Gjd4, encoding the Cx46.8 protein, is a connexin gene conserved across vertebrate lineages. Gap junction (GJ) channels formed by connexins mediate bioelectric signaling, and Gjd4-related GJ channels are crucial for slow muscle development and function. They transmit spinal-cord-generated neural activity to developing slow muscle cells and synchronize the activity spread, which is essential for appropriate myofiber organization in the developing neuromuscular system [1,2].

In a study on Cx39-deficient mice (where the coding region of the Gjd4 gene was replaced by eGFP), myogenesis in embryos was accelerated, as indicated by increased myogenin expression and increased Cx43 expression in developing skeletal muscle. Also, the regeneration process of skeletal muscle in these mice was accelerated, with earlier onset of MyoD and myogenin expression. It was hypothesized that Cx43 may compensate for the loss of Cx39 during myogenesis and regeneration [3].

In conclusion, Gjd4 is essential for slow muscle development, function, and myofiber organization through mediating bioelectric signaling. The gene knockout model in mice has revealed its role in myogenesis and skeletal muscle regeneration, contributing to our understanding of developmental myopathies and muscle-related biological processes.

References:

1. Lukowicz-Bedford, Rachel M, Eisen, Judith S, Miller, Adam C. 2024. Gap-junction-mediated bioelectric signaling required for slow muscle development and function in zebrafish. In Current biology : CB, 34, 3116-3132.e5. doi:10.1016/j.cub.2024.06.007. https://pubmed.ncbi.nlm.nih.gov/38936363/

2. Lukowicz-Bedford, R M, Eisen, J S, Miller, A C. 2023. Gap junction mediated bioelectric coordination is required for slow muscle development, organization, and function. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.12.20.572619. https://pubmed.ncbi.nlm.nih.gov/38187655/

3. von Maltzahn, Julia, Wulf, Volker, Matern, Gabi, Willecke, Klaus. 2011. Connexin39 deficient mice display accelerated myogenesis and regeneration of skeletal muscle. In Experimental cell research, 317, 1169-78. doi:10.1016/j.yexcr.2011.01.017. https://pubmed.ncbi.nlm.nih.gov/21272575/