Blog
About

51
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Poster: found
      Is Open Access

      PAX6: a transcriptional guardian for glutamatergic fate in the developing neocortex

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          During forebrain development, the transcription factor PAX6 is highly expressed by progenitors in the dorsal telencephalon (dTel) i.e. the primitive cerebral cortex with a sharp boundary at the pallial-subpallial boundary, thereby establishing the dorso-ventral patterning of the forebrain and regulating the generation of cortical glutamatergic neurons. Strikingly, removal of Pax6led to a diversion away from the glutamatergic identity in a subset of cortical progenitors indicated by ectopic gene expression. We postulate that PAX6 confers glutamatergic fate in progenitors by preventing them from responding to signaling cues such as SHH that can induce abberant fates. In the present study, we used the transgenic mouse model with Pax6conditionally deleted in the cortex using a tamoxifen-inducible Emx1-CreER T2 transgene combined with a floxed Pax6and an EGFP constructs. Single-cell transcriptome revealed multiple ectopic leanages in cortical progenitors with morphogen-regulated transcriptional signatures upon Pax6deletion. We also undertook a candidate approach to investigate how attenuation of signaling cues by surgical and pharmacological means using in vitroslice culture affect the magnitude of ectopic gene expression in the cortical progenitors. We demonstrated that attenuation of interneuron migration into the cortex and inhibition of SHH signaling pathway in slice culture substatially reduced aberrant gene expression in the cortical progenitors. Our findings suggest that ventral cues from vTel such as SHH possess ventralizing effect on cortical progenitors, this is consistent with a requirement for PAX6 to resist such effects in order to safeguard glutamatergic fate.

          Related collections

          Author and article information

          Journal
          ScienceOpen Posters
          ScienceOpen
          10 July 2020
          Affiliations
          [1 ] Centre for Discovery Brain Sciences (CDBS), University of Edinburgh, Edinburgh, United Kingdom.
          Article
          10.14293/S2199-1006.1.SOR-.PPKAD1S.v1

          This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

          Comments

          Comment on this article