Stochastic growth and ligand-receptor interaction-mediated stabilization generate stereotyped dendritic arbors

Nat Neurosci. 2026 May 4. doi: 10.1038/s41593-026-02278-0. Online ahead of print.

ABSTRACT

Stereotyped dendritic arbors are shaped by dynamic and stochastic growth during neuronal development. It remains unclear how guidance receptors and ligands coordinate branch dynamic growth, retraction and stabilization to specify dendritic arbors. We previously showed that extracellular adhesion ligand SAX-7/LICAM dictates the elaborate and stereotyped shape of the Caenorhabditis elegans PVD sensory dendrite via binding to the guidance receptor DMA-1, a single transmembrane adhesion molecule. Here, we perform structure-function analyses of DMA-1 and unexpectedly find that robust, stochastic dendritic growth does not require ligand binding. Instead, ligand contacts prevent dendrite retraction, inhibit ectopic growth and specify arbor shape. Furthermore, we demonstrate that dendritic growth requires a pool of ligand-free DMA-1, which is maintained by receptor endocytosis and reinsertion to the plasma membrane via recycling endosomes. Mutants defective of DMA-1 endocytosis show severely truncated dendrites. We present a model in which ligand-free guidance receptor mediates intrinsic, stochastic dendritic growth, while extracellular ligands instruct dendrite shape by inhibiting growth.

PMID:42082815 | DOI:10.1038/s41593-026-02278-0