Possible cooption of a VEGF-driven tubulogenesis program for biomineralization in echinoderms

Abstract

Biomineralization is the process by which living organisms use minerals to form hard structures that protect and support them. Biomineralization is believed to have evolved rapidly and independently in different phyla utilizing preexisting components. The mechanistic understanding of the regulatory networks that drive biomineralization and their evolution is far from clear. Sea urchin skeletogenesis is an excellent model system for studying both gene regulation and mineral uptake and deposition. The sea urchin calcite spicules are formed within a tubular cavity generated by the skeletogenic cells controlled by vascular endothelial growth factor (VEGF) signaling. The VEGF pathway is essential for biomineralization in echinoderms, while in many other phyla, across metazoans, it controls tubulogenesis and vascularization. Despite the critical role of VEGF signaling in sea urchin spiculogenesis, the downstream program it activates was largely unknown. Here we study the cellular and molecular machinery activated by the VEGF pathway during sea urchin spiculogenesis and reveal multiple parallels to the regulation of vertebrate vascularization. Human VEGF rescues sea urchin VEGF knockdown, vesicle deposition into an internal cavity plays a significant role in both systems, and sea urchin VEGF signaling activates hundreds of genes, including biomineralization and interestingly, vascularization genes. Moreover, five upstream transcription factors and three signaling genes that drive spiculogenesis are homologous to vertebrate factors that control vascularization. Overall, our findings suggest that sea urchin spiculogenesis and vertebrate vascularization diverged from a common ancestral tubulogenesis program, broadly adapted for vascularization and specifically coopted for biomineralization in the echinoderm phylum.

The origin of animal body plans: a view from fossil evidence and the regulatory genome

“…From this, we expect that morphogenetic patterning systems have been conserved within major clades (such as within Panarthropoda) but are likely to have arisen independently between major clades. Returning to biomineralization, within mollusks, for example, it appears to have arisen independently in bivalves and gastropods (Jackson et al, 2010), while biomineralization in echinoids involves the co-option of an ancestral VEGF GRN involved in tubulogenesis (Morgulis et al, 2019). significantly capitalized on some of these new capabilities.…”

Developmental transcriptomes of the sea star, Patiria miniata, illuminate how gene expression changes with evolutionary distance

“…Echinoderms have two types of feeding larvae: the pluteus-like larvae of sea urchins and brittle stars, and the auricularia-like larvae of sea cucumbers and sea stars 2 . Of these, the sea urchin and the sea star had been extensively studied both for their embryogenesis and their gene regulatory networks 3–13 . Sea urchins and sea stars diverged from their common ancestor about 500 million years ago, yet their endoderm lineage and the gut morphology show high similarity between their embryos 6 .…”

The evolution of a new cell type was associated with competition for a signaling ligand

“…During gastrulation, vegf3 is expressed at high levels (peak expression > 1,200 transcripts/embryo), whereas vegf and vegf2 are expressed at very low levels or not at all (<20 transcripts/embryo) [22]. vegf3 is expressed in localized regions of the ectoderm and functions along with vegfr-10-Ig as an essential mediator of PMC migration and skeletogenesis [9–13]. VEGF3 was therefore a likely candidate for the ligand that interacted with VEGFR-10-Ig to activate the skeletogenic GRN in transfating BCs.…”

“…Ancient roles for alx1 , vegf3 , and vegfr-10-Ig in echinoderm skeletogenesis are inferred from the conserved expression of these genes in adult and embryonic skeletogenic centers in multiple echinoderm clades and from experimental perturbations of gene function in echinoid and holothuroid embryos (see references in [3]). Red lines are inferred from experimentally determined inputs of VEGF3 signaling into vegfr-10-Ig and biomineralization genes in euechinoid PMCs [9,11,13]. The brokenness of the lines indicates that intervening transcription factors have not been identified.…”

“…In euechinoid sea urchins, although VEGF signaling is not involved in the maternally entrained, cell-autonomous specification of the micromere-PMC lineage, it plays an important role later in embryogenesis when PMC migration and skeletogenesis come under the regulatory influence of VEGF3 produced by ectoderm cells [9–12]. Morgulis and coworkers [13] recently used whole-embryo RNA sequencing (RNA-seq) to show that VEGF signaling regulates hundreds of genes, including many biomineralization genes expressed selectively by PMCs, and they propose that VEGF regulates an ancient program of tubulogenesis shared by echinoderms and vertebrates.…”