[Primary cilia control different steps of brain development].
The role of primary cilia in adult neurons remains elusive, however their developmental functions during brain morphogenesis have been recently highlighted thanks to mouse models. Unmistakably, they are needed for Hedgehog (Hh)-dependent patterning in the forebrain. Not only for Hh reception itself, but most importantly for a downstream event in the Hh transduction pathway, independent of Hh ligand: the Gli3 processing. Indeed, phenotypes due to cilia disruption in the developing brain, such as early patterning, olfactory bulb or corpus callosum formation, can be rescued by reintroducing Gli3-R (the short truncated form of Gli3 working as a transcriptional repressor of Hh target gene). In addition, primary cilia control the proliferation rate in different neural progenitors in the cortex, the hippocampus and the cerebellum; they are required for proper migration of interneurons. And cilia dysfunction is correlated with hydrocephaly, synaptogenesis defects and aberrant axonal tract projections. Most of these neurodevelopmental defects can be related to the various neurological features frequently observed across the ciliopathy spectrum. And thus, understanding the underlying mechanisms of these diverse functions of primary cilia in the brain is a new fundamental challenge.
Laboratoire de biologie du développement, UPMC Université Paris 6, UMR 7622 CNRS, U969 Inserm, 9, quai Saint Bernard, 75005 Paris, France.
Christine
C
Laclef
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D001921:Brain / Q000002:abnormalities / Q000196:embryology* / Q000254:growth & development / Q000648:ultrastructure; D002455:Cell Division; D002465:Cell Movement; D016764:Cell Polarity; D002923:Cilia / Q000502:physiology*; D002925:Ciliary Motility Disorders / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D006849:Hydrocephalus / Q000235:genetics / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008322:Mammals; D051379:Mice; D009024:Morphogenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009421:Nervous System Malformations / Q000196:embryology / Q000235:genetics / Q000473:pathology; D054259:Neural Tube / Q000254:growth & development / Q000648:ultrastructure; D009436:Neural Tube Defects / Q000196:embryology / Q000235:genetics / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins