Developmental gene expression patterns in the brain and liver of Xenopus tropicalis during metamorphosis climax

Abstract

Thyroid hormones (THs) induce metamorphosis in amphibians, causing dynamic changes, whereas mammalian newborns undergo environmental transition from placenta to open air at birth. The similarity between amphibian metamorphosis and the mammalian perinatal periods has been repeatedly discussed. However, a corresponding developmental gene expression analysis has not yet been reported. In this study, we examined the developmental gene expression profiles in the brain and liver of Xenopus tropicalis during metamorphosis climax and compared them to the respective gene expression profiles of newborn rodents. Many upregulated genes identified in the tadpole brain during metamorphosis are also upregulated in the rodent brain during the first three postnatal weeks when the TH surge occurs. The upregulation of some genes in the brain was inhibited in thyroid hormone receptor α (TRα) knockout tadpoles but not in TRβ–knockout tadpoles, implying that brain metamorphosis is mainly mediated by TRα. The expression of some genes was also increased in the liver during metamorphosis climax. Our data suggest that the rodent brain undergoes TH‐dependent remodeling during the first three postnatal weeks as observed in X. tropicalis during the larva‐to‐adult metamorphosis.

Temporal and spatial transcriptomic dynamics across brain development in Xenopus laevis tadpoles

“…Metamorphosis is a significant transitional period in amphibian development, marked by drastic thyroid hormone-driven changes in physiology and gene expression across the body, including the central nervous system ( Kollros and Frieden 1961 ; Yaoita and Nakajima 2018 ). In the amphibians Microhyla fissipes ( Zhao et al 2016 ) and Ambystoma velasci ( Palacios-Martinez et al 2020 ), transcriptomic profiles over the metamorphic period have been collected and compared to illuminate how gene expression changes as metamorphosis proceeds.…”

“…The third stage is the metamorphic climax (NF stages 57/58–66), in which proliferation and neurogenesis fall below even premetamorphic levels ( Thuret et al 2015 ). The metamorphic climax is also significant in that it is thought to parallel many aspects of perinatal mammalian development, including a reorganization of the nervous system accompanying the transition to breathing air and terrestrial life, and a dramatic migration of the eyes to the top of the head resulting in a shift of the visual map in the brain ( Nieuwkoop and Faber 1956 ; Udin and Fisher 1985 ; Udin 1989 ; Holzer and Laudet 2013 ; Yaoita and Nakajima 2018 ). Given these observations, metamorphosis appears to be an important period in Xenopus brain development and elucidating its transcriptional dynamics would help clarify how these significant physiological changes are driven and regulated.…”

Tail Resorption During Metamorphosis in Xenopus Tadpoles

“…TH-dependent metamorphosis is also reported in sea urchin (4), amphioxus (5), and flounder (6) to alter the lifestyle from that of a planktotrophic or free-swimming larva to that of a sessile or benthic adult. The developmental profile of gene expression in the rodent brain during the first 3 postnatal weeks resembles the corresponding profile in the Xenopus brain during the metamorphosis climax, which strongly suggests that the mammalian brain undergoes TH-dependent metamorphosis to adapt to the open-air environment after aquatic (amniotic) life, similar to anuran metamorphosis (7). In amniotes, TH-dependent metamorphosis might have evolved for adapting to environmental change during the rapid transition from amniotic to terrestrial life (8).…”

“…This notion is supported by results demonstrating that the serum of wild-type X. tropicalis frogs contains 6.3 nM T4, which is comparable to the concentration in the X. laevis tadpole featuring a regressing tail during the metamorphosis climax (63). In addition, one of the TH-response genes, TR β, is expressed in the adult brain and liver at a level similar to the late phase of the metamorphosis climax (7). These findings show that the endogenous levels of THs circulating in a frog induce the degeneration of the syngeneic tadpole skin graft.…”

“…Wild-type and TR α-knockout tadpoles show no differences in developmental tail regression during the metamorphosis climax (14–16) in either histological or quantitative gene-expression analysis (16). However, the precocious development of hindlimbs is observed during premetamorphosis before TH secretion (14–16) and the expression levels of several brain genes are reduced at NF stage 61 in TR α-knockout tadpoles (7). The absence of TRα leads to TR β de-repression, accumulation, and subsequent recruitment to the TRE of TR β to repress its expression in the absence of THs (14), but is not enough to bind to the weak TREs.…”