T3 Thyroid Hormone Transporter Crucial To Early Brain Development

A thyroid hormone transporter is crucial for the earliest stages of brain development, according to a study of a region of the developing chicken brain with a layered structure similar to the human cerebral cortex.

Monocarboxylate transporter 8 (MCT8) deficiency in humans results in a rare neurological disorder called Allan-Herndon-Dudley Syndrome. The deficiency prevents thyroid hormones from facilitating proper development of the cortex.

Although a role for MTC8 has been demonstrated at the blood-brain barrier and in the formation of neural circuits, it has not been established at the role of progenitor cells before they differentiate into neuronal and glial cells.

 

MCT8 Expression

Veerle Darras, of the Department of Biology at KU Leuven in Belgium, along with colleagues, investigated the development of the optic tectum in chick embryos, a layered region that shares features with the mammalian cerebral cortex. By genetically modifying MCT8 expression, they found that MCT8-deficient cells failed to migrate to the outer layers of the optic tectum.

In addition, the MCT8 deficiency disrupted the cell cycle and reduced the generation of new cells. Mutations in the MCT8 gene, also known as SLC16A2, provides instructions for making a protein that plays a critical role in the development of the nervous system.

 

Based on their findings, the authors suggest that brain lesions in Allan-Herndon-Dudley Syndrome may originate before birth and treatments may therefore need to be started prenatally as well.

Pieter Vancamp, Marie-Anne Deprez, Michiel Remmerie, Veerle M. Darras
Deficiency of the thyroid hormone transporter MCT8 in neural progenitors impairs cellular processes crucial for early corticogenesis
Journal of Neuroscience 6 November 2017, 1917-17; DOI: 10.1523/JNEUROSCI.1917-17.2017

Image: a section through the optic tectum of a chicken embryo, showing that MCT8-deficient cells (right panel) fail to migrate to their normal position. Credit: Pieter Vancamp