The thymus and parathyroids develop from shared organ primordia derived from third pharyngeal pouch (3rd pp) endoderm. Our previous studies show that Sonic hedgehog (Shh) null mutants 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 mesenchyme, but it is unclear which target tissue of SHH signaling is required for the patterning defects seen in Shh mutants. We have taken a genetic approach to this question by ectopically activating or deleting the SHH signal transducer Smoothened (Smo) in either pharyngeal pouch endoderm or neural crest (NC) mesenchyme. While no individual manipulation recapitulated the Shh null mutant 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. Activation of the SHH pathway throughout the pouch endoderm activated ectopic Tbx1 expression and partially suppressed the thymus-specific transcription factor Foxn1, identifying Tbx1 as a critical target of SHH signaling in the 3rd pouch. However, ectopic SHH signaling was not sufficient to expand the GCM2 positive parathyroid domain, indicating that multiple inputs, some of which may 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.
Tissue-specific roles for Sonic hedgehog signaling in establishing thymus and parathyroid organ fate
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Virginia E. Bain, Julie Gordon, John D. O'Neil, Isaias Ramos, Ellen R. Richie, Nancy R. Manley; Tissue-specific roles for Sonic hedgehog signaling in establishing thymus and parathyroid organ fate. Development 2016; dev.141903. doi: https://doi.org/10.1242/dev.141903
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