| First Author | Munezane H | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 13 | Pages | 4362-4376.e6 |
| PubMed ID | 31875546 | Mgi Jnum | J:296800 |
| Mgi Id | MGI:6468830 | Doi | 10.1016/j.celrep.2019.11.112 |
| Citation | Munezane H, et al. (2019) Roles of Collagen XXV and Its Putative Receptors PTPsigma/delta in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder. Cell Rep 29(13):4362-4376.e6 |
| abstractText | Intramuscular motor innervation is an essential process in neuromuscular development. Recently, mutations in COL25A1, encoding CLAC-P/collagen XXV, have been linked to the development of a congenital cranial dysinnervation disorder (CCDD). Yet the molecular mechanisms of intramuscular innervation and the etiology of CCDD related to COL25A1 have remained elusive. Here, we report that muscle-derived collagen XXV is indispensable for intramuscular innervation. In developing skeletal muscles, Col25a1 expression is tightly regulated by muscle excitation. In vitro and cell-based assays reveal a direct interaction between collagen XXV and receptor protein tyrosine phosphatases (PTPs) sigma and delta. Motor explant assays show that expression of collagen XXV in target cells attracts motor axons, but this is inhibited by exogenous PTPsigma/delta. CCDD mutations attenuate motor axon attraction by reducing collagen XXV-PTPsigma/delta interaction. Overall, our study identifies PTPsigma/delta as putative receptors for collagen XXV, implicating collagen XXV and PTPsigma/delta in intramuscular innervation and a developmental ocular motor disorder. |
