Abstract
Formation of the nervous system requires a complex series of events including proper extension and guidance of neuronal axons and dendrites. Here we investigate the requirement for integrins, a class of transmembrane cell adhesion receptors, in regulating these processes across classes of C. elegans motor neurons. We show α integrin/ina-1 is expressed by both GABAergic and cholinergic motor neurons. Despite this, our analysis of hypomorphic ina-1(gm144) mutants indicates preferential involvement of α integrin/ina-1 in GABAergic commissural development, without obvious involvement in cholinergic commissural development. The defects in GABAergic commissures of ina-1(gm144) mutants included both premature termination and guidance errors and were reversed by expression of wild type ina-1 under control of the native ina-1 promoter. Our results also show that α integrin/ina-1 is important for proper outgrowth and guidance of commissures from both embryonic and post-embryonic born GABAergic motor neurons, indicating an ongoing requirement for integrin through two phases of GABAergic neuron development. Our findings provide insights into neuron-specific roles for integrin that would not be predicted based solely upon expression analysis.
Highlights
Assembling neuronal networks requires orchestration of neuronal outgrowth in a spatially and temporally controlled manner
We observed a significant increase in the percentage of incomplete GABAergic commissures in ina-1(gm144) animals compared with wild type (Figure 1C), suggesting α integrin/ina-1 is important for GABAergic commissural patterning, as previously reported [28,29,30,31]
Our findings indicate that the integrin signaling functions impacted by the ina-1(gm144) mutation are more centrally involved in GABAergic commissural patterning, compared with cholinergic, suggesting a neuron class-specific role for integrin in commissural guidance
Summary
Assembling neuronal networks requires orchestration of neuronal outgrowth in a spatially and temporally controlled manner. While a complete loss of integrin signaling causes early embryonic lethality [26,27], we have taken advantage of a hypomorphic mutation in α integrin/ina-1 (ina-1(gm144)) [28,29] to more closely examine the role of α integrin/ina-1 in the neurite patterning of specific neuron classes in vivo, using the development of commissural neurites of C. elegans motor neurons as a model. Using cell-specific expression of fluorescent reporters, we can label informative subsets of motor neurons, including their neurites, to investigate the involvement of integrins in their development. We show that decreased function of ina-1 disrupts GABAergic (D) motor neuron commissural outgrowth and guidance, consistent with previous studies [28,29,30,31]. Our findings reveal a neuron class-specific role for integrins in establishing motor neuron connectivity during development
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