Cell lineage predicts neural connectivity beyond cell type

Abstract

During nervous system development, repeated cell divisions of the zygote give rise to a "family tree" of neurons related by mitotic lineage. The developmental process also gives rise to neuronal connections, and neurons phenotypically converge to different cell types. Neural connections are steered by cell type, but they may be driven in part by lineage: We do not know if lineage matters for the developmental neurogenesis process. We thus asked if mitotic lineage predicts neural connections beyond cell type alone. Using three C. elegans datasets, we fit models for edge prediction tasks: predicting synaptic targets, and predicting synaptic sources. Adding the mitotic lineage improved these predictions. Our results suggest that the family tree matters for the connections made by neurons, and that developmental lineage is a variable that should be considered more deeply in models of connectome assembly.