Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, Haifa, Israel.
Dev Dyn. 2022 Aug;251(8):1322-1339. doi: 10.1002/dvdy.474. Epub 2022 Apr 22.
Understanding how gene regulatory networks (GRNs) control developmental progression is a key to the mechanistic understanding of morphogenesis. The sea urchin larval skeletogenesis provides an excellent platform to tackle this question. In the early stages of sea urchin skeletogenesis, skeletogenic genes are uniformly expressed in the skeletogenic lineage. Yet, during skeletal elongation, skeletogenic genes are expressed in distinct spatial sub-domains. The regulation of differential gene expression during late skeletogenesis is not well understood.
Here we reveal the dynamic expression of the skeletogenic regulatory genes that define a specific regulatory state for each pair of skeletal rods, in the sea urchin Paracentrotus lividus. The vascular endothelial growth factor (VEGF) signaling, essential for skeleton formation, specifically controls the migration of cells that form the postoral and distal anterolateral skeletogenic rods. VEGF signaling also controls the expression of regulatory genes in cells at the tips of the postoral rods, including the transcription factors Pitx1 and MyoD1. Pitx1 activity is required for normal skeletal elongation and for the expression of some of VEGF target genes.
Our study illuminates the fine-tuning of the regulatory system during the transition from early to late skeletogenesis that gives rise to rod-specific regulatory states.
理解基因调控网络(GRNs)如何控制发育进程是理解形态发生机制的关键。海胆幼虫骨骼发生为解决这个问题提供了一个极好的平台。在海胆骨骼发生的早期阶段,骨骼发生基因在骨骼发生谱系中均匀表达。然而,在骨骼伸长过程中,骨骼发生基因在不同的空间亚域中表达。晚期骨骼发生中差异基因表达的调控尚不清楚。
在这里,我们揭示了骨骼发生调节基因的动态表达,这些基因为每个骨骼棒对定义了一个特定的调节状态,在海胆 Paracentrotus lividus 中。血管内皮生长因子(VEGF)信号对于骨骼形成是必不可少的,它特异性地控制形成后口和远端前外侧骨骼发生棒的细胞的迁移。VEGF 信号还控制着后口棒尖端细胞中调节基因的表达,包括转录因子 Pitx1 和 MyoD1。Pitx1 活性对于正常的骨骼伸长和一些 VEGF 靶基因的表达是必需的。
我们的研究阐明了在从早期到晚期骨骼发生的过渡过程中调节系统的精细调整,这导致了棒状特异性调节状态。