Cadherins are a family of cell surface molecules mediating calcium-dependent cell-cell adhesion in a variety of tissues. More than a dozen cadherins are expressed in the vertebrate brain. To obtain insight into the biological significance of this diversity in cadherin expression, we mapped the expression of N- and R-cadherin in the brain of the developing chicken embryo (days 2-19 of incubation) by immunohistochemical and in situ hybridization techniques. Whereas the expression of N- and R-cadherin is relatively uniform or weak in early (about 2-5 days of incubation) and late development (15 days of incubation to hatching stage), these two molecules are differentially expressed in specific nuclei and fiber tracts between days 6-11 of incubation. For example, in the mes- and diencephalon, one of the tectofugal pathways and its target nuclei, here called the tecto-pretecto-rotundal system, express N-cadherin. R-cadherin is expressed by a different tectofugal system, the tectoisthmic pathway. The other tectofugal systems express neither N- nor R-cadherin. In addition, a small number of other mes- and diencephalic nuclei express N- or R-cadherin. On the basis of these results and experimental evidence from other studies, we speculate that the two cadherins are involved in the formation and segregation of particular functional systems within the vertebrate central nervous system (CNS) by regulating the formation of nuclei, and the pathfinding and/or the selective fasciculation of neurites. Apart from neuronal elements, a variety of vascular and ependymal structures also express N-cadherin or R-cadherin, e.g., the parenchymal blood vessels, the choroid plexus, the floor and roof plates, and the ventricular lining. These findings suggest that the two cadherins play a variety of roles during the development of neuronal and nonneuronal epithelial structures throughout CNS development.
Stimulated by evidence implicating diurnal/circadian rhythms and light in refractive development, we studied the expression over 24 hours of selected clock and circadian rhythm-related genes in retina/retinal pigment epithelium (RPE) and choroid of experimental ametropias in chicks. METHODS. Newly hatched chicks, entrained to a 12-hour light/dark cycle for 12 to 14 days, either experienced nonrestricted vision OU (i.e., in both eyes) or received an imageblurring diffuser or a minus 10-diopter (D) or a plus 10-D defocusing lens over one eye. Starting 1 day later and at 4-hour intervals for 24 hours, the retina/RPE and choroid were separately dissected. Without pooling, total RNA was extracted, converted to cDNA, and assayed by quantitative PCR for the expression of the following genes: Opn4m, Clock, Npas2, Per3, Cry1, Arntl, and Mtnr1a. RESULTS. The expression of each gene in retina/RPE and in choroid of eyes with nonrestricted vision OU varied over 24 hours, with equal levels OU for most genes and times. Altered visual input influenced gene expression in complex patterns that varied by gene, visual input, time, and eye, affecting experimental eyes with altered vision and also contralateral eyes with nonrestricted vision. DISCUSSION. Altering visual input in ways known to induce ametropias alters the retinal/RPE and choroidal expression of circadian rhythm-related genes, further linking circadian biology with eye growth regulation. While further investigations are needed, studying circadian processes may help understand refractive mechanisms and the increasing myopia prevalence in contemporary societies where lighting patterns can desynchronize endogenous rhythms from the natural environmental light/dark cycle.
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