Axon-bearing and axon-less horizontal cell subtypes are generated consecutively during chick retinal development from progenitors that are sensitive to follistatin.
BACKGROUND
Horizontal cells are retinal interneurons that modulate the output from photoreceptors. A rich literature on the morphological classification and functional properties of HCs in different animals exists, however, the understanding of the events underlying their development is still limited. In most vertebrates including chicken, two main horizontal cell (HC) subtypes are identified based on the presence or absence of an axon.


RESULTS
In this work we have molecularly characterized three HC subtypes based on Lim1, Isl1, GABA and TrkA, a classification that is consistent with three chick HC subtypes previously defined by morphology. The axon-bearing and axon-less HC subpopulations molecularly defined by Lim1 and Isl1, are born consecutively on 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 levels of the activin-inhibitor follistatin at E3 coincides with the appearance of the Lim1 positive cells. Extending the follistatin exposure of the HC retinal progenitor cells by injection of follistatin at E3 increased the number of both Lim1- and Isl1 positive HCs when analysed at E9.


CONCLUSIONS
The results imply that the axon-bearing and axon-less HC 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 causes HC-generating progenitors to proliferate beyond the normal period of HC generation, thus producing extra HCs of both types that migrate to the HC layer.
Edqvist
Per-Henrik D
PH
Department of Neuroscience, Unit of Developmental Neuroscience, Biomedical Centre, Uppsala University, S-751 23, Uppsala, Sweden. per-henrik.edqvist@neuro.uu.se
Lek
Madelen
M
Boije
Henrik
H
Lindbäck
Sarah M
SM
Hallböök
Finn
F
D000818:Animals; D001369:Axons / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D038681:Follistatin / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D051248:Retinal Horizontal Cells / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors
D038681:Follistatin; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1