Ephrin-A2 and ephrin-A5 guide contralateral targeting but not topographic mapping of ventral cochlear nucleus axons.

BACKGROUND: In the auditory brainstem, ventral cochlear nucleus (VCN) axons project to the contralateral, but not ipsilateral, medial nucleus of trapezoid body (MNTB), terminating in the calyx of Held. Dorsal VCN neurons, representing high frequencies, synapse with medial MNTB neurons, while low frequency-coding ventral VCN neurons synapse with lateral MNTB neurons, reflecting tonotopic organization. The mechanisms that ensure strictly contralateral targeting and topographic ordering are incompletely understood. Here we examined the roles of ephrin-A signaling in both types of targeting. RESULTS: Ephrin-A2 and ephrin-A5 are expressed in VCN cells during late embryonic and early postnatal development. At these ages ephrin-A2 is expressed in axons surrounding MNTB and ephrin-A5 is expressed in MNTB principal neurons. Ephrin-A2/A5 double knockout mice displayed axon targeting errors in which VCN axons project to MNTB on both sides of the brainstem, where they terminate in calyceal endings. Ephrin-A2 and ephrin-A5 single knockout mice showed a similar phenotype. In contrast to effects on contralateral targeting, ephrin-A2/A5 double knockout mice showed no defects in formation of tonotopically ordered projections from VCN to MNTB. CONCLUSIONS: These findings demonstrate that distinct mechanisms regulate targeting of VCN axons to the contralateral MNTB and targeting to appropriate tonotopic locations. Ephrin-A signaling plays a similar role to ephrin-B signaling in the VCN-MNTB pathway, where both classes normally prevent formation of calyceal projections to ipsilateral MNTB. These classes may rely in part on common signaling pathways.

Inter-cellular forces orchestrate contact inhibition of locomotion.

Contact inhibition of locomotion (CIL) is a multifaceted process that causes many cell types to repel each other upon collision. During development, this seemingly uncoordinated reaction is a critical driver of cellular dispersion within embryonic tissues. Here, we show that Drosophila hemocytes require a precisely orchestrated CIL response for their developmental dispersal. Hemocyte collision and subsequent repulsion involves a stereotyped sequence of kinematic stages that are modulated by global changes in cytoskeletal dynamics. Tracking actin retrograde flow within hemocytes in vivo reveals synchronous reorganization of colliding actin networks through engagement of an inter-cellular adhesion. This inter-cellular actin-clutch leads to a subsequent build-up in lamellar tension, triggering the development of a transient stress fiber, which orchestrates cellular repulsion. Our findings reveal that the physical coupling of the flowing actin networks during CIL acts as a mechanotransducer, allowing cells to haptically sense each other and coordinate their behaviors.