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Curr Biol. 2013 Mar 4;23(5):412-8. doi: 10.1016/j.cub.2013.01.046. Epub 2013 Feb 14.

Retinoid acid specifies neuronal identity through graded expression of Ascl1.

Author information

1
Division of Developmental Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. jjacob@nimr.mrc.ac.uk

Erratum in

  • Curr Biol. 2013 Apr 8;23(7):632. Kageyama, Ryoichoro [corrected to Kageyama, Ryoichiro].

Abstract

Cell diversity and organization in the neural tube depend on the integration of extrinsic signals acting along orthogonal axes. These are believed to specify distinct cellular identities by triggering all-or-none changes in expression of combinations of transcription factors. Under the influence of a common dorsoventral signal, sonic hedgehog, and distinct anterior-posterior (A-P) inductive signals, two topographically related progenitor pools that share a common transcriptional code produce serotonergic and V3 neurons in the hindbrain and spinal cord, respectively. These neurons have different physiological properties, functions, and connectivity. Serotonergic involvement in neuropsychiatric diseases has prompted greater characterization of their postmitotic repertoire of fate determinants, which include Gata2, Lmx1b, and Pet1, whereas V3 neurons express Sim1. How distinct serotonergic and V3 neuronal identities emerge from progenitors that share a common transcriptional code is not understood. Here, we show that changes in retinoid activity in these two progenitor pools determine their fates. Retinoids, via Notch signaling, control the expression level in progenitors of the transcription factor Ascl1, which selects serotonergic and V3 neuronal identities in a dose-dependent manner. Therefore, quantitative differences in the expression of a single component of a transcriptional code can select distinct cell fates.

PMID:
23416099
PMCID:
PMC3659286
DOI:
10.1016/j.cub.2013.01.046
[Indexed for MEDLINE]
Free PMC Article

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