Thyroid hormone-induced cell death in sea urchin metamorphic development

Abstract

Thyroid hormones (THs) are important regulators of development, metabolism, and homeostasis in metazoans. Specifically, they have been shown to regulate the metamorphic transitions of vertebrates and invertebrates alike. Indirectly developing sea urchin larvae accelerate the formation of juvenile structures in response to thyroxine (T4) treatment, while reducing their larval arm length. The mechanisms underlying larval arm reduction are unknown and we hypothesized that programmed cell death (PCD) is linked to this process. To test this hypothesis, we measured larval arm retraction in response to different THs (T4, T3, rT3, Tetrac) and assessed cell death in larvae using three different methods (TUNEL, YO-PRO-1 and Caspase-3 activity) in the sea urchin Strongylocentrotus purpuratus. We also compared the extent of PCD in response to TH treatment before and after the invagination of the larval ectoderm, which marks the initiation of juvenile development in larval sea urchin species. We found that T4 treatment results in the strongest reduction of larval arms but detected a significant increase of PCD in response to T4, T3 and Tetrac in post-ingression but not pre-ingression larvae. As post-ingression larvae have initiated metamorphic development and therefore allocate resources to both, larval and the juvenile structures, these results provide evidence that THs regulate larval development differentially via PCD. PCD in combination with cell proliferation likely has a key function in sea urchin development.

Thyroid hormone membrane receptor binding and transcriptional regulation in the sea urchin Strongylocentrotus purpuratus

“…Previous research has shown that THs induce apoptosis in sea urchins (38) and that the histaminergic system may be crucial for regulation of metamorphosis and settlement, with histamine accelerating metamorphic competence but inhibiting settlement and apoptosis in the larval arms (52,122). We find that in postrudiment larvae (27d), T4 significantly increased histamine receptor expression, while in pre-rudiment larvae (23d), T4 increased expression of histamine-metabolizing enzymes.…”

“…Apoptosis in particular plays an important role in morphogenesis during sea urchin larval development (38,(99)(100)(101). We previously found that THs regulate larval arm retraction via programmed cell death in sea urchin larvae, with increased levels of caspase 3/7 activation and apoptosis (38). In this transcriptome analysis, we find that caspase gene expression was not affected by THs.…”

“…PCD is a critical process in both chordate and non-chordate metamorphosis (reviewed in 98). Apoptosis in particular plays an important role in morphogenesis during sea urchin larval development (38,(99)(100)(101). We previously found that THs regulate larval arm retraction via programmed cell death in sea urchin larvae, with increased levels of caspase 3/7 activation and apoptosis (38).…”

Shared regulatory function of non-genomic thyroid hormone signaling in echinoderm skeletogenesis

“…Taylor and Heyland (2017) suggested that sea urchin skeletogenesis is regulated by thyroid hormones via a non-genomic integrin-mediated MAPK cascade triggered by direct TH binding to skeletogenic mesenchyme cells. Additionally, Wynen et al (2022) demonstrated a role for THs regulating apoptosis in metamorphic development. However, it is unclear if TH signaling and its involvement in skeletogenesis is limited to S. purpuratus larvae, or if it can be generalized to other sea urchins and echinoderms.…”

“…T4 has been shown to accelerate metamorphic development in echinoderms and molluscs (Carpizo-Ituarte, 1993; Chino et al, 1994;Fukazawa et al, 2001;Heyland et al, 2004Heyland et al, , 2006Hodin et al, 2001;Johnson, 1998;Johnson & Cartwright, 1996;Saito et al, 1998). Evidence suggests that these mechanisms may rely on the nuclear hormone receptor-mediated pathway (Huang et al, 2015;Taylor et al, 2023) and that THR may regulate apoptosis and skeletogenesis in sea urchins (Taylor et al, 2023;Wynen et al, 2022). Additionally, embryonic and larval sea urchin skeletogenesis may be regulated by the TH integrin-mediated pathway (Taylor & Heyland, 2018).…”