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Ascl1 as a Novel Player in the Ptf1a Transcriptional Network for GA... |
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by: |
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Mazurier, Nicolas |
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Parain, Karine |
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Parlier, Damien |
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Pretto, Silvia |
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Hamdache, Johanna |
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Vernier, Philippe |
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Locker, Morgane |
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Bellefroid, Eric |
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Perron, Muriel |
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This article is from PLoS ONE[1], volume 9[2]. |
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Abstract |
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In contrast with the wealth of data involving bHLH and |
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homeodomain transcription factors in retinal cell type |
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determination, the molecular bases underlying |
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neurotransmitter subtype specification is far less |
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understood. Using both gain and loss of function analyses |
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in Xenopus, we investigated the putative implication of |
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the bHLH factor Ascl1 in this process. We found that in |
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addition to its previously characterized proneural |
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function, Ascl1 also contributes to the specification of |
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the GABAergic phenotype. We showed that it is necessary |
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for retinal GABAergic cell genesis and sufficient in |
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overexpression experiments to bias a subset of retinal |
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precursor cells towards a GABAergic fate. We also |
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analysed the relationships between Ascl1 and a set of |
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other bHLH factors using an in vivo ectopic neurogenic |
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assay. We demonstrated that Ascl1 has unique features as |
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a GABAergic inducer and is epistatic over factors endowed |
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with glutamatergic potentialities such as Neurog2, |
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NeuroD1 or Atoh7. This functional specificity is |
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conferred by the basic DNA binding domain of Ascl1 and |
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involves a specific genetic network, distinct from that |
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underlying its previously demonstrated effects on |
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catecholaminergic differentiation. Our data show that |
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GABAergic inducing activity of Ascl1 requires the direct |
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transcriptional regulation of Ptf1a, providing therefore |
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a new piece of the network governing neurotransmitter |
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subtype specification during retinogenesis. |
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References |
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1. //archive.org/search.php?query=journaltitle%3A%28PLoS%20ONE%29 (link) |
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2. //archive.org/search.php?query=journaltitle%3A%28PLoS%20ONE%29%20AND%20volu… |
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Date Published: 2014-10-23 22:53:57 |
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Identifier: pubmed-PMC3958475 |
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Item Size: 42422988 |
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Language: eng |
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Media Type: texts |
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