Department of Biology, Wheaton College, Norton, MA, 02766, USA.
Department of Genetics, Harvard Medical School, Boston, MA, 02124, USA; Department of Orthopaedic Research, Boston Children's Hospital, Boston, MA, 02124, USA.
Dev Biol. 2019 Dec 15;456(2):164-178. doi: 10.1016/j.ydbio.2019.08.016. Epub 2019 Aug 28.
The coordination of growth during development establishes proportionality within and among the different anatomic structures of organisms. Innate memory of this proportionality is preserved, as shown in the ability of regenerating structures to return to their original size. Although the regulation of this coordination is incompletely understood, mutant analyses of zebrafish with long-finned phenotypes have uncovered important roles for bioelectric signaling in modulating growth and size of the fins and barbs. To date, long-finned mutants identified are caused by hypermorphic mutations, leaving unresolved whether such signaling is required for normal development. We isolated a new zebrafish mutant, schleier, with proportional overgrowth phenotypes caused by a missense mutation and loss of function in the K-Cl cotransporter Kcc4a. Creation of dominant negative Kcc4a in wild-type fish leads to loss of growth restriction in fins and barbs, supporting a requirement for Kcc4a in regulation of proportion. Epistasis experiments suggest that Kcc4a and the two-pore potassium channel Kcnk5b both contribute to a common bioelectrical signaling response in the fin. These data suggest that an integrated bioelectric signaling pathway is required for the coordination of size and proportion during development.
在发育过程中，生长的协调在生物体的不同解剖结构内部和之间建立了比例性。这种比例性的先天记忆被保留下来，正如再生结构能够恢复到原始大小的能力所表明的那样。尽管这种协调的调节机制还不完全清楚，但对具有长鳍表型的斑马鱼的突变体分析揭示了生物电信号在调节鳍和刺的生长和大小方面的重要作用。迄今为止，已鉴定的长鳍突变体是由超形突变引起的，尚不清楚这种信号是否是正常发育所必需的。我们分离了一种新的斑马鱼突变体 schleier，它由于错义突变和 K-Cl 共转运蛋白 Kcc4a 的功能丧失而导致比例过度生长表型。在野生型鱼中创建显性负性 Kcc4a 会导致鳍和刺的生长受限丧失，支持 Kcc4a 在调节比例中的作用。上位性实验表明，Kcc4a 和双孔钾通道 Kcnk5b 都有助于鳍中的共同生物电信号反应。这些数据表明，在发育过程中，大小和比例的协调需要一个整合的生物电信号通路。
