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PMID: 16384989 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Absence of chx10 causes neural progenitors to persist in the adult retina.

Investigative ophthalmology & visual science ·Vol. 47 ·No. 1 ·2006-01-00 ·Pages 386-96

Dhomen NS, Balaggan KS, Pearson RA, Bainbridge JW, Levine EM, Ali RR, Sowden JC

Abstract

Mutation of the Chx10 homeobox gene in mice and humans causes congenital blindness and microphthalmia (small eyes). This study used Chx10-/- (ocular retardation) mice to investigate how lack of Chx10 affects progenitor/stem cell behavior in the retina and ciliary epithelium (CE). The distribution of mitotic retinal progenitor cells (RPCs) during embryonic development was analyzed using phosphohistone 3 (H3)-labeling. DNA flow cytometry was used to measure DNA content. The distribution and phenotype of dividing cells in the postnatal retina and CE was analyzed by incorporation of the thymidine analogue BrdU and immunohistochemistry. The Chx10-/- embryonic retina maintained a constantly sized population of mitotic RPCs during development, causing the mitotic index to increase markedly over time compared with the wild type. Also, the proportion of cells in the G1 phase of the cell cycle was increased compared with the wild type. Of interest, division of RPC-like cells with neurogenic properties persisted in the adult Chx10-/- retina. Colabeling for BrdU and the neural progenitor marker nestin or the neuronal markers beta3-tubulin, syntaxin, and VC1.1 showed that new amacrine-like neurons developed in the adult central retina. By contrast, cells with these characteristics were not observed in the mature wild-type retina. In the mature CE, BrdU-positive cells were observed in both wild-type and Chx10-/- mice. However, neurogenesis from this cell population was not evident. Without Chx10, proliferative expansion of the embryonic RPC pool is markedly reduced. In the adult retina, lack of Chx10 results in a population of dividing neural progenitor cells that persist and produce new neurons in the central retina.

MeSH Terms
Animals Apoptosis Biomarkers/metabolism Cell Cycle Cell Proliferation Ciliary Body/cytology,metabolism DNA Replication Embryonic Development Flow Cytometry Fluorescent Antibody Technique, Indirect Homeodomain Proteins/physiology In Situ Nick-End Labeling Mice Mice, Mutant Strains Nerve Tissue Proteins/metabolism Neurons/cytology,metabolism Pigment Epithelium of Eye/cytology,metabolism Retina/cytology,embryology,metabolism Stem Cells/cytology,metabolism Transcription Factors/deficiency,physiology
Chemicals
Biomarkers Homeodomain Proteins Nerve Tissue Proteins Transcription Factors Vsx2 protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Dhomen Nathalie S
Developmental Biology Unit, Institute of Child Health, London, UK.
Balaggan Kam S
Pearson Rachael A
Bainbridge James W
Levine Edward M
Ali Robin R
Sowden Jane C
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Article Info
Journal
Investigative ophthalmology & visual science
Abbr.
Invest Ophthalmol Vis Sci
ISSN
0146-0404
DOI
10.1167/iovs.05-0428
Published
2006-01-00
Pages
386-96
Language
English
Region
United States
NLM ID
7703701
PMCID
PMC2423807
Subset
IM
Grants
NEI NIH HHS · R01 EY013760 · United States
NEI NIH HHS · EY013760 · United States
External Links
PubMed source DOI: 10.1167/iovs.05-0428 PMC Full Text View journal details
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