The role of Celsr3 in the development of central somatosensory projections from dorsal root ganglia

Abstract Dorsal root ganglion (DRG) neurons receive peripheral somatosensory information and send orderly projections to second-order relay nuclei in the spinal cord and in the brainstem. Atypical cadherin Celsr3 is known to play a critical role in wiring of several central and peripheral axons. Although Celsr3 mRNA is heavily expressed in DRG neurons, its role in the development of somatosensory projections remains unexplored. Here we assessed the role of Celsr3 in DRG using conditional gene inactivation in crosses with Wnt1-Cre mice. Using Celsr3-GFP transgenic mice, we found that Celsr3 was highly expressed in different DRG cells, such as Pavalbumin-, TrkB-, and calcitonin gene-related peptide (CGRP)-positive neurons. Wnt1-Cre;Celsr3 f/− animals survived for a few weeks and looked smaller than littermate controls. DiI tracing showed that early DRG axons entered the spinal cord and reached spinal cord targets similarly in mutant and control mice. CGRP-positive fiber density was significantly decreased in lamina I in the mutant versus control spinal cord at postnatal day (P) 7 and P14. Furthermore, more Pavalbumin-positive fibers invaded the gray matter and made more contacts with spinal motor neurons in mutant than in control samples. Behavioral analysis showed that mutant animals were less sensitive to pain and more sensitive to mechanical stimulation than controls. In conclusion, Celsr3 is dispensable for the patterning of central DRG projections, but it regulates for the fine mapping of sensory fibers in the gray matter, which is important for somatosensory processing.