Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina

Centre de Recherche des Cordeliers, INSERM UMR S872, 75006 Paris, France.
Developmental Biology (Impact Factor: 3.55). 07/2011; 358(2):296-308. DOI: 10.1016/j.ydbio.2011.07.033
Source: PubMed


During development, progenitor cells of the retina give rise to six principal classes of neurons and the Müller glial cells found within the adult retina. The pancreas transcription factor 1 subunit a (Ptf1a) encodes a basic-helix-loop-helix transcription factor necessary for the specification of horizontal cells and the majority of amacrine cell subtypes in the mouse retina. The Ptf1a-regulated genes and the regulation of Ptf1a activity by transcription cofactors during retinogenesis have been poorly investigated. Using a retrovirus-mediated gene transfer approach, we reported that Ptf1a was sufficient to promote the fates of amacrine and horizontal cells from retinal progenitors and inhibit retinal ganglion cell and photoreceptor differentiation in the chick retina. Both GABAergic H1 and non-GABAergic H3 horizontal cells were induced following the forced expression of Ptf1a. We describe Ptf1a as a strong, negative regulator of Atoh7 expression. Furthermore, the Rbpj-interacting domains of Ptf1a protein were required for its effects on cell fate specification. Together, these data provide a novel insight into the molecular basis of Ptf1a activity on early cell specification in the chick retina.

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Available from: Jean-Marc Matter,
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    • "Vsx2 downregulation also de-represses FoxN4, which turns on Ptf1a, a TF that is necessary and sufficient for the generation of amacrine cells (ACs) and horizontal cells (HCs), and is capable of overriding Atoh7's GC-promoting activity (Dullin et al., 2007; Fujitani et al., 2006; Jusuf et al., 2011; Leliè vre et al., 2011; Vitorino et al., 2009). Some Ptf1a expressing cells co-express Lhx1, and these adopt HC fates (Boije et al., 2013; Leliè vre et al., 2011). Other cells, released from Vsx2 repression, express Vsx1 and give rise to the majority of bipolar cells (BCs) in the zebrafish retina (Chow et al., 2001; Ohtoshi et al., 2001; Vitorino et al., 2009). "
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    • "Our previous studies and others highlighted that the bHLH gene Ptf1a (pancreas transcription factor 1a), drives inhibitory neuron commitment in the retina, at the expense of a glutamatergic destiny [39], [40], [41], [42], [43]. However, upstream regulators, partners and targets of Ptf1a within the retina remain to be investigated. "
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