Maternal Thyroid Hormone Increases Neural Cell Diversity During Zebrafish Spinal Cord Neurodevelopment

Maternally derived thyroid hormone (MT3) is a fundamental factor for vertebrate neurodevelopment. In humans, mutations on the T3 exclusive transporter monocarboxylic acid transporter 8 (MCT8) lead to the Allan-Herndon-Dudley syndrome (AHDS). Patients with AHDS present severe underdevelopment of the central nervous system with cognitive and locomotory consequences. Functional impairment of the zebrafish T3 exclusive membrane transporter MCT8 has been shown to phenocopy the symptoms observed in human patients with AHDS, thus providing an outstanding animal model to study this human condition. In this zebrafish model, MT3 acts as an integrator of different key developmental pathways during zebrafish neurodevelopment. Here we expand this knowledge by determining the developmental time of action of MT3 that occurs in very defined temporal intervals during zebrafish neurodevelopment. We have determined that MT3 is not involved in neural specification but is fundamental for developing particular neural progenitors and the consequent neural lineages that originate from them. Our data provide evidence that MT3 achieves this likely by modulation NOTCH signalling in a cell non-autonomous way. The findings show that MT3 expands the cell diversity output of neural progenitor cells, establishing a cellular background behind human AHDS and inherited limited CNS development.