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Article Dans Une Revue BMC Developmental Biology Année : 2007

Ptf1a triggers GABAergic neuronal cell fates in the retina.

Jean-Philippe Dullin
  • Fonction : Auteur
Morgane Locker
  • Fonction : Auteur
Mélodie Robach
Kristine A Henningfeld
  • Fonction : Auteur
Karine Parain
  • Fonction : Auteur
Solomon Afelik
  • Fonction : Auteur
Tomas Pieler
  • Fonction : Auteur
Muriel Perron

Résumé

BACKGROUND: In recent years, considerable knowledge has been gained on the molecular mechanisms underlying retinal cell fate specification. However, hitherto studies focused primarily on the six major retinal cell classes (five types of neurons of one type of glial cell), and paid little attention to the specification of different neuronal subtypes within the same cell class. In particular, the molecular machinery governing the specification of the two most abundant neurotransmitter phenotypes in the retina, GABAergic and glutamatergic, is largely unknown. In the spinal cord and cerebellum, the transcription factor Ptf1a is essential for GABAergic neuron production. In the mouse retina, Ptf1a has been shown to be involved in horizontal and most amacrine neurons differentiation. RESULTS: In this study, we examined the distribution of neurotransmitter subtypes following Ptf1a gain and loss of function in the Xenopus retina. We found cell-autonomous dramatic switches between GABAergic and glutamatergic neuron production, concomitant with profound defects in the genesis of amacrine and horizontal cells, which are mainly GABAergic. Therefore, we investigated whether Ptf1a promotes the fate of these two cell types or acts directly as a GABAergic subtype determination factor. In ectodermal explant assays, Ptf1a was found to be a potent inducer of the GABAergic subtype. Moreover, clonal analysis in the retina revealed that Ptf1a overexpression leads to an increased ratio of GABAergic subtypes among the whole amacrine and horizontal cell population, highlighting its instructive capacity to promote this specific subtype of inhibitory neurons. Finally, we also found that within bipolar cells, which are typically glutamatergic interneurons, Ptf1a is able to trigger a GABAergic fate. CONCLUSION: Altogether, our results reveal for the first time in the retina a major player in the GABAergic versus glutamatergic cell specification genetic pathway.

Dates et versions

hal-00283597 , version 1 (30-05-2008)

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Citer

Jean-Philippe Dullin, Morgane Locker, Mélodie Robach, Kristine A Henningfeld, Karine Parain, et al.. Ptf1a triggers GABAergic neuronal cell fates in the retina.. BMC Developmental Biology, 2007, 7, pp.110. ⟨10.1186/1471-213X-7-110⟩. ⟨hal-00283597⟩
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