title: Hes1 is required for the development of pharyngeal organs and survival of neural crest-derived mesenchymal cells in pharyngeal arches.
abstract: Hes genes are required to maintain diverse progenitor cell populations during embryonic development. Loss of Hes1 results in a spectrum of malformations of pharyngeal endoderm-derived organs, including the ultimobranchial body (progenitor of C cells), parathyroid, thymus and thyroid glands, together with highly penetrant C-cell aplasia (81%) and parathyroid aplasia (28%). The hypoplastic parathyroid and thymus are mostly located around the pharyngeal cavity, even at embryonic day (E) 15.5 to E18.5, indicating the failure of migration of the organs. To clarify the relationship between these phenotypes and neural crest cells, we examine fate mapping of neural crest cells colonized in pharyngeal arches in Hes1 null mutants by using the Wnt1-Cre/R26R reporter system. In null mutants, the number of neural crest cells labeled by X-gal staining is markedly decreased in the pharyngeal mesenchyme at E12.5 when the primordia of the thymus, parathyroid and ultimobranchial body migrate toward their destinations. Furthermore, phospho-Histone-H3-positive proliferating cells are reduced in number in the pharyngeal mesenchyme at this stage. Our data indicate that the development of pharyngeal organs and survival of neural-crest-derived mesenchyme in pharyngeal arches are critically dependent on Hes1. We propose that the defective survival of neural-crest-derived mesenchymal cells in pharyngeal arches directly or indirectly leads to deficiencies of pharyngeal organs.
authors.affiliation: Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan. kameda@med.kitasato-u.ac.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kameda
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Saitoh
authors.forename: Noriko
authors.initials: N
authors.lastname: Nemoto
authors.forename: Tokio
authors.initials: T
authors.lastname: Katoh
authors.forename: Sachiko
authors.initials: S
authors.lastname: Iseki
authors.forename: Takao
authors.initials: T
authors.lastname: Fujimura
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001934:Branchial Region / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000196:embryology*; D038081:Organogenesis / Q000235:genetics / Q000502:physiology; D010280:Parathyroid Glands / Q000166:cytology / Q000196:embryology; D010614:Pharynx / Q000166:cytology / Q000196:embryology* / Q000294:innervation; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology; D000072056:Transcription Factor HES-1; D014460:Ultimobranchial Body / Q000166:cytology / Q000196:embryology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse