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Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2004 Sep 15; Vol. 24 (37), pp. 8124-34. - Publication Year :
- 2004
-
Abstract
- 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 p27Kip1. Tlx expression is restricted to Müller 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.
- Subjects :
- Animals
Apoptosis
Astrocytes metabolism
Cadherins biosynthesis
Cadherins genetics
Cell Count
Cell Cycle
Cell Cycle Proteins physiology
Cell Differentiation
Cell Movement
Cyclin D1 physiology
Cyclin-Dependent Kinase Inhibitor p27
Eye Abnormalities genetics
Eye Proteins biosynthesis
Eye Proteins genetics
Gene Expression Regulation, Developmental
Mice
Mice, Knockout
Neovascularization, Physiologic genetics
Neuroglia metabolism
Receptors, Cytoplasmic and Nuclear biosynthesis
Receptors, Cytoplasmic and Nuclear deficiency
Receptors, Cytoplasmic and Nuclear genetics
Retina embryology
Retina growth & development
Retinal Vessels embryology
Retinal Vessels growth & development
Tumor Suppressor Proteins physiology
Astrocytes cytology
Eye Proteins physiology
Neuroglia cytology
Receptors, Cytoplasmic and Nuclear physiology
Retina cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 24
- Issue :
- 37
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 15371513
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.2235-04.2004