斑马鱼肢体样骨骼结构形成的潜在发育潜能。
Latent developmental potential to form limb-like skeletal structures in zebrafish.
机构信息
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Orthopedic Research, Boston Children's Hospital, Boston, MA 02115, USA; Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Museum of Comparative Zoology, Harvard University, Cambridge, MA 02138, USA.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Orthopedic Research, Boston Children's Hospital, Boston, MA 02115, USA.
出版信息
Cell. 2021 Feb 18;184(4):899-911.e13. doi: 10.1016/j.cell.2021.01.003. Epub 2021 Feb 4.
Changes in appendage structure underlie key transitions in vertebrate evolution. Addition of skeletal elements along the proximal-distal axis facilitated critical transformations, including the fin-to-limb transition that permitted generation of diverse modes of locomotion. Here, we identify zebrafish mutants that form supernumerary long bones in their pectoral fins. These new bones integrate into musculature, form joints, and articulate with neighboring elements. This phenotype is caused by activating mutations in previously unrecognized regulators of appendage patterning, vav2 and waslb, that function in a common pathway. This pathway is required for appendage development across vertebrates, and loss of Wasl in mice causes defects similar to those seen in murine Hox mutants. Concordantly, formation of supernumerary bones requires Hox11 function, and mutations in the vav2/wasl pathway drive enhanced expression of hoxa11b, indicating developmental homology with the forearm. Our findings reveal a latent, limb-like pattern ability in fins that is activated by simple genetic perturbation.
附肢结构的变化是脊椎动物进化的关键。沿着近-远轴添加骨骼元素促进了关键的转变,包括鳍到肢的转变,这使得多样化的运动模式得以产生。在这里,我们鉴定了在胸鳍中形成额外长骨的斑马鱼突变体。这些新的骨骼与肌肉整合,形成关节,并与相邻的元素相连。这种表型是由以前未被识别的附肢模式形成的调节因子 vav2 和 waslb 的激活突变引起的,它们在一个共同的途径中起作用。该途径在整个脊椎动物的附肢发育中是必需的,并且在小鼠中缺失 Wasl 会导致与在鼠类 Hox 突变体中观察到的相似的缺陷。一致地,额外骨骼的形成需要 Hox11 功能,并且 vav2/wasl 途径的突变驱动 hoxa11b 的表达增强,表明与前臂的发育同源性。我们的研究结果揭示了一种潜在的、类似肢体的模式能力,这种能力在鳍中被简单的遗传扰动激活。