Absence of Both Thyroid Hormone Transporters MCT8 and OATP1C1 Impairs Neural Stem Cell Fate in the Adult Mouse Subventricular Zone

Cristina Luongo, Lucile Butruille, Anthony Sébillot, Karine Le Blay, Markus Schwaninger, Heike Heuer, Barbara A. Demeneix, Sylvie Remaud*

*Corresponding author for this work

Abstract

Adult neural stem cell (NSC) generation in vertebrate brains requires thyroid hormones (THs). How THs enter the NSC population is unknown, although TH availability determines proliferation and neuronal versus glial progenitor determination in murine subventricular zone (SVZ) NSCs. Mice display neurological signs of the severely disabling human disease, Allan-Herndon-Dudley syndrome, if they lack both MCT8 and OATP1C1 transporters, or MCT8 and deiodinase type 2. We analyzed the distribution of MCT8 and OATP1C1 in adult mouse SVZ. Both are strongly expressed in NSCs and at a lower level in neuronal cell precursors but not in oligodendrocyte progenitors. Next, we analyzed Mct8/Oatp1c1 double-knockout mice, where brain uptake of THs is strongly reduced. NSC proliferation and determination to neuronal fates were severely affected, but not SVZ-oligodendroglial progenitor generation. This work highlights how tight control of TH availability determines NSC function and glial-neuron cell-fate choice in adult brains.

Original languageEnglish
JournalStem Cell Reports
Volume16
Issue number2
Pages (from-to)337-353
Number of pages17
ISSN2213-6711
DOIs
Publication statusPublished - 09.02.2021

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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