RTK signaling and epidermis remodeling instruct dendrite regrowth after pruning in the Drosophila PNS

Abstract

Morphology and function of many neuron types must be adapted to the current developmental stage through neurite pruning and regrowth. Pruning and regrowth occur during defined temporal windows, but how these are defined is often unclear. Drosophila peripheral c4da neurons prune their larval sensory dendrites in an ecdysone-induced manner during metamorphosis. They subsequently regrow adult-specific dendrites, but how dendrite regeneration is linked to pruning is not known. We show that dendrite regrowth requires two receptor tyrosine kinases (RTKs), the insulin receptor InR and Ret, and present evidence that RTK ligands are derived from the adjacent epidermis. The Drosophila epidermis is extensively remodeled during metamorphosis through ecdysone-dependent apoptosis of larval epidermal cells and expansion of adult so-called histoblasts. We find that this occurs during a time window between dendrite pruning and regrowth, and that preventing epidermis remodeling inhibits dendrite remodeling. Furthermore, the two processes might also be evolutionarily linked. We propose that dendrite pruning and regrowth are part of a biphasic response to ecdysone, where a delayed regrowth signal is via the epidermis to ensure coordination of tissue developmental processes.