title: Endoderm-specific deletion of Tbx1 reveals an FGF-independent role for Tbx1 in pharyngeal apparatus morphogenesis.
abstract: BACKGROUND
  The T-box transcription factor Tbx1, is essential for the normal development of multiple organ systems in the embryo. One of the most striking phenotypes in Tbx1-/- embryos is the failure of the caudal pharyngeal pouches to evaginate from the foregut endoderm. Despite considerable interest in the role of Tbx1 in development, the mechanisms whereby Tbx1 controls caudal pouch formation have remained elusive. In particular, the question as to how Tbx1 expression in the pharyngeal endoderm regulates pharyngeal pouch morphogenesis in the mouse embryo is not known.
  
  
  RESULTS
  To address this question, we produced mouse embryos in which Tbx1 was specifically deleted from the pharyngeal endoderm and, as expected, embryos failed to form caudal pharyngeal pouches. To determine the molecular mechanism, we examined expression of Fgf3 and Fgf8 ligands and downstream effectors. Although Fgf8 expression is greatly reduced in Tbx1-deficient endoderm, FGF signaling levels are unaffected. Furthermore, pouch morphogenesis is only partially perturbed by the loss of both Fgf3 and Fgf8 from the endoderm, indicating that neither are required for pouch formation.
  
  
  CONCLUSIONS
  Tbx1 deletion from the pharyngeal endoderm is sufficient to cause caudal pharyngeal arch segmentation defects by FGF-independent effectors that remain to be identified.
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College, London, United Kingdom.
authors.forename: Abigail
authors.initials: A
authors.lastname: Jackson
authors.forename: Sahrunizam
authors.initials: S
authors.lastname: Kasah
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Mansour
authors.forename: Bernice
authors.initials: B
authors.lastname: Morrow
authors.forename: M Albert
authors.initials: MA
authors.lastname: Basson
mesh_terms: D000818:Animals; D001934:Branchial Region / Q000196:embryology* / Q000378:metabolism; D004707:Endoderm / Q000196:embryology / Q000378:metabolism*; D051518:Fibroblast Growth Factor 3 / Q000235:genetics / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D010614:Pharynx / Q000196:embryology* / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C489197:Fgf3 protein, mouse; C496457:Fgf8 protein, mouse; D051518:Fibroblast Growth Factor 3; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D051524:Fibroblast Growth Factor 8
keywords: FGF; Tbx1; morphogenesis; pharyngeal endoderm