title: Overlapping roles and collective requirement for the coreceptors GAS1, CDO, and BOC in SHH pathway function.
abstract: Secreted Hedgehog (HH) ligands signal through the canonical receptor Patched (PTCH1). However, recent studies implicate three additional HH-binding, cell-surface proteins, GAS1, CDO, and BOC, as putative coreceptors for HH ligands. A central question is to what degree these coreceptors function similarly and what their collective requirement in HH signal transduction is. Here we provide evidence that GAS1, CDO, and BOC play overlapping and essential roles during HH-mediated ventral neural patterning of the mammalian neural tube. Specifically, we demonstrate two important roles for these molecules: an early role in cell fate specification of multiple neural progenitors and a later role in motor neuron progenitor maintenance. Most strikingly, genetic loss-of-function experiments indicate an obligatory requirement for GAS1, CDO, and BOC in HH pathway activity in multiple tissues.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, 48109, USA. benallen@umich.edu
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Allen
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Song
authors.forename: Luisa
authors.initials: L
authors.lastname: Izzi
authors.forename: Irene W
authors.initials: IW
authors.lastname: Althaus
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charron
authors.forename: Robert S
authors.initials: RS
authors.lastname: Krauss
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
mesh_terms: D000818:Animals; D019521:Body Patterning; D015815:Cell Adhesion Molecules / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005121:Extremities / Q000196:embryology; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins / Q000502:physiology; D053823:Hedgehog Proteins / Q000502:physiology*; D007074:Immunoglobulin G / Q000502:physiology*; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D000075746:Zinc Finger Protein Gli2
chemical_list: C510745:Boc protein, mouse; C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D058851:GPI-Linked Proteins; C501180:Gas1 protein, mouse; C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D007074:Immunoglobulin G; D051741:Kruppel-Like Transcription Factors; D011956:Receptors, Cell Surface; C465570:Shh protein, mouse; D000075746:Zinc Finger Protein Gli2