FGFR2b regulation of Wnt signaling controls parasympathetic innervation during submandibular gland development.

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NIDCR	DEV-9

Authors

• W.M. Knosp
• S.M. Knox
• G.R. Martin
• M.P. Hoffman

Abstract

Submandibular gland (SMG) organogenesis involves the coordinated development of the epithelium and parasympathetic ganglia (PSG), which condense and associate with the primary duct. FGFR2b signaling is required for both epithelial and PSG development as these structures are absent in Fgf10-/- embryos. Signals from the PSG maintain the Krt5+ progenitor cells in the epithelium but it is not known whether the epithelium plays an inductive role in PSG development. We hypothesized that secreted factor(s) from the duct promote PSG condensation and association with the epithelium. We performed microarray analysis of early SMG end buds and ducts, identifying increased Wnt gene expression in the duct. WNT-reporter mice show that WNT signaling occurs in PSG neurons early in development. WNTs promote PSG proliferation and WNT inhibitors disrupt the epithelial-PSG association. Treatment with FGF reduces both WNT signaling and PSG condensation/association with the duct, and reduces Krt5+ progenitor cells. Increasing endogenous FGFR2b signaling by deleting the signaling antagonists Sprouty1 and Sprouty2 results in a similar but more severe phenotype. In conclusion, we have identified a novel role for WNT signaling in promoting PSG proliferation and association with the duct during SMG development, which establishes neuronal-epithelial communication required for progenitor cell maintenance and SMG development.

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