The pharyngeal apparatus is comprised of a series of pharyngeal arches that are defined by the evagination of endodermal pouches toward the ectoderm. Whilst the transcription factor T‐box 1 (Tbx1) and the Fibroblast growth factor 8 (Fgf8) are both required for caudal pouch formation, a role for these factors in the endoderm during pouch morphogenesis has not been confirmed. The observation that Fgf8 expression is lost in Tbx1 homozygous null mutant embryos has lead to the hypothesis that FGF8 functions directly downstream of TBX1 during pouch formation. To test this hypothesis the Sox17‐2A‐icre line was used to delete Fgf8, Fibroblast growth factor receptor 1 (Fgfr1) and Fibroblast growth factor receptor 2 (Fgfr2) and Tbx1 in the endoderm, and analyse the development of the pouches and their derivatives. In all embryos with an endoderm specific deletion of Tbx1, the caudal PA remained unsegmented as caudal pouches 3 and 4 do not form. The deletion of endodermal Tbx1 severely reduced the expression of Fgf8 in the endoderm; however, the expression of Fibroblast Growth Factor (FGF) signalling readouts was maintained. All rostral and caudal pouches are present in embryos with an endoderm specific deletion of Fgf8, indicating that the loss of Fgf8 alone from this epithelium is not sufficient to disrupt the process of pouch evagination. The compound deletion of Fgfr1 and Fgfr2 from the endoderm did not prevent pouch evagination but did cause 3rd pouch hypoplasia and the rostral pouches to fuse. These data indicate that FGF signalling downstream of Fgfr1 and Fgfr2 and Tbx1 are important for pouch formation but that they are likely to function in parallel pathways within the endoderm. Further data suggests that TBX1 may be acting in an FGF independent manner to control the polarity of actin within the endodermal epithelia. Overall this data reveals that both cell signalling and actin polarity must be tightly regulated within the endoderm for the pharyngeal pouches to form correctly.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:643576 |
| Date | January 2013 |
| Creators | Jackson, Abigail |
| Contributors | Basson, Albert; Sharpe, Paul |
| Publisher | King's College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://kclpure.kcl.ac.uk/portal/en/theses/the-regulation-of-pharyngeal-pouch-morphogenesis-by-tbx1-and-fgf-signalling-in-the-endoderm(fbd54a00-52cc-4fcc-ae8e-70662a660a4c).html |
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