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The skeleton-forming cells of sea urchins and other echinoderms have been studied by developmental biologists as models of cell specification and morphogenesis for many decades. The gene regulatory network (GRN) deployed in the embryonic skeletogenic cells of euechinoid sea urchins is one of the best understood in any developing animal. Recent comparative studies have leveraged the information contained in this GRN, bringing renewed attention to the diverse patterns of skeletogenesis within the phylum and the evolutionary basis for this diversity. The homeodomain-containing transcription factor, Alx1, was originally shown to be a core component of the skeletogenic GRN of the sea urchin embryo. Alx1 has since been found to be key regulator of skeletal cell identity throughout the phylum. As such, Alx1 is currently serving as a lens through which multiple developmental processes are being investigated. These include not only GRN organization and evolution, but also cell reprogramming, cell type evolution, and the gene regulatory control of morphogenesis. This review summarizes our current state of knowledge concerning Alx1 and highlights the insights it is yielding into these important developmental and evolutionary processes.
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Architecture and evolution of the cis-regulatory system of the echinoderm kirrelL gene
The gene regulatory network (GRN) that underlies echinoderm skeletogenesis is a prominent model of GRN architecture and evolution. KirrelL is an essential downstream effector gene in this network and encodes an Ig-superfamily protein required for the fusion of skeletogenic cells and the formation of the skeleton. In this study, we dissected the transcriptional control region of the kirrelL gene of the purple sea urchin, Strongylocentrotus purpuratus . Using plasmid- and bacterial artificial chromosome-based transgenic reporter assays, we identified key cis -regulatory elements (CREs) and transcription factor inputs that regulate Sp-kirrelL , including direct, positive inputs from two key transcription factors in the skeletogenic GRN, Alx1 and Ets1. We next identified kirrelL cis -regulatory regions from seven other echinoderm species that together represent all classes within the phylum. By introducing these heterologous regulatory regions into developing sea urchin embryos we provide evidence of their remarkable conservation across ~500 million years of evolution. We dissected in detail the kirrelL regulatory region of the sea star, Patiria miniata , and demonstrated that it also receives direct inputs from Alx1 and Ets1. Our findings identify kirrelL as a component of the ancestral echinoderm skeletogenic GRN. They support the view that GRN subcircuits, including specific transcription factor–CRE interactions, can remain stable over vast periods of evolutionary history. Lastly, our analysis of kirrelL establishes direct linkages between a developmental GRN and an effector gene that controls a key morphogenetic cell behavior, cell–cell fusion, providing a paradigm for extending the explanatory power of GRNs.
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- Award ID(s):
- 2004952
- PAR ID:
- 10342094
- Date Published:
- Journal Name:
- eLife
- Volume:
- 11
- ISSN:
- 2050-084X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.7554/eLife.72834
