kip1) in maintaining their differentiated state. (C) 2000 Academic Press.
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