Abnormal tracheal cartilage formation in mice lacking Cav3.2 T‐type Ca 2+ channels (540.3)

Ca 2+ influx is crucial in initiating the differentiation of mesenchymal cells into chondrocytes, but which Ca 2+ channels are involved remains uncertain. Here we show that the T‐type voltage‐gated Ca 2+ channel Ca v 3.2 is essential for tracheal chondrogenesis. Mice lacking this channel (Ca v 3.2 ‐/‐ ) showed congenital tracheal stenosis because of incomplete formation of cartilaginous tracheal support. Conversely, Ca v 3.2 overexpression in ATDC5 cells enhanced chondrogenesis, which could be blunted by both blocking T‐type Ca 2+ channels and inhibiting calcineurin and suggests that Ca v 3.2 is responsible for Ca 2+ influx during chondrogenesis. Finally, the expression of sex‐determination region of Y chromosome (SRY)‐related high mobility group‐Box gene 9 (Sox9) was reduced in Ca v 3.2 ‐/‐ tracheas. Ca v 3.2‐dependent Sox9 upregulation required a putative nuclear factor of activated T cell (NFAT) binding site identified within the mouse Sox9 promoter. The signaling pathway underlying Ca 2+ ‐induced chondrogenesis involves the Ca v 3.2 T‐type channel and depends on calcineurin and NFAT.