Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina

被引:83
作者
Miyawaki, T
Uemura, A
Dezawa, M
Yu, RT
Ide, C
Nishikawa, S
Honda, Y
Tanabe, Y
Tanabe, T
机构
[1] Kyoto Univ, Grad Sch Med, Dept Ophthalmol, Sakyo Ku, Kyoto 6068507, Japan
[2] RIKEN Ctr Dev Biol, Kobe, Hyogo 6500047, Japan
[3] Kyoto Univ, Grad Sch Med, Dept Anat & Neurobiol, Kyoto 6068501, Japan
[4] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
[5] Mitsubishi Kagaku Inst Life Sci, Neurol Org Res Team, Tokyo 1948511, Japan
关键词
Tlx; astrocyte; retinal progenitor cells; cyclinD1; p27(Kip1); nuclear receptor; cell proliferation; vasculogenesis;
D O I
10.1523/JNEUROSCI.2235-04.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Tlx belongs to a class of orphan nuclear receptors that underlies many aspects of neural development in the CNS. However, the fundamental roles played by Tlx in the control of eye developmental programs remain elusive. By using Tlx knock-out ( KO) mice, we show here that Tlx is expressed by retinal progenitor cells in the neuroblastic layer during the period of retinal layer formation, and it is critical for controlling the generation of appropriate numbers of retinal progenies through the activities of cell cycle-related molecules, cyclin D1 and p27(Kip1). Tlx expression is restricted to Muller cells in the mature retina and appears to control their proper development. Furthermore, we show that Tlx is expressed by immature astrocytes that migrate from the optic nerve onto the inner surface of the retina and is required for their generation and maturation, as assessed by honeycomb network formation and expression of R-cadherin, a critical component for vasculogenesis. The impaired astrocyte network formation on the inner retinal surface is accompanied by the loss of vasculogenesis in Tlx KO retinas. Our studies thus indicate that Tlx underlies a fundamental developmental program of retinal organization and controls the generation of the proper numbers of retinal progenies and development of glial cells during the protracted period of retinogenesis.
引用
收藏
页码:8124 / 8134
页数:11
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