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

Department of Experimental Medicine, Section of Human Physiology, University of Genova, Italy.
Neurobiology of Disease (Impact Factor: 5.08). 04/2011; 42(1):73-84. DOI: 10.1016/j.nbd.2011.01.006
Source: PubMed


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.

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Available from: Veronica La Padula, May 02, 2015
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    • "PNs are characterized by abnormal signaling in the affected nerves [9], which manifests as a variety of symptoms that differ depending on the type of nerve that is damaged. Symptoms can include pain, tingling or numbness in sensory PNs [10], impaired motor ability in motor PNs [11], and autonomic dysfunction in PNs of visceral nerves [12]. Few treatments are available to help alleviate symptoms and there are no cures [2]. "
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    • "They are implicated in various aspects of neural development, including neuronal differentiation (Dubois et al., 1998; Pozzoli et al., 2001), migration (Garcia-Dominguez et al., 2003; Garel et al., 2000) and axon fasciculation and guidance (Garel et al., 1997, 1999, 2002; Malgaretti et al., 1997; Prasad et al., 1998; Wang et al., 1997). One member of this family , Ebf2, plays an important role in neuroendocrine, olfactory, skeletal and peripheral nerve development (Corradi et al., 2003; Giacomini et al., 2011; Kieslinger et al., 2005; Wang et al., 2004). In cerebellum, Ebf2 is involved in patterning of the cortex (Chung et al., 2008; Croci et al., 2006) and Purkinje cell survival (Croci et al., 2011). "
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