The Journal of Neuroscience, April 15, 2000, 20(8):2887-2895
Trk C Signaling Is Required for Retinal Progenitor Cell
Proliferation
Indranil
Das1,
Janet R.
Sparrow3,
Michelle I.
Lin1,
Evangeline
Shih1,
Takashi
Mikawa2, and
Barbara L.
Hempstead1
Departments of 1 Medicine and 2 Cell
Biology, Weill Medical College of Cornell University, New York, New
York 10021, and 3 Columbia University, Department of
Ophthalmology, New York, New York 10032
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.
Key words:
retina; NT-3; trk C; truncated trk C; retrovirus; chick; mitogen
Copyright © 2000 Society for Neuroscience 0270-6474/00/2082887-09$05.00/0
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