Östlund-Sholars Gabrielle, Lemaire Laurence A, Levine Michael S
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Department of Biology, Saint Louis University, St. Louis, MO 63108, USA.
bioRxiv. 2025 Jun 25:2025.06.18.660479. doi: 10.1101/2025.06.18.660479.
Neural tube closure (NTC) is a conserved morphogenetic process in chordates, during which the neural plate folds and fuses to form a closed neural tube. While the mechanical forces and signaling pathways governing NTC have been characterized in vertebrates, the transcriptional programs coordinating cell behaviors during closure remain less understood. Here, we identify a transcriptional circuit involving , , and that regulates dorsal midline dynamics during NTC in the tunicate . High-resolution HCR hybridization reveals that is dynamically enriched at the zippering point and advances in a posterior-to-anterior transcription wave, while is downregulated in the same region, marking a transition from early neural patterning to morphogenetic execution. As closure progresses, and exhibit complementary, alternating expression at the dorsal midline, resembling a pair-rule-like pattern. Misexpression studies show that promotes proliferation and activates its own expression, whereas limits proliferation and impedes closure. Single-cell RNA-seq reveals transcriptionally distinct dorsal neural populations enriched for or , supporting spatially organized cell-cycle states. These findings suggest that a transcriptional switch from to , followed by spatially alternating and activity, coordinates proliferation and neural fold fusion during NTC. This mechanism may represent a general strategy for regulating epithelial remodeling in animal embryos.
神经管闭合（NTC）是脊索动物中一个保守的形态发生过程，在此过程中神经板折叠并融合形成一个封闭的神经管。虽然在脊椎动物中已经对控制NTC的机械力和信号通路进行了表征，但在闭合过程中协调细胞行为的转录程序仍不太清楚。在这里，我们在被囊动物中鉴定出一个涉及[具体基因1]、[具体基因2]和[具体基因3]的转录回路，该回路在NTC期间调节背中线动态。高分辨率HCR杂交显示[具体基因1]在拉链点动态富集，并以从后到前的转录波形式推进，而[具体基因2]在同一区域下调，标志着从早期神经模式形成到形态发生执行的转变。随着闭合的进行，[具体基因2]和[具体基因3]在背中线表现出互补的交替表达，类似于成对规则样模式。错误表达研究表明[具体基因1]促进增殖并激活其自身表达，而[具体基因2]限制增殖并阻碍闭合。单细胞RNA测序揭示了富含[具体基因1]或[具体基因2]的转录上不同的背侧神经群体，支持空间组织的细胞周期状态。这些发现表明，从[具体基因1]到[具体基因2]的转录开关，随后是[具体基因2]和[具体基因3]的空间交替活性，在NTC期间协调增殖和神经褶融合。这种机制可能代表了调节动物胚胎上皮重塑的一般策略。
