title: The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling.
abstract: BACKGROUND
  The pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon, and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke's pouch, with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between the pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke's pouch. Little is currently known about the formation and function of this structure. Here we have investigated molecular mechanisms driving the formation of the buccohypophyseal canal and their evolutionary significance.
  
  
  RESULTS
  We show that Rathke's pouch is located at a boundary region delineated by endoderm, neural crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1, R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron X-ray microtomography after iodine staining in mouse embryos, the pouch has a lobulated three-dimensional structure that embraces the descending diencephalon during pituitary formation. Polaris(fl/fl); Wnt1-Cre, Ofd1(-/-) and Kif3a(-/-) primary cilia mouse mutants have abnormal sonic hedgehog (Shh) signaling and all present with malformations of the anterior pituitary gland and midline structures of the anterior cranial base. Changes in the expressions of Shh downstream genes are confirmed in Gas1(-/-) mice. From an evolutionary perspective, persistence of the buccohypophyseal canal is a basal character for all vertebrates and its maintenance in several groups is related to a specific morphology of the midline that can be related to modulation in Shh signaling.
  
  
  CONCLUSIONS
  These results provide insight into a poorly understood ancestral vertebrate structure. It appears that the opening of the buccohypophyseal canal depends upon Shh signaling and that modulation in this pathway most probably accounts for its persistence in phylogeny.
authors.affiliation: Department of Craniofacial Development and Stem Cell Research, Comprehensive Biomedical Research Center, Dental Institute, King's College London, London, UK. roman.khonsari@kcl.ac.uk
authors.forename: Roman H
authors.initials: RH
authors.lastname: Khonsari
authors.forename: Maisa
authors.initials: M
authors.lastname: Seppala
authors.forename: Alan
authors.initials: A
authors.lastname: Pradel
authors.forename: Hugo
authors.initials: H
authors.lastname: Dutel
authors.forename: Gaël
authors.initials: G
authors.lastname: Clément
authors.forename: Oleg
authors.initials: O
authors.lastname: Lebedev
authors.forename: Sarah
authors.initials: S
authors.lastname: Ghafoor
authors.forename: Michaela
authors.initials: M
authors.lastname: Rothova
authors.forename: Abigael
authors.initials: A
authors.lastname: Tucker
authors.forename: John G
authors.initials: JG
authors.lastname: Maisey
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Fan
authors.forename: Maiko
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohazama
authors.forename: Paul
authors.initials: P
authors.lastname: Tafforeau
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
authors.forename: Jill
authors.initials: J
authors.lastname: Helms
authors.forename: Courtney J
authors.initials: CJ
authors.lastname: Haycraft
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Philippe
authors.initials: P
authors.lastname: Janvier
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Cobourne
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000378:metabolism; D002923:Cilia / Q000378:metabolism; D004475:Ectoderm / Q000196:embryology / Q000378:metabolism; D053476:Extinction, Biological; D005399:Fishes / Q000196:embryology; D005580:Fossils; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007568:Jaw / Q000196:embryology; D051379:Mice; D009055:Mouth / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*; D015398:Signal Transduction; D012886:Skull / Q000033:anatomy & histology / Q000196:embryology; D014714:Vertebrates / Q000196:embryology*
chemical_list: D018797:Cell Cycle Proteins; D058851:GPI-Linked Proteins; C501180:Gas1 protein, mouse; D053823:Hedgehog Proteins
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