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Dr Patricia Jusuf

Dr Patricia Jusuf

Postdoctoral Fellow, Department of Physiology, Development and Neuroscience, Cambridge University

Ptf1a (Pancreas transcription factor 1a) induces inhibitory neurons whose subtype depends on the excitatory lineages from which they arise in the developing retina

During neurogenesis of the central nervous system (CNS), a multitude of different neuronal types arise from multipotent progenitor cells. Differental gene expression helps co-ordinate these fates. The pancreas transcription factor 1a (Ptf1a) has been implicated in the determination of inhibitory fates throughout different CNS areas. Using a transgenic ptf1a:GFP line, Dr Jusuf shows that Ptf1a is expressed transiently after the terminal division of progenitors in all differentiating inhibitory neurons of the retina (3 types of horizontal cells and 28 types of amacrine cells).

Intriguingly, time-lapse and lineage studies using transgenic lines reporting the expression of previously described fate determination genes of excitatory cell types, revealed that ptf1a turns on in cells that arise from different parallel excitatory fates, and that the original lineage in which ptf1a expression turns on is a predictor of the subtype fate of the inhibitory neurons that arise from these lineages.  This suggests that the existence of factors that influence subtype specification are restricted to particular lineages and that it is the combination of Ptf1a and these factors that determine inhibitory subtype identity. The model arising from these data for the first time summarises the lineage relationship between excitatory neurons (that arise from parallel pools of lineage restricted progenitors) and inhibitory neurons (that arise from a second sequential pool after the last progenitor division) in the retina.

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