Intra-axonal Translation of SMAD1/5/8 Mediates Retrograde Regulation of Trigeminal Ganglia Subtype Specification

In many cases, neurons acquire distinct identities as their axons navigate toward target cells and encounter target-derived signaling molecules. These molecules generate retrograde signals that activate subtype-specific gene transcription. Mechanisms by which axons convert the complex milieu of signaling molecules into retrograde signals are not fully understood. Here, we examine retrograde signaling mechanisms that specify neuronal identity in the trigeminal ganglia, which relays sensory information from the face to the brain. We find that neuron specification requires the sequential action of two target-derived factors, BDNF and BMP4. BDNF induces the translation of axonally localized SMAD1/5/8 transcripts. Axon-derived SMAD1/5/8 is translocated to the cell body, where it is phosphorylated to a transcriptionally active form by BMP4-induced signaling endosomes and mediates the transcriptional effects of target-derived BDNF and BMP4. Thus, local translation functions as a mechanism by which coincident signals are converted into a retrograde signal that elicits a specific transcriptional response. [Display omitted] ► BDNF and BMP4 are target derived factors for trigeminal ganglia patterning ► SMAD1/5/8 protein and mRNA are localized to trigeminal axons ► Target-derived BDNF regulates local translation of SMAD1/5/8 in axons ► Local translation of SMAD1/5/8 in axons is required for retrograde BMP4 signaling Ji and Jaffrey find that specification of neuronal identity in the trigeminal ganglia involves the sequential action of BDNF and BMP4. BDNF induces axonal translation of SMAD1/5/8. Subsequent retrograde transport to the cell body then mediates the transcriptional effects of target-derived BDNF and BMP.