title: β-catenin is required in the neural crest and mesencephalon for pituitary gland organogenesis.
abstract: The pituitary gland is a highly vascularized tissue that requires coordinated interactions between the neural ectoderm, oral ectoderm, and head mesenchyme during development for proper physiological function. The interactions between the neural ectoderm and oral ectoderm, especially the role of the pituitary organizer in shaping the pituitary precursor, Rathke's pouch, are well described. However, less is known about the role of head mesenchyme in pituitary organogenesis. The head mesenchyme is derived from definitive mesoderm and neural crest, but the relative contributions of these tissues to the mesenchyme adjacent to the pituitary are not known.
  
  
  
  We carried out lineage tracing experiments using two neural crest-specific mouse cre lines, Wnt1-cre and P0-cre, and determined that the head mesenchyme rostral to the pituitary gland is neural crest derived. To assess the role of the neural crest in pituitary development we ablated it, using Wnt1-cre to delete Ctnnb1 (β-catenin), which is required for neural crest development. The Wnt1-cre is active in the neural ectoderm, principally in the mesencephalon, but also in the posterior diencephalon. Loss of β-catenin in this domain causes a rostral shift in the ventral diencephalon, including the pituitary organizer, resulting in pituitary dysmorphology. The neural crest deficient embryos have abnormally dilated pituitary vasculature due to a loss of neural crest derived pericytes.
  
  
  
  β-catenin in the Wnt1 expression domain, including the neural crest, plays a critical role in regulation of pituitary gland growth, development, and vascularization.
authors.affiliation: Department of Biological Sciences, University of South Carolina, 715 Sumter St. CLS room 401, Columbia, SC, 29208, USA. swdavis@mailbox.sc.edu.
authors.forename: Shannon W
authors.initials: SW
authors.lastname: Davis
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Mortensen
authors.affiliation: Department of Biological Sciences, University of South Carolina, 715 Sumter St. CLS room 401, Columbia, SC, 29208, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Keisler
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA.|Present address: Department of Genetics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Zacharias
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Gage
authors.affiliation: Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, 860-0811, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yamamura
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Camper
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D018993:Myelin P0 Protein / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics*; D010902:Pituitary Gland / Q000196:embryology / Q000378:metabolism*; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D018993:Myelin P0 Protein; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051176:beta Catenin
keywords: Neural crest; Organogenesis; Pituitary gland; Vasculature; β-catenin