Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an, 343009 Jiangxi, China.
Center for Drug Screening and Research, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000 Jiangxi, China.
Proc Natl Acad Sci U S A. 2021 Jan 12;118(2). doi: 10.1073/pnas.2009539118.
Planarian flatworms regenerate their heads and tails from anterior or posterior wounds and this regenerative blastema polarity is controlled by Wnt/β-catenin signaling. It is well known that a regeneration blastema of appendages of vertebrates such as fish and amphibians grows distally. However, it remains unclear whether a regeneration blastema in vertebrate appendages can grow proximally. Here, we show that a regeneration blastema in zebrafish fins can grow proximally along the proximodistal axis by calcineurin inhibition. We used fin excavation in adult zebrafish to observe unidirectional regeneration from the anterior cut edge (ACE) to the posterior cut edge (PCE) of the cavity and this unidirectional regeneration polarity occurs as the PCE fails to build blastemas. Furthermore, we found that calcineurin activities in the ACE were greater than in the PCE. Calcineurin inhibition induced PCE blastemas, and calcineurin hyperactivation suppressed fin regeneration. Collectively, these findings identify calcineurin as a molecular switch to specify the PCE blastema of the proximodistal axis and regeneration polarity in zebrafish fin.
涡虫的头部和尾部可以从前端或后端的伤口处再生,这种再生性的芽基极性由 Wnt/β-连环蛋白信号控制。众所周知,鱼类和两栖类等脊椎动物的附肢再生芽基会向远端生长。然而,脊椎动物附肢的再生芽基是否可以向近端生长仍不清楚。在这里,我们通过抑制钙调神经磷酸酶,证明了斑马鱼鳍的再生芽基可以沿着近-远轴的近端方向生长。我们通过在成年斑马鱼的鳍上进行挖掘来观察从腔的前端切口(ACE)到后端切口(PCE)的单向再生,这种单向再生极性的出现是由于 PCE 无法构建芽基。此外,我们发现 ACE 中的钙调神经磷酸酶活性大于 PCE。钙调神经磷酸酶抑制诱导 PCE 芽基形成,钙调神经磷酸酶过度激活抑制鳍再生。综上所述,这些发现表明钙调神经磷酸酶是一个分子开关,用于指定斑马鱼鳍近-远轴的 PCE 芽基和再生极性。