title: Celsr3 and Fzd3 Organize a Pioneer Neuron Scaffold to Steer Growing Thalamocortical Axons.
abstract: Celsr3 and Fzd3 regulate the development of reciprocal thalamocortical projections independently of their expression in cortical or thalamic neurons. To understand this cell non autonomous mechanism further, we tested whether Celsr3 and Fzd3 could act via Isl1-positive guidepost cells. Isl1-positive cells appear in the forebrain at embryonic day (E) 9.5-E10.5 and, from E12.5, they form 2 contingents in ventral telencephalon and prethalamus. In control mice, corticothalamic axons run in the ventral telencephalic corridor in close contact with Isl1-positive cells. When Celsr3 or Fzd3 is inactivated in Isl1-expressing cells, corticofugal fibers stall and loop in the ventral telencephalic corridor of high Isl1 expression, and thalamic axons fail to cross the diencephalon-telencephalon junction (DTJ). At E12.5, before thalamic and cortical axons emerge, pioneer projections from Isl1-positive cells cross the DTJ from both sides in control but not mutant embryos. These early projections appear to act like a bridge to guide later growing thalamic axons through the DTJ. Our data suggest that Celsr3 and Fzd3 orchestrate the formation of a scaffold of pioneer neurons and their axons. This scaffold extends from prethalamus to ventral telencephalon and subcortex, and steers reciprocal corticothalamic fibers.
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory Guangdong key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Feng
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory Guangdong key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.
authors.forename: Quanxiang
authors.initials: Q
authors.lastname: Xian
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory Guangdong key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Guan
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory Guangdong key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory Guangdong key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.
authors.forename: Meizhi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory Guangdong key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory Guangdong key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China Department of Anatomy, The University of Hong Kong Pokfulam, Hong Kong SAR, PR China.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Brussels B1200, Belgium.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Chai
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Brussels B1200, Belgium.
authors.forename: Andre M
authors.initials: AM
authors.lastname: Goffinet
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory Guangdong key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China Co-innovation Center of Neuroregeneration, Jiangsu, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory Guangdong key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China Co-innovation Center of Neuroregeneration, Jiangsu, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D000071446:Neuronal Outgrowth / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C444454:Celsr3 protein, mouse; C501120:Dlx5 protein, mouse; C100597:Dlx6 protein, mouse; D051157:Frizzled Receptors; C486339:Fzd3 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D012333:RNA, Messenger; D022661:RNA, Untranslated; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1
keywords: Isl1; axon guidance; internal capsule; mouse; prethalamus