Atrophy of Müller glia and photoreceptor cells in chick retina misexpressing cNSCL2.
OBJECTIVE
To investigate whether and how the basic helix-loop-helix (bHLH) gene cNSCL2 is involved in retinal development.


METHODS
cNSCL2, the chick homologue of human NSCL2, was isolated and sequenced. In situ hybridization was used to examine its spatial and temporal expression pattern in the retina. Replication-competent retrovirus RCAS was used to drive cNSCL2 misexpression in the developing chick retina, and the effect of the misexpression was analyzed.


RESULTS
Expression of cNSCL2 in the retina was restricted. Its mRNA was detected in amacrine and horizontal cells, but not in photoreceptor, bipolar, or ganglion cells. Retroviral-driven misexpression of cNSCL2 in the developing chick retina resulted in missing photoreceptor cells and gross deficits in the outer nuclear layer (ONL). These deficits were probably not because of decreased photoreceptor production, in that the ONL appeared normal in early developmental stages. TUNEL+ cells were detected in the ONL, indicating that photoreceptor cells underwent apoptosis in retinas misexpressing cNSCL2. Müller glial cells were far fewer in the experimental retina than in the control, indicating that cNSCL2 also caused Müller glia atrophy. The onset of Müller glia disappearance preceded that of photoreceptor degeneration.


CONCLUSIONS
Expression of cNSCL2 in the chick retina was restricted to amacrine and horizontal cells. Misexpression of cNSCL2 caused severe retinal degeneration, and photoreceptor cells and Müller glia were particularly affected.
Li
C M
CM
Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, 700 South 18th Street, Birmingham, AL 35294-0009, USA.
Yan
R T
RT
Wang
S Z
SZ
D000818:Animals; D001284:Atrophy; D002642:Chick Embryo / Q000033:anatomy & histology* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D005865:Gestational Age; D009457:Neuroglia / Q000473:pathology; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D012160:Retina / Q000196:embryology* / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology*; D017386:Sequence Homology, Amino Acid
D004268:DNA-Binding Proteins