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

Miri Morgulis, Tsvia Gildor, Modi Roopin, Noa Sher, Assaf Malik, Maya Lalzar, Monica Dines, Shlomo Ben-Tabou de-Leon, Lama Khalaily, Smadar Ben-Tabou de-Leon

Research output: Contribution to journalArticlepeer-review


The sea urchin calcite spicules and vertebrate blood vessels are quite distinct in their function, yet both have a tubular structure and are controlled by the vascular endothelial growth factor (VEGF) pathway. Here we study the downstream program by which VEGF signaling drives sea urchin spiculogenesis and find remarkable similarities to the control of vertebrate vascularization. The similarities are observed both in the upstream gene regulatory network, in the downstream effector genes, and the cellular processes that VEGF signaling controls at the site of the calcite spicule formation. We speculate that sea urchin spiculogenesis and vertebrate vascularization diverged from a common ancestral tubulogenesis program that was uniquely coopted for biomineralization in the echinoderm phylum.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.
Original languageEnglish
Pages (from-to)12353-12362
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - 2019

Bibliographical note

Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.


  • Biomineralization
  • Evolution
  • Gene regulatory networks
  • Tubulogenesis
  • VEGF signaling

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Possible cooption of a VEGF-driven tubulogenesis program for biomineralization in echinoderms'. Together they form a unique fingerprint.

Cite this