Gardiner, J.R.* ; Jackson, A.L.* ; Gordon, J.* ; Lickert, H. ; Manley, N.R.* ; Basson, M.A.*
Localised inhibition of FGF signalling in the third pharyngeal pouch is required for normal thymus and parathyroid organogenesis.
Development 139, 3456-3466 (2012)
The thymus and parathyroid glands are derived from the third pharyngeal pouch endoderm. The mechanisms that establish distinct molecular domains in the third pouch and control the subsequent separation of these organ primordia from the pharynx are poorly understood. Here, we report that mouse embryos that lack two FGF feedback antagonists, Spry1 and Spry2, display parathyroid and thymus hypoplasia and a failure of these organ primordia to completely separate from the pharynx. We show that FGF ligands and downstream reporter genes are expressed in highly regionalised patterns in the third pouch and that sprouty gene deletion results in upregulated FGF signalling throughout the pouch endoderm. As a consequence, the initiation of markers of parathyroid and thymus fate is altered. In addition, a normal apoptotic programme that is associated with the separation of the primordia from the pharynx is disrupted, resulting in the maintenance of a thymus-pharynx attachment and a subsequent inability of the thymus to migrate to its appropriate position above the heart. We demonstrate that the sprouty genes function in the pharyngeal endoderm itself to control these processes and that the defects in sprouty-deficient mutants are, at least in part, due to hyper-responsiveness to Fgf8. Finally, we provide evidence to suggest that parathyroid hypoplasia in these mutants is due to early gene expression defects in the third pouch, whereas thymus hypoplasia is caused by reduced proliferation of thymic epithelial cells in the thymus primordium.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Fgf ; Sprouty ; Thymus ; Parathyroid ; Pharyngeal Pouch ; Endoderm ; Mouse; Sprouty Genes; Cell-Survival; Sonic-Hedgehog; Nude-Mice; Mouse; Expression; Morphogenesis; Endoderm; Cerebellum; BMP4
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2012
Prepublished im Jahr
HGF-Berichtsjahr
2012
ISSN (print) / ISBN
0950-1991
e-ISSN
1477-9129
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 139,
Heft: 18,
Seiten: 3456-3466
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Company of Biologists
Verlagsort
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
90000 - German Center for Diabetes Research
30201 - Metabolic Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er)
Helmholtz Diabetes Center
Stem Cell and Neuroscience
PSP-Element(e)
G-501900-231
G-502300-001
G-500890-001
Förderungen
Copyright
Erfassungsdatum
2012-09-27