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c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor

The localization, expression, and physiological role of regulatory proteins in the neurogenic niches of the brain is fundamental to our understanding of adult neurogenesis. This study explores the expression and role of the E3-ubiquitin ligase, c-Cbl, in neurogenesis within the subventricular zone (...

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Autores principales: Vogt, Maximilian, Unnikrishnan, Madhukrishna Kolothara, Heinig, Nora, Schumann, Ulrike, Schmidt, Mirko H. H., Barth, Kathrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572332/
https://www.ncbi.nlm.nih.gov/pubmed/37830613
http://dx.doi.org/10.3390/cells12192400
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author Vogt, Maximilian
Unnikrishnan, Madhukrishna Kolothara
Heinig, Nora
Schumann, Ulrike
Schmidt, Mirko H. H.
Barth, Kathrin
author_facet Vogt, Maximilian
Unnikrishnan, Madhukrishna Kolothara
Heinig, Nora
Schumann, Ulrike
Schmidt, Mirko H. H.
Barth, Kathrin
author_sort Vogt, Maximilian
collection PubMed
description The localization, expression, and physiological role of regulatory proteins in the neurogenic niches of the brain is fundamental to our understanding of adult neurogenesis. This study explores the expression and role of the E3-ubiquitin ligase, c-Cbl, in neurogenesis within the subventricular zone (SVZ) of mice. In vitro neurosphere assays and in vivo analyses were performed in specific c-Cbl knock-out lines to unravel c-Cbl’s role in receptor tyrosine kinase signaling, including the epidermal growth factor receptor (EGFR) pathway. Our findings suggest that c-Cbl is significantly expressed within EGFR-expressing cells, playing a pivotal role in neural stem cell proliferation and differentiation. However, c-Cbl’s function extends beyond EGFR signaling, as its loss upon knock-out stimulated progenitor cell proliferation in neurosphere cultures. Yet, this effect was not detected in hippocampal progenitor cells, reflecting the lack of the EGFR in the hippocampus. In vivo, c-Cbl exerted only a minor proneurogenic influence with no measurable impact on the formation of adult-born neurons. In conclusion, c-Cbl regulates neural stem cells in the subventricular zone via the EGFR pathway but, likely, its loss is compensated by other signaling modules in vivo.
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spelling pubmed-105723322023-10-14 c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor Vogt, Maximilian Unnikrishnan, Madhukrishna Kolothara Heinig, Nora Schumann, Ulrike Schmidt, Mirko H. H. Barth, Kathrin Cells Article The localization, expression, and physiological role of regulatory proteins in the neurogenic niches of the brain is fundamental to our understanding of adult neurogenesis. This study explores the expression and role of the E3-ubiquitin ligase, c-Cbl, in neurogenesis within the subventricular zone (SVZ) of mice. In vitro neurosphere assays and in vivo analyses were performed in specific c-Cbl knock-out lines to unravel c-Cbl’s role in receptor tyrosine kinase signaling, including the epidermal growth factor receptor (EGFR) pathway. Our findings suggest that c-Cbl is significantly expressed within EGFR-expressing cells, playing a pivotal role in neural stem cell proliferation and differentiation. However, c-Cbl’s function extends beyond EGFR signaling, as its loss upon knock-out stimulated progenitor cell proliferation in neurosphere cultures. Yet, this effect was not detected in hippocampal progenitor cells, reflecting the lack of the EGFR in the hippocampus. In vivo, c-Cbl exerted only a minor proneurogenic influence with no measurable impact on the formation of adult-born neurons. In conclusion, c-Cbl regulates neural stem cells in the subventricular zone via the EGFR pathway but, likely, its loss is compensated by other signaling modules in vivo. MDPI 2023-10-03 /pmc/articles/PMC10572332/ /pubmed/37830613 http://dx.doi.org/10.3390/cells12192400 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vogt, Maximilian
Unnikrishnan, Madhukrishna Kolothara
Heinig, Nora
Schumann, Ulrike
Schmidt, Mirko H. H.
Barth, Kathrin
c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor
title c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor
title_full c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor
title_fullStr c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor
title_full_unstemmed c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor
title_short c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor
title_sort c-cbl regulates murine subventricular zone-derived neural progenitor cells in dependence of the epidermal growth factor receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572332/
https://www.ncbi.nlm.nih.gov/pubmed/37830613
http://dx.doi.org/10.3390/cells12192400
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