Independent size regulation of bones and appendages in zebrafish

Abstract

During development, organ size and the size of its components must be coordinated. However, the mechanisms integrating these two growth processes remain poorly understood. Here, using the zebrafish fin as a model, we investigated how bioelectric signaling regulates overall appendage size and fin-ray bone segment length. To manipulate bioelectric signaling, we expressed the hyperactive potassium channel mutant kcnk5bW169L or the dominant-negative connexin mutant Cx43T154A under a common set of cell-type-specific promoters. Cell-type-specific bioelectric manipulation in keratinocytes primarily affected fin size, whereas manipulation in osteoblasts preferentially altered fin-ray segment length. Combining these manipulations generated enlarged fins with short segments or small fins with long segments, providing direct evidence that fin size and fin-ray segment length can be regulated independently. Furthermore, optogenetic manipulation demonstrated that membrane potential itself can regulate fin size and fin-ray segment length. Together, these findings reveal that bioelectric signaling can independently regulate appendage growth and skeletal element growth through distinct cellular targets.