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X.-J. Yang, Z. M. Verney; Dynamic Expression of bHLH Protein Neurogenin2 and Its Contribution to Retinal Cell Fates During Development. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4461.
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Accumulating evidence support that retinal progenitor cells are heterogeneous and undergo intrinsic changes that affect their competence to differentiate into various neuronal cell types. The progenitor competent states are in part represented by the complement of transcription factors expressed by a given cell. Previous studies have shown that transcripts of the bHLH transcription factor Neurogenin 2 (Ngn2) are expressed by a subset of retinal cells, and misexpression of Ngn2 promotes neurogenesis from cultured retinal pigment epithelial cells. This study examines the distribution of Ngn2 protein among progenitor cells and postmitotic neurons and determine the contribution of Ngn2-expressing progenitor cells to various retinal cell types.
In situ hybridization was used to examine the temporal expression profiles of Ngn2 mRNAs in the developing chicken and mouse retinas. Confocal and conventional immunofluorescent imaging studies with antibodies against Ngn2 and different retinal cell types were carried out using embryonic chicken retinal tissues. A 7kb Ngn2 promoter fragment driving the LacZ reporter gene was used to transfect retinal cells. Quantitative retinal cell marker analyses were performed to trace the cell fates of Ngn2-expressing cells.
Ngn2 mRNA is expressed by a subset of early retinal cells in the chicken and mouse retinas. Co-immunostaining of Ngn2 and other cell type markers indicates that Ngn2 protein is expressed predominantly by proliferating progenitor cells. Ngn2 protein is detected among cells undergoing S-phase and M-phase of the cell cycle. However, it is quickly down regulated in postmitotic neurons. In vitro lacZ reporter lineage tracing shows that Ngn2-expressing progenitor cells contribute to several early born neuronal cell types and new proliferating progenitors.
Ngng2 protein is expressed by a subset of early progenitor cells and is dynamically regulated during retinogenesis with regard to cell cycle. Ngn2-expressing progenitor cells are competent to differentiate into multiple neuronal cell types as well as contribute to later progenitor cells that renter the cell cycle.
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