[PDF][PDF] Hippocampal neurogenesis requires cell-autonomous thyroid hormone signaling

S Mayerl, H Heuer - Stem Cell Reports, 2020 - cell.com
S Mayerl, H Heuer
Stem Cell Reports, 2020cell.com
Adult hippocampal neurogenesis is strongly dependent on thyroid hormone (TH). Whether
TH signaling regulates this process in a cell-autonomous or non-autonomous manner
remains unknown. To answer this question, we used global and conditional knockouts of the
TH transporter monocarboxylate transporter 8 (MCT8), having first used FACS and
immunohistochemistry to demonstrate that MCT8 is the only TH transporter expressed on
neuroblasts and adult slice cultures to confirm a necessary role for MCT8 in neurogenesis …
Summary
Adult hippocampal neurogenesis is strongly dependent on thyroid hormone (TH). Whether TH signaling regulates this process in a cell-autonomous or non-autonomous manner remains unknown. To answer this question, we used global and conditional knockouts of the TH transporter monocarboxylate transporter 8 (MCT8), having first used FACS and immunohistochemistry to demonstrate that MCT8 is the only TH transporter expressed on neuroblasts and adult slice cultures to confirm a necessary role for MCT8 in neurogenesis. Both mice with a global deletion or an adult neural stem cell-specific deletion of MCT8 showed decreased expression of the cell-cycle inhibitor P27KIP1, reduced differentiation of neuroblasts, and impaired generation of new granule cell neurons, with global knockout mice also showing enhanced neuroblast proliferation. Together, our results reveal a cell-autonomous role for TH signaling in adult hippocampal neurogenesis alongside non-cell-autonomous effects on cell proliferation earlier in the lineage.
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