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Publication : Netrin-1 receptor DCC is required for the contralateral topography of lamina I anterolateral system neurons.

First Author  Bourojeni FB Year  2021
Journal  Pain Volume  162
Issue  1 Pages  161-175
PubMed ID  32701653 Mgi Jnum  J:317467
Mgi Id  MGI:6856466 Doi  10.1097/j.pain.0000000000002012
Citation  Bourojeni FB, et al. (2021) Netrin-1 receptor DCC is required for the contralateral topography of lamina I anterolateral system neurons. Pain 162(1):161-175
abstractText  Anterolateral system (AS) neurons relay nociceptive information from the spinal cord to the brain, protecting the body from harm by evoking a variety of behaviours and autonomic responses. The developmental programs that guide the connectivity of AS neurons remain poorly understood. Spinofugal axons cross the spinal midline in response to Netrin-1 signalling through its receptor deleted in colorectal carcinoma (DCC); however, the relevance of this canonical pathway to AS neuron development has only been demonstrated recently. Here, we disrupted Netrin-1:DCC signalling developmentally in AS neurons and assessed the consequences on the path finding of the different classes of spinofugal neurons. Many lamina I AS neurons normally innervate the lateral parabrachial nucleus and periaqueductal gray on the contralateral side. The loss of DCC in the developing spinal cord resulted in increased frequency of ipsilateral projection of spinoparabrachial and spinoperiaqueductal gray neurons. Given that contralateral spinofugal projections are largely associated with somatotopic representation of the body, changes in the laterality of AS spinofugal projections may contribute to reduced precision in pain localization observed in mice and humans carrying Dcc mutations.
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