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Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration

Previous studies demonstrated specific expression of transcription factor Tbr2 in unipolar brush cells (UBCs) of the cerebellum during development and adulthood. To further study UBCs and the role of Tbr2 in their development we examined UBC morphology in transgenic mouse lines (reporter and lineage...

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Autores principales: McDonough, Ashley, Elsen, Gina E., Daza, Ray M., Bachleda, Amelia R., Pizzo, Donald, DelleTorri, Olivia M., Hevner, Robert F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820753/
https://www.ncbi.nlm.nih.gov/pubmed/33488348
http://dx.doi.org/10.3389/fnins.2020.598548
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author McDonough, Ashley
Elsen, Gina E.
Daza, Ray M.
Bachleda, Amelia R.
Pizzo, Donald
DelleTorri, Olivia M.
Hevner, Robert F.
author_facet McDonough, Ashley
Elsen, Gina E.
Daza, Ray M.
Bachleda, Amelia R.
Pizzo, Donald
DelleTorri, Olivia M.
Hevner, Robert F.
author_sort McDonough, Ashley
collection PubMed
description Previous studies demonstrated specific expression of transcription factor Tbr2 in unipolar brush cells (UBCs) of the cerebellum during development and adulthood. To further study UBCs and the role of Tbr2 in their development we examined UBC morphology in transgenic mouse lines (reporter and lineage tracer) and also examined the effects of Tbr2 deficiency in Tbr2 (MGI: Eomes) conditional knock-out (cKO) mice. In Tbr2 reporter and lineage tracer cerebellum, UBCs exhibited more complex morphologies than previously reported including multiple dendrites, bifurcating dendrites, and up to four dendritic brushes. We propose that “dendritic brush cells” (DBCs) may be a more apt nomenclature. In Tbr2 cKO cerebellum, mature UBCs were completely absent. Migration of UBC precursors from rhombic lip to cerebellar cortex and other nuclei was impaired in Tbr2 cKO mice. Our results indicate that UBC migration and differentiation are sensitive to Tbr2 deficiency. To investigate whether UBCs develop similarly in humans as in rodents, we studied Tbr2 expression in mid-gestational human cerebellum. Remarkably, Tbr2(+) UBC precursors migrate along the same pathways in humans as in rodent cerebellum and disperse to create the same “fountain-like” appearance characteristic of UBCs exiting the rhombic lip.
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spelling pubmed-78207532021-01-23 Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration McDonough, Ashley Elsen, Gina E. Daza, Ray M. Bachleda, Amelia R. Pizzo, Donald DelleTorri, Olivia M. Hevner, Robert F. Front Neurosci Neuroscience Previous studies demonstrated specific expression of transcription factor Tbr2 in unipolar brush cells (UBCs) of the cerebellum during development and adulthood. To further study UBCs and the role of Tbr2 in their development we examined UBC morphology in transgenic mouse lines (reporter and lineage tracer) and also examined the effects of Tbr2 deficiency in Tbr2 (MGI: Eomes) conditional knock-out (cKO) mice. In Tbr2 reporter and lineage tracer cerebellum, UBCs exhibited more complex morphologies than previously reported including multiple dendrites, bifurcating dendrites, and up to four dendritic brushes. We propose that “dendritic brush cells” (DBCs) may be a more apt nomenclature. In Tbr2 cKO cerebellum, mature UBCs were completely absent. Migration of UBC precursors from rhombic lip to cerebellar cortex and other nuclei was impaired in Tbr2 cKO mice. Our results indicate that UBC migration and differentiation are sensitive to Tbr2 deficiency. To investigate whether UBCs develop similarly in humans as in rodents, we studied Tbr2 expression in mid-gestational human cerebellum. Remarkably, Tbr2(+) UBC precursors migrate along the same pathways in humans as in rodent cerebellum and disperse to create the same “fountain-like” appearance characteristic of UBCs exiting the rhombic lip. Frontiers Media S.A. 2021-01-08 /pmc/articles/PMC7820753/ /pubmed/33488348 http://dx.doi.org/10.3389/fnins.2020.598548 Text en Copyright © 2021 McDonough, Elsen, Daza, Bachleda, Pizzo, DelleTorri and Hevner. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
McDonough, Ashley
Elsen, Gina E.
Daza, Ray M.
Bachleda, Amelia R.
Pizzo, Donald
DelleTorri, Olivia M.
Hevner, Robert F.
Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration
title Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration
title_full Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration
title_fullStr Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration
title_full_unstemmed Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration
title_short Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration
title_sort unipolar (dendritic) brush cells are morphologically complex and require tbr2 for differentiation and migration
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820753/
https://www.ncbi.nlm.nih.gov/pubmed/33488348
http://dx.doi.org/10.3389/fnins.2020.598548
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