TAG-1 Multifunctionality Coordinates Neuronal Migration, Axon Guidance, and Fasciculation

• Published in: Cell reports (Cambridge) 2020-01, Vol.30 (4), p.1164-1177.e7
• Main Authors: Suter, Tracey A.C.S., Blagburn, Sara V., Fisher, Sophie E., Anderson-Keightly, Heather M., D’Elia, Kristen P., Jaworski, Alexander
• Format: Article
• Language: English
• Subjects: adhesion; Animals; axon guidance; Axon Guidance - genetics; Axon Guidance - physiology; Axons - metabolism; Cell Line; Cell Movement - genetics; Chlorocebus aethiops; Contactin 2 - genetics; Contactin 2 - metabolism; COS Cells; development; fasciculation; Fasciculation - genetics; Fasciculation - metabolism; Ganglia, Spinal - cytology; Ganglia, Spinal - metabolism; Gene Expression Regulation, Developmental - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; motor neurons; Motor Neurons - metabolism; Neurogenesis - genetics; neuronal migration; Signal Transduction - genetics; spinal cord; Spinal Cord - metabolism; TAG-1
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.12.085

Neuronal migration, axon fasciculation, and axon guidance need to be closely coordinated for neural circuit assembly. Spinal motor neurons (MNs) face unique challenges during development because their cell bodies reside within the central nervous system (CNS) and their axons project to various targets in the body periphery. The molecular mechanisms that contain MN somata within the spinal cord while allowing their axons to exit the CNS and navigate to their final destinations remain incompletely understood. We find that the MN cell surface protein TAG-1 anchors MN cell bodies in the spinal cord to prevent their emigration, mediates motor axon fasciculation during CNS exit, and guides motor axons past dorsal root ganglia. TAG-1 executes these varied functions in MN development independently of one another. Our results identify TAG-1 as a key multifunctional regulator of MN wiring that coordinates neuronal migration, axon fasciculation, and axon guidance. [Display omitted] •TAG-1 expression during motor neuron development shifts from cell bodies to axons•TAG-1 is required to anchor motor neuron cell bodies in the central nervous system•Motor axons fail to fasciculate and exhibit guidance defects in TAG-1−/− mice•TAG-1 fulfills its multiple functions independently of one another Suter et al. demonstrate that the motor neuron cell surface molecule TAG-1 confines motor neurons to the central nervous system, promotes motor axon fasciculation, and steers motor axons past inappropriate targets. This study highlights how a single cell adhesion molecule coordinates multiple steps in neuronal wiring through partially divergent mechanisms.