| First Author | Atsuta Y | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 43 | Pages | 21592-21601 |
| PubMed ID | 31591237 | Mgi Jnum | J:280678 |
| Mgi Id | MGI:6368987 | Doi | 10.1073/pnas.1908981116 |
| Citation | Atsuta Y, et al. (2019) L-type voltage-gated Ca(2+) channel CaV1.2 regulates chondrogenesis during limb development. Proc Natl Acad Sci U S A 116(43):21592-21601 |
| abstractText | All cells, including nonexcitable cells, maintain a discrete transmembrane potential (V mem), and have the capacity to modulate V mem and respond to their own and neighbors' changes in V mem Spatiotemporal variations have been described in developing embryonic tissues and in some cases have been implicated in influencing developmental processes. Yet, how such changes in V mem are converted into intracellular inputs that in turn regulate developmental gene expression and coordinate patterned tissue formation, has remained elusive. Here we document that the V mem of limb mesenchyme switches from a hyperpolarized to depolarized state during early chondrocyte differentiation. This change in V mem increases intracellular Ca(2+) signaling through Ca(2+) influx, via CaV1.2, 1 of L-type voltage-gated Ca(2+) channels (VGCCs). We find that CaV1.2 activity is essential for chondrogenesis in the developing limbs. Pharmacological inhibition by an L-type VGCC specific blocker, or limb-specific deletion of CaV1.2, down-regulates expression of genes essential for chondrocyte differentiation, including Sox9, Col2a1, and Agc1, and thus disturbs proper cartilage formation. The Ca(2+)-dependent transcription factor NFATc1, which is a known major transducer of intracellular Ca(2+) signaling, partly rescues Sox9 expression. These data reveal instructive roles of CaV1.2 in limb development, and more generally expand our understanding of how modulation of membrane potential is used as a mechanism of developmental regulation. |
