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Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex

Erythropoietin (EPO), the hypoxia-inducible hematopoietic hormone, has well-established neuroprotective/neurotrophic roles in the developing central nervous system and the therapeutic potential of EPO has been widely explored in clinical studies for the treatment of perinatal hypoxic brain lesion, a...

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Autores principales: Constanthin, Paul E., Contestabile, Alessandro, Petrenko, Volodymyr, Quairiaux, Charles, Salmon, Patrick, Hüppi, Petra S., Kiss, Jozsef Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561482/
https://www.ncbi.nlm.nih.gov/pubmed/32764029
http://dx.doi.org/10.1242/dev.190249
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author Constanthin, Paul E.
Contestabile, Alessandro
Petrenko, Volodymyr
Quairiaux, Charles
Salmon, Patrick
Hüppi, Petra S.
Kiss, Jozsef Z.
author_facet Constanthin, Paul E.
Contestabile, Alessandro
Petrenko, Volodymyr
Quairiaux, Charles
Salmon, Patrick
Hüppi, Petra S.
Kiss, Jozsef Z.
author_sort Constanthin, Paul E.
collection PubMed
description Erythropoietin (EPO), the hypoxia-inducible hematopoietic hormone, has well-established neuroprotective/neurotrophic roles in the developing central nervous system and the therapeutic potential of EPO has been widely explored in clinical studies for the treatment of perinatal hypoxic brain lesion, as well as prematurity. Here, we reveal that both EPO and Epo receptor (EPOR) are expressed in the developing rat somatosensory cortex during radial migration and laminar positioning of granular and supragranular neurons. Experimental deregulation of EPO signaling using genetic approaches results in aberrant migration, as well as permanent neuronal misplacement leading to abnormal network activity and protracted sensory behavioral deficits. We identify ERK as the downstream effector of the EPO signaling pathway for neuronal migration. These findings reveal a crucial role for endogenous EPO signaling in neuronal migration, and offer important insights for understanding how the temporary deregulation of EPO could result in migration defects that lead to abnormal behavior in the adult.
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spelling pubmed-75614822020-10-20 Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex Constanthin, Paul E. Contestabile, Alessandro Petrenko, Volodymyr Quairiaux, Charles Salmon, Patrick Hüppi, Petra S. Kiss, Jozsef Z. Development Research Article Erythropoietin (EPO), the hypoxia-inducible hematopoietic hormone, has well-established neuroprotective/neurotrophic roles in the developing central nervous system and the therapeutic potential of EPO has been widely explored in clinical studies for the treatment of perinatal hypoxic brain lesion, as well as prematurity. Here, we reveal that both EPO and Epo receptor (EPOR) are expressed in the developing rat somatosensory cortex during radial migration and laminar positioning of granular and supragranular neurons. Experimental deregulation of EPO signaling using genetic approaches results in aberrant migration, as well as permanent neuronal misplacement leading to abnormal network activity and protracted sensory behavioral deficits. We identify ERK as the downstream effector of the EPO signaling pathway for neuronal migration. These findings reveal a crucial role for endogenous EPO signaling in neuronal migration, and offer important insights for understanding how the temporary deregulation of EPO could result in migration defects that lead to abnormal behavior in the adult. The Company of Biologists Ltd 2020-10-07 /pmc/articles/PMC7561482/ /pubmed/32764029 http://dx.doi.org/10.1242/dev.190249 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Constanthin, Paul E.
Contestabile, Alessandro
Petrenko, Volodymyr
Quairiaux, Charles
Salmon, Patrick
Hüppi, Petra S.
Kiss, Jozsef Z.
Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex
title Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex
title_full Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex
title_fullStr Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex
title_full_unstemmed Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex
title_short Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex
title_sort endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561482/
https://www.ncbi.nlm.nih.gov/pubmed/32764029
http://dx.doi.org/10.1242/dev.190249
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