Abstract
Angioblasts that form the major axial blood vessels of the dorsal aorta and cardinal vein migrate toward the embryonic midline from distant lateral positions. Little is known about what controls the precise timing of angioblast migration and their final destination at the midline. Using zebrafish, we found that midline angioblast migration requires neighboring tissue rearrangements generated by somite morphogenesis. The somitic shape changes cause the adjacent notochord to separate from the underlying endoderm, creating a ventral midline cavity that provides a physical space for the angioblasts to migrate into. The anterior to posterior progression of midline angioblast migration is facilitated by retinoic acid-induced anterior to posterior somite maturation and the subsequent progressive opening of the ventral midline cavity. Our work demonstrates a critical role for somite morphogenesis in organizing surrounding tissues to facilitate notochord positioning and angioblast migration, which is ultimately responsible for creating a functional cardiovascular system.
Highlights
Wild-type angioblasts migrated to the midline in a manner consistent with previously described research (Figure 1A, Video 1) (Helker et al, 2015; Jin et al, 2005; Kohli et al, 2013)
Quantification of fluorescence percentage in the chimeric regions of the somites showed statistical significance between wild-type and tg(HS:dnRAR) (Figure 2J, Figure 2-source data 2). This indicates that the somites are the principal tissue required for retinoic acid (RA) signaling mediated midline angioblast migration. 228 The somitic mesoderm is required for angioblast migration to the midline. 229 230 To follow up the somite and notochord targeted transplant results, we examined midline 231 angioblast migration in embryos where these tissues are absent
We were able to confirm that the somitic mesoderm was required for angioblast migration by examining tbx16 mutants, which have a lack of somites caused by EMT defects (Goto et al, 2017; Ho and Kane, 1990; Manning and Kimelman, 2015; Row et al, 2011)
Summary
55 Early organismal development relies on a variety of tissues that collectively organize into a functional body plan. At the same time that somites are changing shape, endothelial progenitors called angioblasts arise in the lateral plate mesoderm and migrate to the midline of the embryo to form the axial vasculature (Jin et al, 2005). The requirement of notochord specification for angioblast migration suggested that the notochord may act to attract angioblasts to the midline This model was further explored when a notochord-derived secreted factor named apela ( known as toddler/elabela) was discovered (Chng et al., 2013; Freyer et al, 2017; Helker et al, 2015; Pauli et al, 2014). Noto loss of function causes morphological changes that could interfere with angioblast migration, including a broad expansion of somite tissue near the developing blood vessels (Halpern et al, 1995). This evidence places somite131 maturation as a critical event that is required for NES and the development of the axial vasculature
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