CNRS, Sorbonne Université, UMR7232-Biologie Intégrative des Organismes Marins, Observatoire Océanologique, Banyuls-sur-Mer, France.
Centre de Ressources Biologiques Marines, Sorbonne Université, Observatoire Océanologique, UMS 2348, Banyuls-sur-Mer, France.
Nat Commun. 2024 Nov 25;15(1):10194. doi: 10.1038/s41467-024-54042-2.
The mode of evolution of left-right asymmetries in the vertebrate habenulae remains largely unknown. Using a transcriptomic approach, we show that in a cartilaginous fish, the catshark Scyliorhinus canicula, habenulae exhibit marked asymmetries, in both their medial and lateral components. Comparisons across vertebrates suggest that those identified in lateral habenulae reflect an ancestral gnathostome trait, partially conserved in lampreys, and independently lost in tetrapods and neopterygians. Asymmetry formation involves distinct mechanisms in the catshark lateral and medial habenulae. Medial habenulae are submitted to a marked, asymmetric temporal regulation of neurogenesis, undetectable in their lateral counterparts. Conversely, asymmetry formation in lateral habenulae results from asymmetric choices of neuronal identity in post-mitotic progenitors, a regulation dependent on the repression of Wnt signaling by Nodal on the left. Based on comparisons with the mouse and the zebrafish, we propose that habenular asymmetry formation involves a recurrent developmental logic across vertebrates, which relies on conserved, temporally regulated genetic programs sequentially shaping choices of neuronal identity on both sides and asymmetrically modified by Wnt activity.
左右不对称在脊椎动物缰核中的进化模式在很大程度上仍是未知的。通过转录组学的方法，我们发现软骨鱼（猫鲨）的缰核存在明显的左右不对称，包括其内侧和外侧部分。在比较不同的脊椎动物后，我们发现鉴定出的外侧缰核反映了一个古老的有颌类特征，在七鳃鳗中部分保守，而在四足动物和新鳍鱼中则独立丢失。不对称的形成涉及软骨鱼外侧和内侧缰核中不同的机制。内侧缰核受到明显的、不对称的神经发生时间调控，而在其外侧对应物中则无法检测到。相反，外侧缰核中的不对称形成源于有丝分裂后祖细胞中神经元身份的不对称选择，这种调控依赖于 Nodal 对左侧 Wnt 信号的抑制。通过与小鼠和斑马鱼的比较，我们提出缰核的不对称形成涉及一个在脊椎动物中反复出现的发育逻辑，它依赖于保守的、受时间调控的遗传程序，这些程序在两侧依次塑造神经元身份的选择，并受到 Wnt 活性的不对称修饰。
