Pathways of differentiation in chick embryo neuroretinal cultures.
Markers of neuronal cell differentiation (GABA accumulation, choline acetyltransferase activity) are shown to increase initially and then decline sharply in monolayer cultures of 9 day embryo neuroretinal (NR) cells. A glial marker (glutamine synthetase, GSase) is precociously inducible by hydrocortisone (HC) in dens "monolayer' NR cultures (containing aggregates of neuronal cells overlying the glian sheet) as well as in chick embryo retinal explants. The induced level of GSase activity is not maintained in the continued presence of HC, but rather declines by 20 days in vitro. Choline acetyltransferase (CAT) activity is higher in HC-treated cultures than in controls only during the period when induced GSase activity is detectable. Furthermore, the subsequent transdifferentiation of lens cells (monitored as delta crystalline content) in these cultures is delayed by 10 days and much reduced in extent when HC is present throughout the culture period. We suggest a simple model to account for these results, on the basis of recent evidence that lens cells are derived mainly from the retinal epithelial cells (immature Müller glia) of 9-day embryonic NR, and that transdifferentiation results from a change in cell determination during the early stages of "monolayers' culture. In outline, our model proposes that early determination of the retinal glia is associated with a decline of neuronal cell markers (dedifferentiation) followed eventually by loss of the neuronal cells. Hydrocortisone, by inducing transient glial cell differentiation (GSase activity), both prolongs the expression of a neuronal marker (CAT) and also reduces later transdifferentiation into lens.
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003459:Crystallins / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D007908:Lens, Crystalline / Q000166:cytology; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D003459:Crystallins; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D005974:Glutamate-Ammonia Ligase; D002794:Choline; D006854:Hydrocortisone