Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons

Abstract

Summary Precise patterning of dendritic arbors is critical for the wiring and function of neural circuits. Dendrite-extracellular matrix (ECM) adhesion ensures that the dendrites of Drosophila dendritic arborization (da) sensory neurons are properly restricted in a 2D space, and thereby facilitates contact-mediated dendritic self-avoidance and tiling. However, the mechanisms regulating dendrite-ECM adhesion in vivo are poorly understood. Here, we show that mutations in the semaphorin ligand sema-2b lead to a dramatic increase in self-crossing of dendrites due to defects in dendrite-ECM adhesion, resulting in a failure to confine dendrites to a 2D plane. Furthermore, we find that Sema-2b is secreted from the epidermis and signals through the Plexin B receptor in neighboring neurons. Importantly, we find that Sema-2b/PlexB genetically and physically interacts with TORC2 complex, Tricornered (Trc) kinase and integrins. These results reveal a novel role for semaphorins in dendrite patterning and illustrate how epidermal-derived cues regulate neural circuit assembly.

Muscle- and Skin-Derived Cues Jointly Orchestrate Patterning of Somatosensory Dendrites

“…Yet, only a few non-autonomously acting proteins have been identified, including semaphorins [4, 5], brain derived neurotrophic factors (BDNF) [6], UNC-6/Netrin [7], and the conserved MNR-1/Menorin–SAX-7/L1CAM cell adhesion complex [8, 9]. This complex acts from the skin to pattern the stereotypic dendritic arbors of PVD and FLP somatosensory neurons in Caenorhabditis elegans through the dendritic leucine rich transmembrane receptor DMA-1/LRR-TM on PVD neurons [8, 9].…”

Olfactory Sensory Neurons Control Dendritic Complexity of Mitral Cells via Notch Signaling

“…The dendrites of Drosophila dendritic arborization neurons, which are a well-characterized model system, have been recently shown to be regulated by epidermis-secreted Sema-2b protein [4] and transcriptional programs [5]. Dendrites in neurons of the cerebral cortex also involve transcriptional regulators, such as Neurog2 [6] and Notch [7,8].…”

Ret and Substrate-Derived TGF-β Maverick Regulate Space-Filling Dendrite Growth in Drosophila Sensory Neurons

“…In Drosophila C4da neurons, Ptp69D is required for normal dendritic growth and coverage (Poe et al, 2017), whereas the protocadherin flamingo and the transmembrane protein golden goal are necessary to prevent dorsal dendrite overextension (Gao et al, 2000; Hakeda and Suzuki, 2013; Matsubara et al, 2011). Moreover, the α-integrin mew , β-integrin mys (Han et al, 2012; Kim et al, 2012b), and PlexB/ Sema2b (Meltzer et al, 2016) are required for 2-dimensional growth and ECM adhesion of sensory neuron dendrites. Ret has previously been shown to interact with integrins and Rac1 in C4 da neurons to promote dendrite-ECM adhesion and, thus, a 2-dimensional growth mode (Soba et al, 2015).…”

“…Therefore, integrins are essential to ensure repulsion-mediated self-avoidance, which restricts the growth of dendrites competing for the same territory. Similarly, loss of neuronal plexB or epithelial sema2b results in dendrite-ECM adhesion and self-avoidance defects in C4da neurons (Meltzer et al, 2016). Although dendrite-ECM adhesion ensures 2-dimensional growth required for dendrite self-encounters, loss of dendrite adhesion itself does not severely affect dendritic space-filling.…”