MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons
Caitlin Engelhard,
Sarah Sarsfield,
Janna Merte,
Qiang Wang,
Peng Li,
Hideyuki Beppu,
Alex L Kolodkin,
Henry M Sucov,
David D Ginty
Affiliations
Caitlin Engelhard
The Solomon H Snyder Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
Sarah Sarsfield
The Solomon H Snyder Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
Janna Merte
The Solomon H Snyder Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
Qiang Wang
The Solomon H Snyder Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
Peng Li
Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, United States
Hideyuki Beppu
Department of Clinical Laboratory and Molecular Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan
Alex L Kolodkin
The Solomon H Snyder Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
Henry M Sucov
Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, United States
David D Ginty
The Solomon H Snyder Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
Bone morphogenetic protein (BMP) signaling has emerged as an important regulator of sensory neuron development. Using a three-generation forward genetic screen in mice we have identified Megf8 as a novel modifier of BMP4 signaling in trigeminal ganglion (TG) neurons. Loss of Megf8 disrupts axon guidance in the peripheral nervous system and leads to defects in development of the limb, heart, and left-right patterning, defects that resemble those observed in Bmp4 loss-of-function mice. Bmp4 is expressed in a pattern that defines the permissive field for the peripheral projections of TG axons and mice lacking BMP signaling in sensory neurons exhibit TG axon defects that resemble those observed in Megf8−/− embryos. Furthermore, TG axon growth is robustly inhibited by BMP4 and this inhibition is dependent on Megf8. Thus, our data suggest that Megf8 is involved in mediating BMP4 signaling and guidance of developing TG axons.
