Summary Background Dendrites often display remarkably complex and diverse morphologies that are influenced by developmental and environmental cues. Neuroplasticity in response to adverse environmental conditions entails both hypertrophy and resorption of dendrites. How dendrites rapidly alter morphology in response to unfavorable environmental conditions is unclear. The nematode Caenorhabditis elegans enters into a stress-resistant dauer larval stage in response to an adverse environment. Results Here we show that the IL2 bipolar sensory neurons undergo dendrite arborization and axon remodeling during dauer development. When dauer larvae are returned to favorable environmental conditions, animals resume reproductive development and IL2 dendritic branches retract, leaving behind remnant branches in post-dauer L4 and adult animals. The C. elegans furin homolog KPC-1 is required for dauer IL2 dendritic arborization and dauer specific nictation behavior. kpc-1 is also necessary for dendritic arborization of PVD and FLP sensory neurons. In mammals, furin is essential, ubiquitously expressed, and associated with numerous pathologies including neurodegenerative diseases. While broadly expressed in C. elegans neurons and epithelia, kpc-1 acts cell autonomously in IL2 neurons to regulate dauer-specific dendritic arborization and nictation. Conclusions Neuroplasticity of the C. elegans IL2 sensory neurons provides a paradigm to study stress-induced and reversible dendritic branching, and the role of environmental and developmental cues in this process. The newly discovered role of KPC-1 in dendrite morphogenesis provides insight into the function of proprotein convertases in nervous system development.

Summary Cilia and extracellular vesicles (EVs) are signaling organelles[1]. Cilia act as cellular sensory antennae, with defects resulting in human ciliopathies. Cilia both release and bind to EVs[1]. EVs are submicron-sized particles released by cells and function in both short and long range intercellular communication. In C. elegans and mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation[2]. A fundamental understanding of EV biology and the relationship between the polycystins, cilia, and EVs is lacking. To define properties of a ciliated EV-releasing cell, we performed RNAseq on 27 GFP-labeled EV releasing neurons (EVNs) isolated from adult C. elegans. We identified 335 significantly overrepresented genes, of which 61 were validated by GFP reporters. The EVN transcriptional profile uncovered new pathways controlling EV biogenesis and polycystin signaling and also identified EV cargo, which included an antimicrobial peptide and ASIC channel. Tumor necrosis associated factor (TRAF) homologues trf-1 and trf-2 and the p38 mitogen-activated protein kinase (MAPK) pmk-1 acted in polycystin signaling pathways controlling male mating behaviors. pmk-1 was also required for EV biogenesis, independent of the innate immunity MAPK signaling cascade. This first high-resolution transcriptome profile of a subtype of ciliated sensory neurons isolated from adult animals reveals the functional components of an EVN.

Phagocytosis of dying cells is critical in development and immunity1–3. While proteins for recognition and engulfment of cellular debris following cell death are known4,5, proteins that directly mediate phagosome sealing are uncharacterized. Furthermore, whether all phagocytic targets are cleared using the same machinery is unclear. Degeneration of morphologically-complex cells, such as neurons, glia, and melanocytes, produces phagocytic targets of various shapes and sizes located in different microenvironments6,7. Such cells, therefore, offer unique settings to explore engulfment program mechanisms and specificity. Here we report that dismantling and clearance of a morphologically-complex C. elegans epithelial cell requires separate cell-soma, proximal-, and distal-process programs. Similar compartment-specific events govern elimination of a C. elegans neuron. While canonical engulfment proteins drive cell-soma clearance, these are not required for process removal. We find that EFF-1, a protein previously implicated in cell-cell fusion8, specifically promotes distal-process phagocytosis. EFF-1 localizes to phagocyte pseudopod tips, and acts exoplasmically to drive phagosome sealing. eff-1 mutations result in phagocytosis arrest with unsealed phagosomes. Our studies suggest universal mechanisms for dismantling morphologically-complex cells, and uncover a phagosome sealing component promoting cell-process clearance.

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SUMMARYMotoneurons and motoneuron-like pancreatic beta cells arise from radial glia and ductal cells, both tube-lining progenitors that share molecular regulators. To uncover programs underlying motoneuron formation, we studied a similar, cell-division-independent transformation of the C. elegans tube-lining Y cell into the PDA motoneuron. We find that lin-12/Notch acts through ngn-1/Ngn and its regulator hlh-16/Olig to control transformation timing. lin-12 loss blocks transformation, while lin-12(gf) promotes precocious PDA formation. Early basal expression of both ngn-1/Ngn and hlh-16/Olig depends on sem-4/Sall and egl-5/Hox. Later, coincident with Y-cell morphological changes, ngn-1/Ngn expression is upregulated in a sem-4/Sall and egl-5/Hox-dependent but hlh-16/Olig-independent manner. Subsequently, Y-cell retrograde extension forms an anchored process priming PDA axon extension. Extension requires ngn-1-dependent expression of the cytoskeleton organizers UNC-119, UNC-44/ANK, and UNC-33/CRMP, which also, unexpectedly, activate PDA terminal-gene expression. Our findings reveal key cell-division-independent regulatory events leading to motoneuron generation, suggesting a conserved pathway for epithelial-to-motoneuron/motoneuron-like differentiation.