在开发过程中,体节在造血干细胞(HSC)的规范中起关键作用。在斑马鱼中,躯体Notch配体Delta-c(Dlc)和Dld,两者均受Wnt16调控,直接指导共享血管前体中的HSC命运。然而,尚不清楚这种信号级联在体节内是如何在空间和时间上调节的。这里,我们在斑马鱼中显示了一个额外的躯体Notch配体,锯齿状2b(Jag2b),诱导细胞间信号传导以驱动wnt16表达。Jag2b在体发生早期激活了分段体节中的Notch信号。jag2b的丢失导致在体节和HSC标记中wnt16的表达减少,runx1在背主动脉,而jag2b的过表达增加。然而,Notch激活的细胞与,但没有重叠,在体节内表达wnt16的细胞,表明额外的信号分子介导了这种细胞间信号转导。我们发现Jag2b驱动的Notch信号诱导efna1b表达,它调节邻近体细胞中wnt16的表达。总的来说,我们提供了先前尚未确定的HSC通过体节特化的时空调控机制的证据。
During development, the somites play a key role in the specification of hematopoietic stem cells (HSCs). In zebrafish, the somitic Notch ligands Delta-c (Dlc) and Dld, both of which are regulated by Wnt16, directly instruct HSC fate in a shared vascular precursor. However, it remains unclear how this signaling cascade is spatially and temporally regulated within somites. Here, we show in zebrafish that an additional somitic Notch ligand,
Jagged 2b (Jag2b), induces intercellular signaling to drive wnt16 expression. Jag2b activated Notch signaling in segmented somites at the early stage of somitogenesis. Loss of jag2b led to a reduction in the expression of wnt16 in the somites and an HSC marker, runx1, in the dorsal aorta, whereas overexpression of jag2b increased both. However, Notch-activated cells were adjacent to, but did not overlap with, wnt16-expressing cells within the somites, suggesting that an additional signaling molecule mediates this intercellular signal transduction. We uncover that Jag2b-driven Notch signaling induces efna1b expression, which regulates wnt16 expression in neighboring somitic cells. Collectively, we provide evidence for previously unidentified spatiotemporal regulatory mechanisms of HSC specification by somites.