Corticosterone Is Essential for Survival Through Frog Metamorphosis

Area of Science:

• Endocrinology
• Developmental Biology
• Genetics

Background:

• Thyroid hormone (TH) is crucial for amphibian metamorphosis.
• Corticosterone (CORT) is known to enhance TH signaling and accelerate metamorphosis.
• The essentiality of CORT for metamorphosis has been challenging to ascertain prior to gene-editing technologies.

Purpose of the Study:

• To investigate the requirement of corticosterone (CORT) in frog metamorphosis using gene-editing technology.
• To determine the role of CORT in mediating thyroid hormone (TH) signaling during metamorphic progression.

Main Methods:

• Utilized transcription activator-like effector nuclease (TALEN) gene disruption to knock out proopiomelanocortin (pomc) in Xenopus tropicalis, thereby disrupting CORT production.
• Assessed plasma CORT levels, expression of CORT-response and TH-response genes (ush1g, klf9, thrb), and developmental rates in pomc mutant tadpoles.
• Administered exogenous TH and CORT to rescue mutant phenotypes and survival.

Main Results:

• Pomc mutant tadpoles exhibited reduced plasma CORT peaks, decreased expression of CORT- and TH-response genes, and impaired growth and development.
• Mutants showed diminished TH response gene induction and slower morphological changes when treated with exogenous TH.
• Pomc mutants invariably died during tail resorption, a lethal phenotype rescued by exogenous CORT or TH.

Conclusions:

• Corticosterone (CORT) is essential for Xenopus tropicalis metamorphosis, impacting TH signaling, development, and survival.
• The CORT-dependent enhancement of TH signaling is critical for ensuring functional organ transformation and preventing mortality during the nonfeeding metamorphic transition.