Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord

Journal of Cellular and Molecular Medicine

Gabriel Rusanescu¹ 

[1] MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Charlestown, MA, USA

关键词: Notch;    chronic pain;    spinal cord;    stem cells;    neuronal differentiation;    neuronal progenitors;    adult neurogenesis;    calretinin;    nociception;    Notch3;   

DOI  :  10.1111/jcmm.12362

来源: Wiley

【 摘 要 】

Abstract

Notch receptors are key regulators of nervous system development and promoters of neural stem cells renewal and proliferation. Defects in the expression of Notch genes result in severe, often lethal developmental abnormalities. Notch3 is generally thought to have a similar proliferative, anti-differentiation and gliogenic role to Notch1. However, in some cases, Notch3 has an opposite, pro-differentiation effect. Here, we show that Notch3 segregates from Notch1 and is transiently expressed in adult rat and mouse spinal cord neuron precursors and immature neurons. This suggests that during the differentiation of adult neural progenitor cells, Notch signalling may follow a modified version of the classical lateral inhibition model, involving the segregation of individual Notch receptors. Notch3 knockout mice, otherwise neurologically normal, are characterized by a reduced number of mature inhibitory interneurons and an increased number of highly excitable immature neurons in spinal cord laminae I–II. As a result, these mice have permanently lower nociceptive thresholds, similar to chronic pain. These results suggest that defective neuronal differentiation, for example as a result of reduced Notch3 expression or activation, may underlie human cases of intractable chronic pain, such as fibromyalgia and neuropathic pain.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.