Motor Neuron Position and Topographic Order Imposed by β- and γ-Catenin Activities

Department of Neuroscience, Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA.
Cell (Impact Factor: 32.24). 10/2011; 147(3):641-52. DOI: 10.1016/j.cell.2011.09.037
Source: PubMed


Neurons typically settle at positions that match the location of their synaptic targets, creating topographic maps. In the spinal cord, the organization of motor neurons into discrete clusters is linked to the location of their muscle targets, establishing a topographic map of punctate design. To define the significance of motor pool organization for neuromuscular map formation, we assessed the role of cadherin-catenin signaling in motor neuron positioning and limb muscle innervation. We find that joint inactivation of β- and γ-catenin scrambles motor neuron settling position in the spinal cord but fails to erode the predictive link between motor neuron transcriptional identity and muscle target. Inactivation of N-cadherin perturbs pool positioning in similar ways, albeit with reduced penetrance. These findings reveal that cadherin-catenin signaling directs motor pool patterning and imposes topographic order on an underlying identity-based neural map.

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    • "The identification of phrenic MN-specific cadherins is significant, as adhesion molecules of this protein family are expressed in specific combinations on many, if not all, MN subsets. Cadherins mediate like-like clustering of MN cell bodies and drive the formation of topographic maps in the ventral spinal cord (Bello et al., 2012; Demireva et al., 2011; Price et al., 2002). In summary, we were able to identify a large number of genes potentially enriched in primary phrenic neurons and confirmed most of those analysed by histology. "
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    • "The ability to disrupt normal programs of motor pool clustering and positioning through manipulation of cadherin signaling has also permitted a test of Romanes's second conjecture—that motor neuron positioning contributes to the precision and fidelity of muscle target innervation. Here, however, scrambling motor neuron position through inactivation of cadherin signaling fails to undermine the predictive link between the transcriptional identity of a motor neuron and the selection of its muscle target (Demireva et al., 2011). Presumably, profiles of expression and Figure 3. "
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    • "Alternatively, and akin to the situation in Drosophila (Zlatic et al., 2009), a motor neuron-independent program of mediolateral sensory targeting could underlie the avoidance of neurons in antagonist columels. Scrambling motor neuron position while maintaining transcriptional distinctions in divisional identity (see Demireva et al., 2011) could help to resolve these possibilities. It is also unclear how the variably weighted sensory connections with motor pools within a columel are established. "
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