title: Shh signalling restricts the expression of Gcm2 and controls the position of the developing parathyroids.
abstract: The parathyroid glands originate from the endoderm of the caudal pharyngeal pouches. How these parathyroids are restricted to developing in the caudal pouches is unclear. In this paper we investigate the role of Shh signalling in patterning the vertebrate pharyngeal pouches, and show that Hh signalling may be involved in restricting the expression of the parathyroid marker Gcm2 in the pharyngeal epithelium. In the chick and mouse, Shh signalling is excluded or highly reduced in the posterior/caudal pouches, where the parathyroid marker Gcm2 is expressed, while remaining at high levels in the more anterior pouches. Moreover, though the block of Shh signalling at early developmental stages results in the loss of chick Gcm2 expression, at later stages, it induces ectopic Gcm2 expression domains in the second and first pharyngeal epithelium, suggesting that HH signalling prevents Gcm2 in those tissues. These ectopic domains go on to express other parathyroid markers but do not migrate and develop into ectopic parathyroids. Differences in the expression of Gcm2 in the chick, mouse and zebrafish, correlate with changing patterns of Shh signalling, indicating a conserved regulatory mechanism that acts to define pouch derivatives.
authors.affiliation: King's College London, Department of Craniofacial Development and Orthodontics, Floor 27 Guy's Tower, Guy's Hospital, London Bridge, London SE1 9RT, UK.
authors.forename: Armelle
authors.initials: A
authors.lastname: Grevellec
authors.forename: Anthony
authors.initials: A
authors.lastname: Graham
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Tucker
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010280:Parathyroid Glands / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism; D000072079:Patched Receptors; D011247:Pregnancy; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014704:Veratrum Alkaloids / Q000494:pharmacology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D004268:DNA-Binding Proteins; C523486:Gcm2 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C080331:Hoxa3 protein, mouse; D009687:Nuclear Proteins; D010281:Parathyroid Hormone; D000072079:Patched Receptors; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; C465570:Shh protein, mouse; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D029961:Zebrafish Proteins; C501172:gcm2 protein, zebrafish; C000541:cyclopamine