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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dhomen
Nathalie S
NS
Developmental Biology Unit, Institute of Child Health, London, UK.
Balaggan
Kam S
KS
Pearson
Rachael A
RA
Bainbridge
James W
JW
Levine
Edward M
EM
Ali
Robin R
RR
Sowden
Jane C
JC
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002924:Ciliary Body / Q000166:cytology / Q000378:metabolism; D004261:DNA Replication; D047108:Embryonic Development; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D018398:Homeodomain Proteins / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000502:physiology*
D015415:Biomarkers; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C088975:Vsx2 protein, mouse