Initial cholinergic differentiation in embryonic chick retina is responsive to insulin and cell-cell interactions.
Previous work [Kyriakis et al., Proc. Natl. Acad. Sci. U.S.A., 84 (1987) 7463-7467] had shown that insulin, when added during a window of binding from embryonic days 9-11, stimulates the normal developmental increase in choline acetyltransferase (ChAT) activity (a marker for cholinergic differentiation) in cultured embryonic chick retinal neurons. Here, we investigated the effect of insulin and IGF 1 on embryonic chick retinal neurons at the stage of development (embryonic day 6) when ChAT activity is first expressed. We investigated insulin peptide effects in retinal tissue developing in vitro as well as in cultures of retinal cells. We show that insulin also stimulated the initial embryonic increase in ChAT activity but had no stimulatory effect on glutamic acid decarboxylase activity (a marker for GABAergic differentiation), an enzyme whose activity also increases developmentally in the same retinal neurons. In fact, insulin inhibited the expression of GAD activity in the retina. The insulin-mediated increase in ChAT activity was independent of normal cell-cell interactions but could not replace them. Insulin also stimulated choline uptake but only after a two day delay, suggesting that the normal program for cholinergic differentiation in the chick retina was induced by insulin. IGF 1 did not have any effect on either cholinergic or GABAergic differentiation. We conclude that cholinergic differentiation in chick embryo retinal neurons is dependent on both insulin- and cell contact-mediated signals.
Hausman
R E
RE
Department of Biology, Boston University, MA 02215.
Sagar
G D
GD
Shah
B H
BH
D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002642:Chick Embryo; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D012160:Retina / Q000166:cytology* / Q000201:enzymology
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase