Heterochronic activation of VEGF signaling and the evolution of the skeleton in echinoderm pluteus larvae

Abstract

The evolution of the echinoderm larval skeleton was examined from the aspect of interactions between skeletogenic mesenchyme cells and surrounding epithelium. We focused on vascular endothelial growth factor (VEGF) signaling, which was reported to be essential for skeletogenesis in sea urchin larvae. Here, we examined the expression patterns of vegf and vegfr in starfish and brittle stars. During starfish embryogenesis, no expression of either vegfr or vegf was detected, which contrast with previous reports on the expression of starfish homologs of sea urchin skeletogenic genes, including Ets, Tbr, and Dri. In later stages, when adult skeletogenesis commenced, vegfr and vegf expression were upregulated in skeletogenic cells and in the adjacent epidermis, respectively. These expression patterns suggest that heterochronic activation of VEGF signaling is one of the key molecular evolutionary steps in the evolution of the larval skeleton. The absence of vegf or vegfr expression during early embryogenesis in starfish suggests that the evolution of the larval skeleton requires distinct evolutionary changes, both in mesoderm cells (activation of vegfr expression) and in epidermal cells (activation of vegf expression). In brittle stars, which have well-organized skeletons like the sea urchin, vegfr and vegf were expressed in the skeletogenic mesenchyme and the overlying epidermis, respectively, in the same manner as in sea urchins. Therefore, the distinct activation of vegfr and vegf may have occurred in two lineages, sea urchins and brittle stars.

Signal-dependent regulation of the sea urchin skeletogenic gene regulatory network

“…Thus, the cell-autonomous phase of the regulation of the skeletogenic GRN is also likely to be derived, and the later, signaldependent phase of GRN regulation may more closely resemble the ancestral program of skeletogenic specification in the phylum. This program likely underwent repeated heterochronic shifts during echinoid evolution (Ettensohn, 2009(Ettensohn, , 2013, but features of the ancestral program may be gleaned from studies on skeletogenic specification in echinoderms that lack micromeres and form skeletal elements much later in development, such as cidaroid sea urchins (Yamazaki et al, 2012) and sea stars (Morino et al, 2012).…”

Growth factors and early mesoderm morphogenesis: Insights from the sea urchin embryo

“…In brittle stars, which form an embryonic endoskeleton, a vegf3 ortholog is expressed during early embryogenesis in a ring‐like pattern which then resolves into two domains of ectoderm, as seen in L. variegatus . In contrast, vegf3 is not expressed in sea star embryos, which lack an endoskeleton, though this gene is expressed at late larval stages in epithelial cells that overlie the primordia of the adult skeleton (Morino et al ., ). These comparative studies point to an important, conserved role of VEGF signaling in echinoderm skeletogenesis and suggest that evolutionary modifications in VEGF expression played a role in the appearance of new patterns of skeletogenesis within the phylum.…”

Growth factor-mediated mesodermal cell guidance and skeletogenesis during sea urchin gastrulation

“…Recent work suggests that evolutionary shifts in VEGF3 expression have been associated with changing patterns of skeletogenesis within the phylum (Morino et al, 2012). In contrast to the highly conserved function of VEGF3, the role of FGFA may vary among species, as this molecule has been implicated in PMC migration and skeletogenesis in P. lividus (Röttinger et al, 2008).…”