在指趾进化过程中，祖先泄殖腔调控景观的共同选择，这一成果由瑞士日内瓦大学Denis Duboule团队经过不懈努力而取得。相关论文发表在2025年9月17日出版的《自然》杂志上。

课题组研究人员通过比较评估它们完全缺失的影响，从遗传学上评估了斑马鱼Hoxd调控景观的功能。研究小组发现，与小鼠不同，在鱼类中，这些区域的缺失不会破坏远端鳍发育过程中Hoxd基因的转录。相比之下，该课题组人员发现这种缺陷导致泄殖腔内表达缺失，这是一种与哺乳动物泌尿生殖系统有关的结构，并且远端hox13基因对于正确的泄殖腔形成至关重要。由于Hoxd基因在泌尿生殖系统中的调控依赖于位于控制手指发育的同一染色质结构域的增强子，因此该研究团队提出，目前在远端肢体中活跃的调控环境是在四足动物中从一个预先存在的局部调控机制中作为一个整体被吸收的。

据了解，脊椎动物进化过程中从鳍到肢的转变一直是研究进化变化背后的发展机制的核心。在这种背景下，通过对Hox基因调控的功能分析来推断进化轨迹对于解释新特征的起源至关重要。在四足动物中，Hoxd基因在发育趾中的转录依赖于一组形成大调控格局的增强子。斑马鱼缺少趾，但却有一个相同的对应体，这表明它们具有深层同源性，或者在远端鳍和四肢下有共同的发育基础。然而，这个监管程序是如何演变的仍未得到解决。

附：英文原文

Title: Co-option of an ancestral cloacal regulatory landscape during digit evolution

Author: Hintermann, Aurlie, Bolt, Christopher C., Hawkins, M. Brent, Valentin, Guillaume, Lopez-Delisle, Lucille, Ryan, Madeline M., Gitto, Sandra, Barrera Gmez, Paula, Mascrez, Bndicte, Mansour, Thomas A., Nakamura, Tetsuya, Harris, Matthew P., Shubin, Neil H., Duboule, Denis

Issue&Volume: 2025-09-17

Abstract: The fin-to-limb transition in vertebrate evolution has been central to the study of how development underlies evolutionary change. In this context, the functional analysis of Hox gene regulation to infer evolutionary trajectories has been critical to explain the origin of new features. In tetrapods, the transcription of Hoxd genes in developing digits depends on a set of enhancers forming a large regulatory landscape1,2. The presence of a syntenic counterpart in zebrafish, which lacks digits, suggests deep homology3 or shared developmental foundations underlying distal fin and limbs. However, how this regulatory program evolved has remained unresolved. We genetically evaluated the function of the zebrafish Hoxd regulatory landscapes by comparatively assessing the effects of their full deletions. We show that, unlike in mice, deletion of these regions in fish does not disrupt hoxd gene transcription during distal fin development. By contrast, we found that this deficiency leads to the loss of expression within the cloaca, a structure related by ancestry to the mammalian urogenital sinus, and that distal hox13 genes are essential for correct cloacal formation. Because Hoxd gene regulation in the mouse urogenital sinus relies on enhancers located in this same chromatin domain that controls digit development, we propose that the current regulatory landscape active in distal limbs was co-opted as a whole in tetrapods from a pre-existing cloacal regulatory machinery.

DOI: 10.1038/s41586-025-09548-0

Source: https://www.nature.com/articles/s41586-025-09548-0