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F. Hallbook, M. Lek, H. Boije, S. M. Myers-Lindback, P.-H. Edqvist; Axon-Bearing and Axon-Less Horizontal Cells Are Generated Consecutively During Chick Retinal Development From Progenitor Cells That Are Sensitive to Follistatin. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3557.
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Horizontal cells are retinal interneurons that modulate the output from photoreceptors. The purpose of this study was to outline the events that underlie the formation of horizontal cells. In most vertebrates including chicken, two main horizontal cell subtypes are identified based on the presence or absence of an axon.
We have used the chicken embryo for in ovo injections of agents in combination with subsequent histological analyses. Birth dating was performed using a combination of 3H-thymidine incorporation with markers for horizontal cell subtypes.
First we molecularly characterized three horizontal cell subtypes based on Lim1, Isl1, GABA and TrkA, a classification that is consistent with at least three chick horizontal subtypes previously defined by morphology. The axon-bearing and axon-less horizontal cell subpopulations are molecularly defined by Lim1 and Isl1, are born consecutively at embryonic day (E) 3-4 and E4-5, respectively, and exhibit temporally distinguishable periods of migration. Their relative numbers are not adjusted by apoptosis. A sharp decrease of high endogenous mRNA levels of the activin-inhibitor follistatin, at E3 coincides with the appearance of the Lim1 positive cells. Extending the follistatin exposure of the horizontal cell retinal progenitor cells by injections of follistatin at E3, increased the number of both Lim1- and Isl1-positive horizontal cells when analysed at E9.
The results imply that the axon-bearing and axon-less horizontal cell subgroups are defined early and are generated consecutively from a retinal progenitor cell population that is sensitive to the inhibitory action of follistatin. The results are consistent with a model wherein added follistatin cause horizontal cell generating progenitors to proliferate beyond the normal period of horizontal cell generation, thus producing extra cells of both types that later migrate to the horizontal cell layer next to the outer plexiform layer.
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