Runx1 contributes to the functional switching of bone morphogenetic protein 4 (BMP4) from neurite outgrowth promoting to suppressing in dorsal root ganglion

摘要

The runt-related transcription factor Runxl regulates cell-type specification and axonal projections of nociceptive dorsal root ganglion (DRG) neurons, whereas bone morphogenetic protein 4 (BMP4) is required for axonal growth during neuronal development. Although Runxl has been shown to be involved in BMP4 signaling in non-neural tissues, the Runxl function in BMP4-dependent regulation of neuronal development is unclear. To investigate interactions between Runxl and BMP4 in neurite outgrowth, we cultured DRGs from wild-type and Runxl-deficient mouse embryos in the presence or absence of BMP4. Neurite outgrowth was decreased in BMP4-treated wild-type DRGs and untreated Runxl-deficient DRGs, suggesting the inhibitory effect of BMP4 and facilitatory effect of Runxl on neurite outgrowth. In addition, the combination of BMP4 treatment and Runxl deficiency increased neurite outgrowth, suggesting that Runxl is required for BMP4-induced suppression of neurite outgrowth and that the loss of Runxl results in a functional switch of BMP4 from neurite growth suppressing to neurite growth promoting. Both BMP4 treatment and Runxl deficiency increased calcitonin gene-related peptide (CGRP)-positive neurons, and CGRP expression was not increased by BMP4 treatment in Runxl-deficient mice, suggesting that Runxl contributes to BMP4-induced CGRP expression in DRG neurons. Thus, Runxl contributes to BMP4 regulation of neurite outgrowth and CGRP expression in DRG and may control BMP4 functional switching during embryogenesis. (C) 2016 Elsevier Inc. All rights reserved.