title: Retinoid acid specifies neuronal identity through graded expression of Ascl1.
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.
authors: Division of Developmental Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. jjacob@nimr.mrc.ac.uk
authors: John
authors: J
authors: Jacob
authors: Jennifer
authors: J
authors: Kong
authors: Steven
authors: S
authors: Moore
authors: Christopher
authors: C
authors: Milton
authors: Noriaki
authors: N
authors: Sasai
authors: Rosa
authors: R
authors: Gonzalez-Quevedo
authors: Javier
authors: J
authors: Terriente
authors: Itaru
authors: I
authors: Imayoshi
authors: Ryoichiro
authors: R
authors: Kageyama
authors: Ryoichoro
authors: R
authors: Kageyama
authors: David G
authors: DG
authors: Wilkinson
authors: Bennett G
authors: BG
authors: Novitch
authors: James
authors: J
authors: Briscoe
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002642:Chick Embryo; D051379:Mice; D008822:Mice, Transgenic; D054259:Neural Tube / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D055495:Neurogenesis; D051880:Receptors, Notch / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D059326:Serotonergic Neurons / Q000166:cytology; D015398:Signal Transduction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051880:Receptors, Notch; D012176:Retinoids; C499317:Ascl1 protein, mouse