title: The ciliogenic transcription factor Rfx3 is required for the formation of the thalamocortical tract by regulating the patterning of prethalamus and ventral telencephalon.
abstract: Primary cilia are complex subcellular structures that play key roles during embryogenesis by controlling the cellular response to several signaling pathways. Defects in the function and/or structure of primary cilia underlie a large number of human syndromes collectively referred to as ciliopathies. Often, ciliopathies are associated with mental retardation (MR) and malformation of the corpus callosum. However, the possibility of defects in other forebrain axon tracts, which could contribute to the cognitive disorders of these patients, has not been explored. Here, we investigate the formation of the corticothalamic/thalamocortical tracts in mice mutant for Rfx3, which regulates the expression of many genes involved in ciliogenesis and cilia function. Using DiI axon tracing and immunohistochemistry experiments, we show that some Rfx3(-/-) corticothalamic axons abnormally migrate toward the pial surface of the ventral telencephalon (VT). Some thalamocortical axons (TCAs) also fail to leave the diencephalon or abnormally project toward the amygdala. Moreover, the Rfx3(-/-) VT displays heterotopias containing attractive guidance cues and expressing the guidance molecules Slit1 and Netrin1. Finally, the abnormal projection of TCAs toward the amygdala is also present in mice carrying a mutation in the Inpp5e gene, which is mutated in Joubert Syndrome and which controls cilia signaling and stability. The presence of identical thalamocortical malformations in two independent ciliary mutants indicates a novel role for primary cilia in the formation of the corticothalamic/thalamocortical tracts by establishing the correct cellular environment necessary for its development.
authors: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, UK.
authors: Dario
authors: D
authors: Magnani
authors: Centre de Génétique et de Physiologie Moléculaires et Cellulaires, CNRS UMR 5534, Université Claude Bernard Lyon 1, Villeurbanne, Lyon F69622, France.
authors: Laurette
authors: L
authors: Morlé
authors: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, UK.
authors: Kerstin
authors: K
authors: Hasenpusch-Theil
authors: Centre de Génétique et de Physiologie Moléculaires et Cellulaires, CNRS UMR 5534, Université Claude Bernard Lyon 1, Villeurbanne, Lyon F69622, France.
authors: Marie
authors: M
authors: Paschaki
authors: Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, Luxembourg, Luxembourg and.
authors: Monique
authors: M
authors: Jacoby
authors: Laboratory of Functional Genetics, GIGA-Signal Transduction, GIGA B34, Université de Liège, Liège B-4000, Belgium.
authors: Stéphane
authors: S
authors: Schurmans
authors: Centre de Génétique et de Physiologie Moléculaires et Cellulaires, CNRS UMR 5534, Université Claude Bernard Lyon 1, Villeurbanne, Lyon F69622, France.
authors: Bénédicte
authors: B
authors: Durand
authors: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, UK, thomas.theil@ed.ac.uk.
authors: Thomas
authors: T
authors: Theil
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004622:Embryo, Mammalian; D006720:Homozygote; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways; D009474:Neurons / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D013788:Thalamus / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D000074290:Zinc Finger Protein Gli3; D000099182:Phosphoinositide 5-Phosphatases
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D010744:Phosphoric Monoester Hydrolases; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3; D000099182:Phosphoinositide 5-Phosphatases; C465571:Gli3 protein, mouse; C000605540:RFX3 protein, human; C000605541:Rfx3 protein, mouse