| First Author | Dumoulin A | Year | 2024 |
| Journal | Development | Volume | 151 |
| Issue | 17 | PubMed ID | 39157903 |
| Mgi Jnum | J:354197 | Mgi Id | MGI:7733226 |
| Doi | 10.1242/dev.202788 | Citation | Dumoulin A, et al. (2024) A cell-autonomous role for primary cilium-mediated signaling in long-range commissural axon guidance. Development 151(17) |
| abstractText | Ciliopathies are characterized by the absence or dysfunction of primary cilia. Despite the fact that cognitive impairments are a common feature of ciliopathies, how cilia dysfunction affects neuronal development has not been characterized in detail. Here, we show that primary cilium-mediated signaling is required cell-autonomously by neurons during neural circuit formation. In particular, a functional primary cilium is crucial during axonal pathfinding for the switch in responsiveness of axons at a choice point or intermediate target. Using different animal models and in vivo, ex vivo and in vitro experiments, we provide evidence for a crucial role of primary cilium-mediated signaling in long-range axon guidance. The primary cilium on the cell body of commissural neurons transduces long-range guidance signals sensed by growth cones navigating an intermediate target. In extension of our finding that Shh is required for the rostral turn of post-crossing commissural axons, we suggest a model implicating the primary cilium in Shh signaling upstream of a transcriptional change of axon guidance receptors, which in turn mediate the repulsive response to floorplate-derived Shh shown by post-crossing commissural axons. |
