TY - JOUR
T1 - Roles of cell-intrinsic and microenvironmental factors in photoreceptor cell differentiation
AU - Bradford, Rebecca L.
AU - Wang, Chenwei
AU - Zack, Donald J.
AU - Adler, Ruben
N1 - Funding Information:
This work was supported by NIH grants EYO4859 (RA), EY 09769 (DJZ), and Core Grant EY1765, a center grant from the Foundation Fighting Blindness (Baltimore, MD), a grant from the Macula Vision Foundation, an unrestricted departmental grant from Research to Prevent Blindness, Inc. (New York, NY), and by funds from Mr. and Mrs. Robert and Clarice Smith. RA is the Arnall Patz Distinguished Professor of Ophthalmology, and a senior investigator of Research to Prevent Blindness, Inc. DJZ is the Guerrieri Professor of Genetic Engineering and Molecular Ophthalmology.
PY - 2005/10/1
Y1 - 2005/10/1
N2 - Photoreceptor differentiation requires the coordinated expression of numerous genes. It is unknown whether those genes share common regulatory mechanisms or are independently regulated by distinct mechanisms. To distinguish between these scenarios, we have used in situ hybridization, RT-PCR, and real-time PCR to analyze the expression of visual pigments and other photoreceptor-specific genes during chick embryo retinal development in ovo, as well as in retinal cell cultures treated with molecules that regulate the expression of particular visual pigments. In ovo, onset of gene expression was asynchronous, becoming detectable at the time of photoreceptor generation (ED 5-8) for some photoreceptor genes, but only around the time of outer segment formation (ED 14-16) for others. Treatment of retinal cell cultures with activin, staurosporine, or CNTF selectively induced or down-regulated specific visual pigment genes, but many cognate rod- or cone-specific genes were not affected by the treatments. These results indicate that many photoreceptor genes are independently regulated during development, are consistent with the existence of at least two distinct stages of gene expression during photoreceptor differentiation, suggest that intrinsic, coordinated regulation of a cascade of gene expression triggered by a commitment to the photoreceptor fate is not a general mechanism of photoreceptor differentiation, and imply that using a single photoreceptor-specific "marker" as a proxy to identify photoreceptor cell fate is problematic.
AB - Photoreceptor differentiation requires the coordinated expression of numerous genes. It is unknown whether those genes share common regulatory mechanisms or are independently regulated by distinct mechanisms. To distinguish between these scenarios, we have used in situ hybridization, RT-PCR, and real-time PCR to analyze the expression of visual pigments and other photoreceptor-specific genes during chick embryo retinal development in ovo, as well as in retinal cell cultures treated with molecules that regulate the expression of particular visual pigments. In ovo, onset of gene expression was asynchronous, becoming detectable at the time of photoreceptor generation (ED 5-8) for some photoreceptor genes, but only around the time of outer segment formation (ED 14-16) for others. Treatment of retinal cell cultures with activin, staurosporine, or CNTF selectively induced or down-regulated specific visual pigment genes, but many cognate rod- or cone-specific genes were not affected by the treatments. These results indicate that many photoreceptor genes are independently regulated during development, are consistent with the existence of at least two distinct stages of gene expression during photoreceptor differentiation, suggest that intrinsic, coordinated regulation of a cascade of gene expression triggered by a commitment to the photoreceptor fate is not a general mechanism of photoreceptor differentiation, and imply that using a single photoreceptor-specific "marker" as a proxy to identify photoreceptor cell fate is problematic.
KW - Cell culture
KW - Chick embryo
KW - Differentiation
KW - Growth factors
KW - Photoreceptor
KW - Visual pigments
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U2 - 10.1016/j.ydbio.2005.07.002
DO - 10.1016/j.ydbio.2005.07.002
M3 - Article
C2 - 16120439
AN - SCOPUS:25844488967
SN - 0012-1606
VL - 286
SP - 31
EP - 45
JO - Developmental biology
JF - Developmental biology
IS - 1
ER -