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Y. Elshatory, M. Deng, X. Xie, L. Gan; Expression of the LIM-Homeodomain Protein Isl1 in Developing Mouse Retina: Evidence for a Role in the Neuronal Differentiation of Retinal Bipolar, Amacrine and Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5682.
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© ARVO (1962-2015); The Authors (2016-present)
The mammalian retina is comprised of six major neuronal cell types and is subdivided into more morphological and physiological subtypes. The transcriptional machinery underlying these subtype fate choices is largely unknown. The LIM-homeodomain protein, Isl1, plays an essential role in CNS differentiation and in the establishment of neuronal diversity, but its function in retinal neurogenesis remains unknown. Our objective was to characterize the expression of Isl1 throughout neurogenesis, and identify its potential roles by so doing.
Using co-immunolabeling techniques, the expression of Isl1 in developing and mature C57BL/6J mouse retina is gauged relative to known cell-type specific markers for various retinal neurons, as well as other known transcriptional regulators of retinal neuron differentiation.
We report here Isl1's dynamic spatiotemporal expression in mouse retina and suggest its role in the formation of ganglion, cholinergic amacrine, and ON-bipolar cells based on its early expression in the ontogeny of these major neuronal cell types. Among bipolar interneurons, Isl1 expression commences at postnatal day 5 and is later restricted to ON-bipolar cells. The intensity of Isl1 expression is found to segregate the pool of ON-bipolar cells into rod and ON-cone bipolar cells with higher expression in rod bipolars. As bipolar cell development proceeds from postnatal day 5 to 10, the co-localization of Isl1 and the pan-bipolar cell marker Chx10 reveals the organization of ON-center bipolar cell nuclei to the upper portion of the inner nuclear layer. Further, whereas Isl1 is predominantly a ganglion cell marker prior to E15.5. At E15.5 and later, its expression in non-ganglion cells expands. We demonstrate that these Isl1-positive, non-ganglion cells acquire the expression of amacrine cell markers embryonically, likely representing nascent cholinergic amacrine cells.
Isl1 is expressed during the maturation of and is later maintained in retinal ganglion cells and subtypes of amacrine and bipolar cells where it may function in the maintenance of these cells into adulthood. The restriction of Isl1 to ON-bipolar cells, cholinergic amacrines, and retinal ganglion cells in the adult retina, along with its early expression within these cell types, suggests a potential role for Isl1 in ON-visual pathway development, cholinergic neuron differentiation, and retinal ganglion cell development.
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