Stereotyped terminal axon branching of leg motor neurons mediated by IgSF proteins DIP-α and Dpr10

Abstract

For animals to perform coordinated movements requires the precise organization of neural circuits controlling motor function. Motor neurons (MNs), key components of these circuits, project their axons from the central nervous system and form precise terminal branching patterns at specific muscles. Focusing on the Drosophila leg neuromuscular system, we show that the stereotyped terminal branching of a subset of MNs is mediated by interacting transmembrane Ig superfamily proteins DIP-α and Dpr10, present in MNs and target muscles, respectively. The DIP-α/Dpr10 interaction is needed only after MN axons reach the vicinity of their muscle targets. Live imaging suggests that precise terminal branching patterns are gradually established by DIP-α/Dpr10-dependent interactions between fine axon filopodia and developing muscles. Further, different leg MNs depend on the DIP-α and Dpr10 interaction to varying degrees that correlate with the morphological complexity of the MNs and their muscle targets.

Transneuronal Dpr12/DIP-δ interactions facilitate compartmentalized dopaminergic innervation ofDrosophilamushroom body axons

“…Expression patterns of Dpr and DIP molecules in the neuromuscular junction (NMJ) (22) and visual system (22, 28) suggested a model where these molecules instruct target cell specificity. Recent loss-of-function experiments strengthened this target specificity hypothesis as the DIP-α- 30 Dpr10 interaction was shown to be important for motoneuron innervation of specific larval (29) and adult (30) muscles and DIP-α-Dpr10/Dpr6 interaction for specific layer targeting in the visual system (31). Our results suggest that mechanisms used to target axons and dendrites to specific cell types or layers may be further implicated to orchestrate the formation of axonal compartment.…”

“…We visualized Dpr12 and DIP-δ GFP fusion proteins in brains homozygous mutant for their reciprocal Dpr/DIP partner. 30 We found that Dpr12 expression appears diffuse in DIP-δ mutant brains throughout development ( fig. S11), indicating that Dpr12 protein localization requires interaction with DIP-δ, likely on PAM-DANs.…”

Coordination between stochastic and deterministic specification in the Drosophila visual system

“…Thus, we propose that Dprs and DIPs act during a later step of circuit formation to allow distinct neurons that project to the same layer to distinguish their appropriate synaptic partners. Analysis of other Dpr/DIP pairs in and outside the visual system support this view (Barish et al, 2018;Venkatasubramanian et al, 2019;Xu et al, 2018aXu et al, , 2018b. In the medulla, DIPα is expressed in three Dm neurons (Dm1, Dm4 and Dm12) whereas its ligands Dpr6 and Dpr10 are expressed in neurons innervating the layers occupied by these Dm neurons (Xu et al, 2018b).…”

A size principle for leg motor control inDrosophila

“…The gradients in functional properties correlate with the developmental birth order of leg motor neurons: the fast tibia flexor is born embryonically, and then more proximal-targeting neurons are born before neurons with distal axonal projections . Thus, the principles governing motor neuron development (Venkatasubramanian et al, 2019) and circuit assembly (Enriquez et al, 2015) may also determine their physiological properties.…”