Hippocampal Neurogenesis Requires Cell-Autonomous Thyroid Hormone Signaling

Mayerl, Steffen, Heuer, Heike and ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 (2020) Hippocampal Neurogenesis Requires Cell-Autonomous Thyroid Hormone Signaling. Stem Cell Reports, 14 (5). pp. 845-860. ISSN 2213-6711

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Abstract

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.

Item Type: Article
Additional Information: Funding Information: This work was supported by grants from the DFG to S.M. ( MA7212/2-1 ) and H.H. ( HE3418/8-1 within the SPP1629), and by a Wellcome Trust Senior Investigator award (104783/Z/14/Z) and funding from the BBSRC ( BB/L00402X/1 ) to C.ff-C. We thank SCRM animal facility staff (Luke McPhee, Chris Wilson, Lorraine McNeil, John Agnew, and Jamie Kelly) for their excellent help. We are also grateful to Fiona Rossi and Claire Cryer (SCRM FACS facility) and Bertrand Vernay (SCRM imaging facility) for support. Funding Information: This work was supported by grants from the DFG to S.M. (MA7212/2-1) and H.H. (HE3418/8-1 within the SPP1629), and by a Wellcome Trust Senior Investigator award (104783/Z/14/Z) and funding from the BBSRC (BB/L00402X/1) to C.ff-C. We thank SCRM animal facility staff (Luke McPhee, Chris Wilson, Lorraine McNeil, John Agnew, and Jamie Kelly) for their excellent help. We are also grateful to Fiona Rossi and Claire Cryer (SCRM FACS facility) and Bertrand Vernay (SCRM imaging facility) for support.
Uncontrolled Keywords: adult hippocampal neurogenesis,mct8,neuroblasts,p27kip1,slc16a2,t3,t4,thyroid hormone,biochemistry,genetics,developmental biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 19 Jul 2022 14:30
Last Modified: 25 Sep 2022 03:13
URI: https://ueaeprints.uea.ac.uk/id/eprint/86622
DOI: 10.1016/j.stemcr.2020.03.014

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