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Thyroid Hormone Transporter Deficiency in Mice Impacts Multiple Stages of GABAergic Interneuron Development

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Bibliographic Details
Title: Thyroid Hormone Transporter Deficiency in Mice Impacts Multiple Stages of GABAergic Interneuron Development
Authors: Veerle Darras, Heike Heuer, Eva Salveridou, Anita Boelen, Jiesi Chen, Steffen Mayerl
Source: Cereb Cortex
Publisher Information: Oxford University Press (OUP), 2021.
Publication Year: 2021
Subject Terms: Monocarboxylic Acid Transporters, 0301 basic medicine, Thyroid Hormones, 1702 Cognitive Sciences, Medizin, METABOLISM, Mice, 03 medical and health sciences, Interneurons, PARVALBUMIN IMMUNOREACTIVITY, Slco1c1, Animals, Hedgehog Proteins, AXIS, Symporters/genetics [MeSH], Hedgehog Proteins/metabolism [MeSH], In Situ Hybridization, Fluorescence, Symporters/metabolism, Symporters/metabolism [MeSH], Thyroid Hormones/metabolism [MeSH], Interneurons/metabolism, Monocarboxylic Acid Transporters/metabolism [MeSH], Monocarboxylic Acid Transporters/genetics [MeSH], Animals [MeSH], Monocarboxylic Acid Transporters/metabolism, Symporters/genetics, Monocarboxylic Acid Transporters/genetics, Mice [MeSH], Hedgehog Proteins/metabolism, Thyroid Hormones/metabolism, Interneurons/metabolism [MeSH], In Situ Hybridization, Fluorescence [MeSH], SPECIFICATION, Parvalbumin, Science & Technology, PROGENITORS, Symporters, MUTATIONS, Neurosciences, Experimental Psychology, thyroid hormone, 3. Good health, GABAergic interneurons, Oatp1c1, 1701 Psychology, 5202 Biological psychology, MCT8, ORIGINS, Mct8, LACKING, CELLS, 3209 Neurosciences, 5204 Cognitive and computational psychology, Allan Herndon Dudley Syndrome, Original Article, Neurosciences & Neurology, Slc16a2, 1109 Neurosciences, Life Sciences & Biomedicine
Description: Cortical interneuron neurogenesis is strictly regulated and depends on the presence of thyroid hormone (TH). In particular, inhibitory interneurons expressing the calcium binding protein Parvalbumin are highly sensitive toward developmental hypothyroidism. Reduced numbers of Parvalbumin-positive interneurons are observed in mice due to the combined absence of the TH transporters Mct8 and Oatp1c1. To unravel if cortical Parvalbumin-positive interneurons depend on cell-autonomous action of Mct8/Oatp1c1, we compared Mct8/Oatp1c1 double knockout (dko) mice to conditional knockouts with abolished TH transporter expression in progenitors of Parvalbumin-positive interneurons. These conditional knockouts exhibited a transient delay in the appearance of Parvalbumin-positive interneurons in the early postnatal somatosensory cortex while cell numbers remained permanently reduced in Mct8/Oatp1c1 dko mice. Using fluorescence in situ hybridization on E12.5 embryonic brains, we detected reduced expression of sonic hedgehog signaling components in Mct8/Oatp1c1 dko embryos only. Moreover, we revealed spatially distinct expression patterns of both TH transporters at brain barriers at E12.5 by immunofluorescence. At later developmental stages, we uncovered a sequential expression of first Oatp1c1 in individual interneurons and then Mct8 in Parvalbumin-positive subtypes. Together, our results point to multiple cell-autonomous and noncell-autonomous mechanisms that depend on proper TH transport during cortical interneuron development.
Document Type: Article
Other literature type
Language: English
ISSN: 1460-2199
1047-3211
DOI: 10.1093/cercor/bhab211
Access URL: https://academic.oup.com/cercor/advance-article-pdf/doi/10.1093/cercor/bhab211/39508242/bhab211.pdf
https://pubmed.ncbi.nlm.nih.gov/34339499
https://pubmed.ncbi.nlm.nih.gov/34339499/
https://pure.amsterdamumc.nl/en/publications/4e6be8d9-b797-4eda-9802-66e8b2c051dc
https://doi.org/10.1093/cercor/bhab211
https://repository.publisso.de/resource/frl:6475590
Rights: CC BY NC
URL: http://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Accession Number: edsair.doi.dedup.....26e062fcf1f9e24269d3d9aaa4f92b74
Database: OpenAIRE
Description
Abstract:Cortical interneuron neurogenesis is strictly regulated and depends on the presence of thyroid hormone (TH). In particular, inhibitory interneurons expressing the calcium binding protein Parvalbumin are highly sensitive toward developmental hypothyroidism. Reduced numbers of Parvalbumin-positive interneurons are observed in mice due to the combined absence of the TH transporters Mct8 and Oatp1c1. To unravel if cortical Parvalbumin-positive interneurons depend on cell-autonomous action of Mct8/Oatp1c1, we compared Mct8/Oatp1c1 double knockout (dko) mice to conditional knockouts with abolished TH transporter expression in progenitors of Parvalbumin-positive interneurons. These conditional knockouts exhibited a transient delay in the appearance of Parvalbumin-positive interneurons in the early postnatal somatosensory cortex while cell numbers remained permanently reduced in Mct8/Oatp1c1 dko mice. Using fluorescence in situ hybridization on E12.5 embryonic brains, we detected reduced expression of sonic hedgehog signaling components in Mct8/Oatp1c1 dko embryos only. Moreover, we revealed spatially distinct expression patterns of both TH transporters at brain barriers at E12.5 by immunofluorescence. At later developmental stages, we uncovered a sequential expression of first Oatp1c1 in individual interneurons and then Mct8 in Parvalbumin-positive subtypes. Together, our results point to multiple cell-autonomous and noncell-autonomous mechanisms that depend on proper TH transport during cortical interneuron development.
ISSN:14602199
10473211
DOI:10.1093/cercor/bhab211