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XB-ART-48702
PLoS One January 1, 2014; 9 (3): e92113.

Ascl1 as a novel player in the Ptf1a transcriptional network for GABAergic cell specification in the retina.

Mazurier N , Parain K , Parlier D , Pretto S , Hamdache J , Vernier P , Locker M , Bellefroid E , Perron M .


Abstract
In contrast with the wealth of data involving bHLH and homeodomain transcription factors in retinal cell type determination, the molecular bases underlying neurotransmitter subtype specification is far less understood. Using both gain and loss of function analyses in Xenopus, we investigated the putative implication of the bHLH factor Ascl1 in this process. We found that in addition to its previously characterized proneural function, Ascl1 also contributes to the specification of the GABAergic phenotype. We showed that it is necessary for retinal GABAergic cell genesis and sufficient in overexpression experiments to bias a subset of retinal precursor cells towards a GABAergic fate. We also analysed the relationships between Ascl1 and a set of other bHLH factors using an in vivo ectopic neurogenic assay. We demonstrated that Ascl1 has unique features as a GABAergic inducer and is epistatic over factors endowed with glutamatergic potentialities such as Neurog2, NeuroD1 or Atoh7. This functional specificity is conferred by the basic DNA binding domain of Ascl1 and involves a specific genetic network, distinct from that underlying its previously demonstrated effects on catecholaminergic differentiation. Our data show that GABAergic inducing activity of Ascl1 requires the direct transcriptional regulation of Ptf1a, providing therefore a new piece of the network governing neurotransmitter subtype specification during retinogenesis.

PubMed ID: 24643195
PMC ID: PMC3958475
Article link: PLoS One

Genes referenced: ascl1 atoh7 dpysl3 gad1.2 hand2 myc neurod1 neurog2 phox2a ptf1a slc17a7 th tubb2b
Morpholinos: ascl1 MO1 ascl1 MO2 hand2 MO1 phox2a MO1 ptf1a MO3


Article Images: [+] show captions
References [+] :
Adler, Have we achieved a unified model of photoreceptor cell fate specification in vertebrates? 2008, Pubmed, Xenbase


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