Hawkins M Brent, Zdral Sofía, Naranjo Silvia, Juliá Miguel, Sánchez-Martín Manuel, Daane Jacob M, Cumplido Nicolas, Jandzik David, Medeiros Daniel M, McMenamin Sarah K, Harris Matthew P, Tena Juan J, Ros Marian A
Boston Children's Hospital Department of Orthopedic Research, Boston, MA (USA).
Harvard Medical School Department of Genetics, Boston, MA (USA).
bioRxiv. 2025 Jul 5:2025.07.02.662459. doi: 10.1101/2025.07.02.662459.
Limb function requires polarized anatomy across the dorsal-ventral (DV) axis, but it is unclear when the capacity for DV differentiation of paired appendages arose in evolution. Here we define ancestral DV patterning programs in the fins of fishes. We show that the orthologue of the limb dorsal determinant, Lmx1b, is required to establish dorsality in zebrafish pectoral fins and is regulated by a conserved cis-regulatory hub. However, expression in median fins is unaffected by removal of the , suggesting its regulation is an evolutionary innovation specific to the paired appendages. Although we find the is highly conserved across gnathostomes, we identify specific alteration of this region in hillstream loaches, fishes which naturally parallel "double-ventral" fin phenotypes observed in and mutants. Altogether our findings indicate -mediated dorsal identity is an ancestral feature of paired appendages that provide a prepattern for limb evolution and lineage diversification.
肢体功能需要沿背腹（DV）轴的极化解剖结构，但尚不清楚成对附肢的DV分化能力在进化中何时出现。在这里，我们定义了鱼类鳍中的祖先DV模式程序。我们表明，肢体背侧决定因子Lmx1b的直系同源物是建立斑马鱼胸鳍背侧所必需的，并受一个保守的顺式调控枢纽调节。然而，去除该因子后，中鳍中的表达不受影响，这表明其调控是成对附肢特有的进化创新。尽管我们发现该因子在有颌类动物中高度保守，但我们在山溪鲃中发现了该区域的特定改变，山溪鲃自然呈现出在某些突变体中观察到的“双腹侧”鳍表型。总之，我们的研究结果表明，该因子介导的背侧身份是成对附肢的一个祖先特征，为肢体进化和谱系多样化提供了一个前模式。
