Trk C signaling is required for retinal progenitor cell proliferation

被引:0
|
作者
Das, I
Sparrow, JR
Lin, MI
Shih, E
Mikawa, T
Hempstead, BL
机构
[1] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA
[2] Cornell Univ, Weill Med Coll, Dept Cell Biol, New York, NY 10021 USA
[3] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA
来源
JOURNAL OF NEUROSCIENCE | 2000年 / 20卷 / 08期
关键词
retina; NT-3; trk C; truncated trk C; retrovirus; chick; mitogen;
D O I
暂无
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Although neurotrophin actions in the survival of specific retinal cell types have been identified, the biological functions for neurotrophin-3 (NT-3) in early retinal development remain unclear. Having localized NT-3 and trk C expression at early developmental stages when retinal neuroepithelial progenitor cells predominate, we sought to modulate NT-3 signaling in these cells by overexpressing a truncated isoform of the NT-3 receptor, trk C. We have demonstrated that this non-catalytic receptor can inhibit NT-3 signaling when coexpressed with the full-length kinase-active trk C receptor. Using a replication-deficient retrovirus to ectopically express the truncated trk C receptor to limited numbers of progenitor cells in ovo, we examined the effects of disrupted trk C signaling on the proliferation or differentiation of retinal cells. Clones expressing truncated trk C exhibited a 70% reduction in clone size, compared with clones infected with a control virus, indicating that inhibition of trk C signaling decreased the clonal expansion of cells derived from a single retinal progenitor cell. Additionally, impaired NT-3 signaling resulted in a reduction of all retinal cell types, suggesting that NT-3 targets retinal precursor cells rather than differentiated cell types. BrdU labeling studies performed at E6 indicate that this reduction in cell number occurs through a decrease in cell proliferation. These studies suggest that NT-3 is an important mitogen early in retinal development and serves to establish the size of the progenitor pool from which all future differentiated cells arise.
引用
收藏
页码:2887 / 2895
页数:9
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