Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice

Caterina Giacomini, Veronica La Padula, Angelo Schenone, Massimo Leandri, Andrea Contestabile, Diego Moruzzo, Laurence Goutebroze, G. Giacomo Consalez, Fabio Benfenati, Anna Corradi

Research output: Contribution to journalArticle

Abstract

Charcot-Marie-Tooth neuropathies are frequent hereditary disorders of the nervous system and most cases remain without a molecular definition. Mutations in transcription factors have been previously associated to various types of this disease. Mice carrying a null mutation in Ebf2 transcription factor present peripheral nerve abnormalities. To get insight into Ebf2 function in peripheral nervous system, here we characterize the peripheral neuropathy affecting these mice. We first show that Ebf2 is largely expressed in peripheral nerve throughout postnatal development, its expression being not only restricted to non-myelin forming Schwann cells, but also involving myelin forming Schwann cells and the perineurium. As a consequence, the onset of myelination is delayed and Schwann cell differentiation markers are downregulated in Ebf2-/- mice. Later in development, myelin pathology appears less severe and characterized by isolated clusters of hypomyelinated fibers. However, we find defects in the nerve architecture, such as abnormalities of the nodal region and shorter internodal length. Furthermore, we demonstrate a significant decrease in axonal calibre, with a lack of large calibre axons, and a severe impairment of motor nerve conduction velocity and amplitude, whereas the sensory nerve parameters are less affected. Interestingly, a clinical case with peripheral motor neuropathy and clinical features similar to Ebf2-/- mice phenotype was associated with a deletion encompassing EBF2 human genomic locus. These findings demonstrate that Ebf2 is a new molecule implicated in peripheral nerve development and a potential candidate gene for peripheral nerve disorders.

Original languageEnglish
Pages (from-to)73-84
Number of pages12
JournalNeurobiology of Disease
Volume42
Issue number1
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Schwann Cells
Peripheral Nervous System Diseases
Peripheral Nerves
Myelin Sheath
Transcription Factors
Charcot-Marie-Tooth Disease
Mutation
Neural Conduction
Differentiation Antigens
Peripheral Nervous System
Nervous System Diseases
Axons
Cell Differentiation
Down-Regulation
Pathology
Phenotype
Genes

Keywords

  • Ebf2-/- mice
  • Motor conduction velocity
  • Myelin
  • Peripheral neuropathy
  • Transcription factor

ASJC Scopus subject areas

  • Neurology

Cite this

Giacomini, C., La Padula, V., Schenone, A., Leandri, M., Contestabile, A., Moruzzo, D., ... Corradi, A. (2011). Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice. Neurobiology of Disease, 42(1), 73-84. https://doi.org/10.1016/j.nbd.2011.01.006

Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice. / Giacomini, Caterina; La Padula, Veronica; Schenone, Angelo; Leandri, Massimo; Contestabile, Andrea; Moruzzo, Diego; Goutebroze, Laurence; Consalez, G. Giacomo; Benfenati, Fabio; Corradi, Anna.

In: Neurobiology of Disease, Vol. 42, No. 1, 04.2011, p. 73-84.

Research output: Contribution to journalArticle

Giacomini, C, La Padula, V, Schenone, A, Leandri, M, Contestabile, A, Moruzzo, D, Goutebroze, L, Consalez, GG, Benfenati, F & Corradi, A 2011, 'Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice', Neurobiology of Disease, vol. 42, no. 1, pp. 73-84. https://doi.org/10.1016/j.nbd.2011.01.006
Giacomini C, La Padula V, Schenone A, Leandri M, Contestabile A, Moruzzo D et al. Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice. Neurobiology of Disease. 2011 Apr;42(1):73-84. https://doi.org/10.1016/j.nbd.2011.01.006
Giacomini, Caterina ; La Padula, Veronica ; Schenone, Angelo ; Leandri, Massimo ; Contestabile, Andrea ; Moruzzo, Diego ; Goutebroze, Laurence ; Consalez, G. Giacomo ; Benfenati, Fabio ; Corradi, Anna. / Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice. In: Neurobiology of Disease. 2011 ; Vol. 42, No. 1. pp. 73-84.
@article{1e0c79c2739c41859e90852a4511bd5b,
title = "Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice",
abstract = "Charcot-Marie-Tooth neuropathies are frequent hereditary disorders of the nervous system and most cases remain without a molecular definition. Mutations in transcription factors have been previously associated to various types of this disease. Mice carrying a null mutation in Ebf2 transcription factor present peripheral nerve abnormalities. To get insight into Ebf2 function in peripheral nervous system, here we characterize the peripheral neuropathy affecting these mice. We first show that Ebf2 is largely expressed in peripheral nerve throughout postnatal development, its expression being not only restricted to non-myelin forming Schwann cells, but also involving myelin forming Schwann cells and the perineurium. As a consequence, the onset of myelination is delayed and Schwann cell differentiation markers are downregulated in Ebf2-/- mice. Later in development, myelin pathology appears less severe and characterized by isolated clusters of hypomyelinated fibers. However, we find defects in the nerve architecture, such as abnormalities of the nodal region and shorter internodal length. Furthermore, we demonstrate a significant decrease in axonal calibre, with a lack of large calibre axons, and a severe impairment of motor nerve conduction velocity and amplitude, whereas the sensory nerve parameters are less affected. Interestingly, a clinical case with peripheral motor neuropathy and clinical features similar to Ebf2-/- mice phenotype was associated with a deletion encompassing EBF2 human genomic locus. These findings demonstrate that Ebf2 is a new molecule implicated in peripheral nerve development and a potential candidate gene for peripheral nerve disorders.",
keywords = "Ebf2-/- mice, Motor conduction velocity, Myelin, Peripheral neuropathy, Transcription factor",
author = "Caterina Giacomini and {La Padula}, Veronica and Angelo Schenone and Massimo Leandri and Andrea Contestabile and Diego Moruzzo and Laurence Goutebroze and Consalez, {G. Giacomo} and Fabio Benfenati and Anna Corradi",
year = "2011",
month = "4",
doi = "10.1016/j.nbd.2011.01.006",
language = "English",
volume = "42",
pages = "73--84",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice

AU - Giacomini, Caterina

AU - La Padula, Veronica

AU - Schenone, Angelo

AU - Leandri, Massimo

AU - Contestabile, Andrea

AU - Moruzzo, Diego

AU - Goutebroze, Laurence

AU - Consalez, G. Giacomo

AU - Benfenati, Fabio

AU - Corradi, Anna

PY - 2011/4

Y1 - 2011/4

N2 - Charcot-Marie-Tooth neuropathies are frequent hereditary disorders of the nervous system and most cases remain without a molecular definition. Mutations in transcription factors have been previously associated to various types of this disease. Mice carrying a null mutation in Ebf2 transcription factor present peripheral nerve abnormalities. To get insight into Ebf2 function in peripheral nervous system, here we characterize the peripheral neuropathy affecting these mice. We first show that Ebf2 is largely expressed in peripheral nerve throughout postnatal development, its expression being not only restricted to non-myelin forming Schwann cells, but also involving myelin forming Schwann cells and the perineurium. As a consequence, the onset of myelination is delayed and Schwann cell differentiation markers are downregulated in Ebf2-/- mice. Later in development, myelin pathology appears less severe and characterized by isolated clusters of hypomyelinated fibers. However, we find defects in the nerve architecture, such as abnormalities of the nodal region and shorter internodal length. Furthermore, we demonstrate a significant decrease in axonal calibre, with a lack of large calibre axons, and a severe impairment of motor nerve conduction velocity and amplitude, whereas the sensory nerve parameters are less affected. Interestingly, a clinical case with peripheral motor neuropathy and clinical features similar to Ebf2-/- mice phenotype was associated with a deletion encompassing EBF2 human genomic locus. These findings demonstrate that Ebf2 is a new molecule implicated in peripheral nerve development and a potential candidate gene for peripheral nerve disorders.

AB - Charcot-Marie-Tooth neuropathies are frequent hereditary disorders of the nervous system and most cases remain without a molecular definition. Mutations in transcription factors have been previously associated to various types of this disease. Mice carrying a null mutation in Ebf2 transcription factor present peripheral nerve abnormalities. To get insight into Ebf2 function in peripheral nervous system, here we characterize the peripheral neuropathy affecting these mice. We first show that Ebf2 is largely expressed in peripheral nerve throughout postnatal development, its expression being not only restricted to non-myelin forming Schwann cells, but also involving myelin forming Schwann cells and the perineurium. As a consequence, the onset of myelination is delayed and Schwann cell differentiation markers are downregulated in Ebf2-/- mice. Later in development, myelin pathology appears less severe and characterized by isolated clusters of hypomyelinated fibers. However, we find defects in the nerve architecture, such as abnormalities of the nodal region and shorter internodal length. Furthermore, we demonstrate a significant decrease in axonal calibre, with a lack of large calibre axons, and a severe impairment of motor nerve conduction velocity and amplitude, whereas the sensory nerve parameters are less affected. Interestingly, a clinical case with peripheral motor neuropathy and clinical features similar to Ebf2-/- mice phenotype was associated with a deletion encompassing EBF2 human genomic locus. These findings demonstrate that Ebf2 is a new molecule implicated in peripheral nerve development and a potential candidate gene for peripheral nerve disorders.

KW - Ebf2-/- mice

KW - Motor conduction velocity

KW - Myelin

KW - Peripheral neuropathy

KW - Transcription factor

UR - http://www.scopus.com/inward/record.url?scp=79751524086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79751524086&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2011.01.006

DO - 10.1016/j.nbd.2011.01.006

M3 - Article

C2 - 21220016

AN - SCOPUS:79751524086

VL - 42

SP - 73

EP - 84

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 1

ER -