DIFFERENTIAL REGULATION OF CILIARY NEUROTROPHIC FACTOR RECEPTOR-ALPHAEXPRESSION IN ALL MAJOR NEURONAL CELL CLASSES DURING DEVELOPMENT OF THE CHICK RETINA

Ciliary neurotrophic factor (CNTF) exerts a multiplicity of effects on a broad spectrum of target cells, including retinal neurons. To inves tigate how this functional complexity relates to the regulation of CNT F receptor a: (CNTFR alpha) expression, we have studied the developmen tal expression of the receptor protein in chick retina by using immuno cytochemistry. During the course of development, the receptor is expre ssed in all retinal layers, but three levels of specificity can be obs erved. First, the expression is regulated temporally with immunoreacti vity observed in ganglion cells (embryonic day 8 [E8] to adult), photo receptor precursors (E8-E12), amacrine cells (E10 to adult), bipolar c ells (E12-E18), differentiated rods (E18 to adult), and horizontal cel ls (adult). Second, expression is restricted to distinct subpopulation s of principal retinal neurons: preferentially, large ganglion cells; subpopulation; of amacrine cells, including a particular type of choli nergic neuron; a distinctly located type of bipolar cell; and rod phot oreceptors. Third, expression exhibits subcellular restriction: it is confined largely to dendrites in mature amacrine cells and is restrict ed entirely to outer segments in mature rods. These data correlate wit h CNTF effects on the survival of ganglion cells and mature photorecep tors, the in vitro differentiation of photoreceptor precursors and cho linergic amacrine cells, and the number of bipolar cells in culture de scribed here or in previous studies. Thus, our results demonstrate an exceptional degree of complexity with respect to the regulation of neu ronal CNTFR alpha expression in a defined model system. This suggests that the same signaling pathway is used to mediate a variety of regula tory influences, depending on the developmental stage and cell type. ( C) 1998 Wiley-Liss, Inc.