title: Novel genes upregulated when NOTCH signalling is disrupted during hypothalamic development.
abstract: BACKGROUND
  The generation of diverse neuronal types and subtypes from multipotent progenitors during development is crucial for assembling functional neural circuits in the adult central nervous system. It is well known that the Notch signalling pathway through the inhibition of proneural genes is a key regulator of neurogenesis in the vertebrate central nervous system. However, the role of Notch during hypothalamus formation along with its downstream effectors remains poorly defined.
  
  
  RESULTS
  Here, we have transiently blocked Notch activity in chick embryos and used global gene expression analysis to provide evidence that Notch signalling modulates the generation of neurons in the early developing hypothalamus by lateral inhibition. Most importantly, we have taken advantage of this model to identify novel targets of Notch signalling, such as Tagln3 and Chga, which were expressed in hypothalamic neuronal nuclei.
  
  
  CONCLUSIONS
  These data give essential advances into the early generation of neurons in the hypothalamus. We demonstrate that inhibition of Notch signalling during early development of the hypothalamus enhances expression of several new markers. These genes must be considered as important new targets of the Notch/proneural network.
authors.forename: Leslie
authors.initials: L
authors.lastname: Ratié
authors.forename: Michelle
authors.initials: M
authors.lastname: Ware
authors.forename: Frédérique
authors.initials: F
authors.lastname: Barloy-Hubler
authors.forename: Hélène
authors.initials: H
authors.lastname: Romé
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gicquel
authors.forename: Christèle
authors.initials: C
authors.lastname: Dubourg
authors.forename: Véronique
authors.initials: V
authors.lastname: David
authors.affiliation: Institut de Génétique et Développement de Rennes, CNRS UMR6290, Université de Rennes 1, IFR140 GFAS, Faculté de Médecine, Rennes, France. valerie.dupe@univ-rennes1.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dupé
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D007031:Hypothalamus / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases