Abstract
Disruption of the Frizzled3 (Fz3) gene leads to defects in axonal growth in the VII(th) and XII(th) cranial motor nerves, the phrenic nerve, and the dorsal motor nerve in fore- and hindlimbs. In Fz3(-/-) limbs, dorsal axons stall at a precise location in the nerve plexus, and, in contrast to the phenotypes of several other axon path-finding mutants, Fz3(-/-) dorsal axons do not reroute to other trajectories. Affected motor neurons undergo cell death 2 days prior to the normal wave of developmental cell death that coincides with innervation of muscle targets, providing in vivo evidence for the idea that developing neurons with long-range axons are programmed to die unless their axons arrive at intermediate targets on schedule. These experiments implicate planar cell polarity (PCP) signaling in motor axon growth and they highlight the question of how PCP proteins, which form cell-cell complexes in epithelia, function in the dynamic context of axonal growth. DOI: http://dx.doi.org/10.7554/eLife.01482.001.
Highlights
The vertebrate nervous system is highly evolved to extract, integrate, retrieve, and transform information, a functional sophistication that is mirrored in the complexity of its underlying neural circuits
Fz3 is widely expressed in the developing mouse central nervous system (CNS), and it seemed possible that its loss might impair neurodevelopmental processes other than those previously described in the forebrain (Wang et al, 2002, 2006b)
Flatmounts of E18.5 Hb9-EGFP;Fz3−/− diaphragms co-stained for GFP and nicotinic acetylcholine receptors showed variability in phrenic nerve thickness within the diaphragm that correlated with nerve branching defects, and a decrease in the number of neuromuscular junctions (Figure 1D–H′′)
Summary
The vertebrate nervous system is highly evolved to extract, integrate, retrieve, and transform information, a functional sophistication that is mirrored in the complexity of its underlying neural circuits. These circuits are produced by precisely orchestrated patterns of neuronal proliferation, migration, and differentiation, and by the establishment of specific synaptic connections between neurons and their targets. Spinal motor neurons in the lateral motor column (LMC) innervate the limbs and are present only at brachial and lumbar levels. The LMC is divided into lateral (LMCL) and medial (LMCM) divisions, which innervate, respectively, the dorsal and ventral limb musculature
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