title: Tissue-specific roles for sonic hedgehog signaling in establishing thymus and parathyroid organ fate.
abstract: The thymus and parathyroids develop from third pharyngeal pouch (3rd pp) endoderm. Our previous studies show that Shh null mice have smaller, aparathyroid primordia in which thymus fate specification extends into the pharynx. SHH signaling is active in both dorsal pouch endoderm and neighboring neural crest (NC) mesenchyme. It is unclear which target tissue of SHH signaling is required for the patterning defects in Shh mutants. Here, we used a genetic approach to ectopically activate or delete the SHH signal transducer Smo in either pp endoderm or NC mesenchyme. Although no manipulation recapitulated the Shh null phenotype, manipulation of SHH signaling in either the endoderm or NC mesenchyme had direct and indirect effects on both cell types during fate specification and organogenesis. SHH pathway activation throughout pouch endoderm activated ectopic Tbx1 expression and partially suppressed the thymus-specific transcription factor Foxn1, identifying Tbx1 as a key target of SHH signaling in the 3rd pp. However, ectopic SHH signaling was insufficient to expand the GCM2-positive parathyroid domain, indicating that multiple inputs, some of which might be independent of SHH signaling, are required for parathyroid fate specification. These data support a model in which SHH signaling plays both positive and negative roles in patterning and organogenesis of the thymus and parathyroids.
authors.affiliation: Department of Genetics, Paul D. Coverdell Center, 500 DW Brooks Drive, University of Georgia, Athens, GA 30602, USA.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Bain
authors.affiliation: Department of Genetics, Paul D. Coverdell Center, 500 DW Brooks Drive, University of Georgia, Athens, GA 30602, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Gordon
authors.affiliation: Department of Genetics, Paul D. Coverdell Center, 500 DW Brooks Drive, University of Georgia, Athens, GA 30602, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: O'Neil
authors.affiliation: Department of Genetics, Paul D. Coverdell Center, 500 DW Brooks Drive, University of Georgia, Athens, GA 30602, USA.
authors.forename: Isaias
authors.initials: I
authors.lastname: Ramos
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas, M.D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957, USA.
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Richie
authors.affiliation: Department of Genetics, Paul D. Coverdell Center, 500 DW Brooks Drive, University of Georgia, Athens, GA 30602, USA nmanley@uga.edu.
authors.forename: Nancy R
authors.identifier: 0000-0001-8489-7764
authors.initials: NR
authors.lastname: Manley
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D038081:Organogenesis / Q000235:genetics*; D010280:Parathyroid Glands / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013950:Thymus Gland / Q000196:embryology* / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse
keywords: Endoderm; Morphogenesis; Mouse; Neural crest; Parathyroid; Smoothened; Sonic hedgehog; Thymus