Thyroid Hormones and Brain Development: A Focus on the Role of Mitochondria as Regulators of Developmental Time

Thyroid hormones (TH) regulate metabolism in a homeostatic state in an adult organism. During the prenatal period, prior to establishment of homeostatic mechanisms, TH assume additional functions as key regulators of brain development. Here, we focus on reviewing the role of TH in orchestrating cellular dynamics in a developing brain. We provide evidence that developmental roles of the hormones are predominantly mediated by non-genomic mitochondrial effects of TH due to attenuation of genomic effects of TH that antagonise non-genomic impacts. We argue that the key function of TH signalling during brain development is to orchestrate the tempo of self-organisation of neural progenitor cells. Further, evidence is provided that major neurodevelopmental consequences of hypothyroidism stem from an altered tempo of cellular self-organisation.