Implication of thyroid hormone signaling in neural crest cells migration: Evidence from thyroid hormone receptor beta knockdown and NH3 antagonist studies

- Altered TH signaling impairs early developmental processes in the amphibian Xenopus.
- Phenotypic manifestations are obtained following NH-3 treatment or THRB knockdown.
- The temporal window of sensitivity encompasses the emergence of neural crest cells.
- Neural crest cell migration but not their induction or specification are compromised.
- Early TH signaling alteration leads to malformations related to neurocristopathies.

Thyroid hormones (TH) have been mainly associated with post-embryonic development and adult homeostasis but few studies report direct experimental evidence for TH function at very early phases of embryogenesis.We assessed the outcome of altered TH signaling on early embryogenesis using the amphibian Xenopus as a model system. Precocious exposure to the TH antagonist NH-3 or impaired thyroid receptor beta function led to severe malformations related to neurocristopathies. These include pathologies with a broad spectrum of organ dysplasias arising from defects in embryonic neural crest cell (NCC) development. We identified a specific temporal window of sensitivity that encompasses the emergence of NCCs. Although the initial steps in NCC ontogenesis appeared unaffected, their migration properties were severely compromised both in vivo and in vitro. Our data describe a role for TH signaling in NCCs migration ability and suggest severe consequences of altered TH signaling during early phases of embryonic development.