Regeneration of the distal airway epithelium after naphthalene injury. (A) Naphthalene (Npt) injury selectively kills all club cells in the distal conducting airways except for a few naphthalene-resistant club cells located near neuroendocrine (NE) bodies (NEBs) and at the bronchioalveolar duct junction (BADJ). Surviving ciliated cells spread out in an attempt to protect the denuded basement membrane and start to express Wnt7b, which then acts on airway smooth muscle cells to induce proliferation and Fgf10 secretion. Fgf10 acts back on surviving club stem cells to activate them and initiate regeneration. Thus, airway smooth muscle can be regarded as a club stem cell niche. Colored cell outlines represent lineage trace markers. (B) Lineage relationships of lung epithelial stem cells and their differentiated progeny during regeneration of the distal conducting airways after naphthalene injury. For details see main text. BASC, bronchioalveolar stem cell.