Connexin43 (GJA1) is required in the population of dividing cells during fin regeneration
Connexin43 (GJA1) is required in the population of dividing cells during fin regeneration
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DOI：
10.1016/j.ydbio.2008.02.051
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发表时间：
2008-05-15
影响因子：
2.7
通讯作者：
Iovine, M. Kathryn
中科院分区：
文献类型：
--
作者：
Hoptak-Solga, Angela D.;Nielsen, Sarah;Iovine, M. Kathryn
在斑马鱼中，间隙连接基因connexin43的突变导致短骨鳍片段，从而产生短鳍表型。Sof（b123）突变体的鳍长度是野生型鳍的一半，并且cx43 mRNA的水平降低。我们发现软（b123）再生鳍表现出细胞增殖水平降低。有趣的是，在野生型和突变型鳍之间，每单位长度鳍生长的分裂细胞数量是相似的，这表明进入细胞周期的细胞数量在软鳍中受到特异性影响（b123）。在有丝分裂细胞中发现了cx43的表达，这进一步表明cx43可能有助于建立或维持分裂细胞的群体。事实上，表现出高或低水平间隙连接通讯的错义等位基因揭示了直接细胞-细胞通讯缺陷、细胞增殖和片段长度之间的相关性。最后，在成体再生鳍中，cx43基因的靶向敲低再现了Sof（b123）表型，表明cx43的缺失足以降低细胞增殖和片段长度。我们假设分裂细胞间的间隙连接通讯水平调节细胞增殖水平并最终调节骨生长。(C) 2008爱思唯尔公司版权所有。
In zebrafish, mutations in the gap junction gene connexin43 lead to short bony fin ray segments that give rise to the short fin phenotype. The Sof(b123) mutant exhibits fins that are half the length of wild-type fins and have reduced levels of cx43 mRNA. We find that sof(b123) regenerating fins exhibit reduced levels of cell proliferation. Interestingly, the number of dividing cells per unit length of fin growth is similar between wild-type and mutant fins, suggesting that the number of cells that enter the cell cycle is specifically affected in sof(b123). Expression of cx43 is identified in mitotic cells, which further suggests that Cx43 may contribute to establishing or maintaining the population of dividing cells. Indeed, missense alleles exhibiting high OF low levels of gap junctional communication reveal a correlation between defects in direct cell-cell communication, cell proliferation, and segment length. Finally, targeted gene knockdown of cx43 in adult regenerating fins recapitulates the Sof(b123) phenotype, revealing that the loss of Cx43 is sufficient to reduce both cell proliferation and segment length. We hypothesize that the level of gap junctional intercellular communication among dividing cells regulates the level of cell proliferation and ultimately regulates bone growth. (C) 2008 Elsevier Inc. All rights reserved.