ABSTRACT
Basal progenitor cells are crucial for the establishment and maintenance of the tracheal epithelium. However, it remains unclear how these progenitor cells are specified during foregut development. Here, we found that ablation of the Wnt chaperone protein Gpr177 (also known as Wntless) in mouse tracheal epithelium causes a significant reduction in the number of basal progenitor cells accompanied by cartilage loss in Shh-Cre;Gpr177loxp/loxp mutants. Consistent with the association between cartilage and basal cell development, Nkx2.1+p63+ basal cells are co-present with cartilage nodules in Shh-Cre;Ctnnb1DM/loxp mutants, which maintain partial cell-cell adhesion but not the transcription regulation function of β-catenin. More importantly, deletion of Ctnnb1 in the mesenchyme leads to the loss of basal cells and cartilage, concomitant with reduced transcript levels of Fgf10 in Dermo1-Cre;Ctnnb1loxp/loxp mutants. Furthermore, deletion of Fgf receptor 2 (Fgfr2) in the epithelium also leads to significantly reduced numbers of basal cells, supporting the importance of Wnt/Fgf crosstalk in early tracheal development.
Footnotes
Author contributions
Conceptualization: J.Q., M.J.; Methodology: Z.H., Y.Z., M.J.; Validation: Q.W., X.S., Y.L., M.J.; Formal analysis: J.Q., M.J.; Investigation: Z.H., Q.W., X.S., H.C., Y.Z., Y.Y., J.Q., M.J.; Resources: Y.L., Y.Z., M.M., Y.Y., J.Q.; Data curation: Z.H., M.J.; Writing - original draft: J.Q., M.J.; Writing - review & editing: J.Q., M.J.; Visualization: H.C.; Supervision: J.Q., M.J.; Project administration: J.Q.; Funding acquisition: J.Q.
Funding
This work is partly supported by the National Heart, Lung, and Blood Institute (R01HL132996 to J.Q.) and the Price Family Foundation. Deposited in PMC for release after 12 months.
