title: Ascl1 as a novel player in the Ptf1a transcriptional network for GABAergic cell specification in the retina.
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.
authors.affiliation: UPR Centre national de la recherche scientifique 3294 Neurobiology and Development, University Paris Sud, Orsay, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mazurier
authors.affiliation: UPR Centre national de la recherche scientifique 3294 Neurobiology and Development, University Paris Sud, Orsay, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Parain
authors.affiliation: ULB-IBMM, Laboratoire d'Embryologie Moléculaire, Gosselies, Belgium.
authors.forename: Damien
authors.initials: D
authors.lastname: Parlier
authors.affiliation: UPR Centre national de la recherche scientifique 3294 Neurobiology and Development, University Paris Sud, Orsay, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pretto
authors.affiliation: UPR Centre national de la recherche scientifique 3294 Neurobiology and Development, University Paris Sud, Orsay, France.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hamdache
authors.affiliation: UPR Centre national de la recherche scientifique 3294 Neurobiology and Development, Institut A. Fessard, Gif-Sur-Yvette, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vernier
authors.affiliation: UPR Centre national de la recherche scientifique 3294 Neurobiology and Development, University Paris Sud, Orsay, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Locker
authors.affiliation: ULB-IBMM, Laboratoire d'Embryologie Moléculaire, Gosselies, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Bellefroid
authors.affiliation: UPR Centre national de la recherche scientifique 3294 Neurobiology and Development, University Paris Sud, Orsay, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Perron
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D018079:Receptors, GABA; D029867:Xenopus Proteins; D005680:gamma-Aminobutyric Acid; C581699:Ptf1a protein, Xenopus; C080088:ascl1 protein, Xenopus