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

Abstract

There is presently a very limited understanding of the mechanisms that underlie the evolution of new cell types. The skeleton-forming primary mesenchyme cells (PMCs) of euechinoid sea urchins, derived from the micromeres of the 16-cell embryo, are an example of a recently evolved cell type. All adult echinoderms have a calcite-based endoskeleton, a synapomorphy of the Ambulacraria. Only euechinoids have a micromere-PMC lineage, however, which evolved through the co-option of the adult skeletogenic program into the embryo. During normal development, PMCs alone secrete the embryonic skeleton. Other mesoderm cells, known as blastocoelar cells (BCs), have the potential to produce a skeleton, but a PMC-derived signal ordinarily prevents these cells from expressing a skeletogenic fate and directs them into an alternative developmental pathway. Recently, it was shown that vascular endothelial growth factor (VEGF) signaling plays an important role in PMC differentiation and is part of a conserved program of skeletogenesis among echinoderms. Here, we report that VEGF signaling, acting through ectoderm-derived VEGF3 and its cognate receptor, VEGF receptor (VEGFR)-10-Ig, is also essential for the deployment of the skeletogenic program in BCs. This VEGF-dependent program includes the activation of aristaless-like homeobox 1 (alx1), a conserved transcriptional regulator of skeletogenic specification across echinoderms and an example of a “terminal selector” gene that controls cell identity. We show that PMCs control BC fate by sequestering VEGF3, thereby preventing activation of alx1 and the downstream skeletogenic network in BCs. Our findings provide an example of the regulation of early embryonic cell fates by direct competition for a secreted signaling ligand, a developmental mechanism that has not been widely recognized. Moreover, they reveal that a novel cell type evolved by outcompeting other embryonic cell lineages for an essential signaling ligand that regulates the expression of a gene controlling cell identity.

Gene regulation of adult skeletogenesis in starfish and modifications during gene network co-option

“…Therefore, we propose that the upstream system was changed from the nutrient-Vegf signaling pathway to a double-negative gate with Pmar1 and an unknown repressor when the larval skeleton was acquired by co-option of the adult skeletogenic system. It should be noted that, based on the experiments using PMC-removed euechinoid embryos, the recent study also proposed that the regulation of alx1 by Vegf signaling is ancestral mode for skeletogenic cell formation in the echinoderm 36 .…”

The Evolution of Biomineralization through the Co-Option of Organic Scaffold Forming Networks

“…Relatedly, when the skeletogenic cells are removed from the sea urchin embryo, some of the oral NSM cells differentiate into skeletogenic cells and generate a skeleton [ 107 , 108 , 109 ]. This trans-differentiation occurs in the blastocoelar cells that express low levels of VEGFR which enable them to respond to VEGF signaling when the skeletogenic cells are removed and transform into skeletogenic cells [ 110 ]. Thus, in the sea urchin embryo, some regulatory genes are shared between the skeletogenic and blastocoelar GRNs and the blastocoelar cells can switch into skeletogenic fate through the activation of VEGF signaling.…”

“…Hence, both the endothelial GRN and the echinoderm skeletogenic GRN drive a process of tubulogenesis. Additionally, both GRNs are very close to hemocyte generating GRNs: The echinoderm skeletogenic GRN is highly similar to the NSM GRN that drives hemocytes specification and the hemocytes can re-differentiate into skeletogenic cells, depending on VEGF signaling ( Figure 3 D [ 110 ]). As explained above, a close relationship between hematopoeitic cells and endothelial cells as well as the ability to trans-differentiate between these fates exists in vertebrates [ 200 ].…”

Transcription Factors of the Alx Family: Evolutionarily Conserved Regulators of Deuterostome Skeletogenesis

“…Furthermore, experimental ablation of PMCs leads to the activation of alx1 and downstream components of the skeletogenic GRN by non-skeletogenic mesoderm (NSM) cells, which ultimately reform a larval skeleton (Ettensohn et al, 2007). The ectopic activation of alx1 is essential for NSM cells to acquire skeletogenic properties, although this activation occurs by a mechanism distinct from that which normally operates in the large micromeres (Oliveri et al, 2008;Sharma and Ettensohn, 2011;Ettensohn and Adomako-Ankomah, 2019). Remarkably, the removal of NSM cells via microsurgical removal of the archenteron as well as PMCs results in the activation of alx1 and formation of a skeleton by presumptive endoderm cells (Sharma and Ettensohn, 2011).…”