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Metamorphic gene regulation programs in Xenopus tropicalis tadpole brain
Samhitha Raj1, Christopher J Sifuentes1, Yasuhiro Kyono2
1Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
Plos One
|June 29, 2023
Summary
Thyroid hormone (TH) drives amphibian metamorphosis by regulating gene expression. This study reveals genome-wide changes in the tadpole brain during natural metamorphosis, identifying key genes and potential limitations of short-term TH treatments.
Area of Science:
- Developmental Biology
- Neuroscience
- Endocrinology
Background:
- Amphibian metamorphosis is a complex process orchestrated by thyroid hormone (TH).
- TH acts by binding to thyroid hormone receptors (TRs), which regulate gene expression programs essential for morphogenesis.
- Previous studies primarily used exogenous TH in premetamorphic tadpoles, limiting understanding of natural metamorphic gene regulation.
Purpose of the Study:
- To comprehensively analyze genome-wide gene expression changes in the *Xenopus tropicalis* tadpole brain during spontaneous metamorphosis.
- To identify direct TH target genes in the brain during metamorphosis using TR chromatin immunoprecipitation sequencing (ChIP-seq).
- To compare gene expression dynamics during natural metamorphosis with those induced by acute exogenous TH treatment.
Main Methods:
- RNA sequencing was performed on *Xenopus tropicalis* tadpole brains at four distinct stages of spontaneous metamorphosis.
- Chromatin immunoprecipitation sequencing (ChIP-seq) was employed to map TR binding sites across the genome.
- Gene expression data from spontaneous metamorphosis were compared with data from tadpoles treated with exogenous TH.
Main Results:
- The mRNA levels of 26% of protein-coding genes were altered during metamorphosis, with roughly equal numbers upregulated and downregulated.
- TRs directly regulated 24% of genes showing expression changes during metamorphosis.
- Genes involved in neural development, cell signaling, and synaptic function were upregulated, while cell cycle and stem cell genes were downregulated, reflecting a shift towards adult brain characteristics.
Conclusions:
- This study provides a foundational molecular atlas of tadpole brain metamorphosis, detailing dynamic gene expression shifts.
- The findings reveal a transition from neural structure formation to neural differentiation and maturation characteristic of the adult brain.
- Results highlight potential discrepancies between gene regulation observed during spontaneous metamorphosis and that induced by short-term exogenous TH exposure.
