Cell lineage predicts neural connectivity beyond cell type

Abstract

As an organism develops, a zygote becomes the body through repeated cell division. This process produces the mitotic family tree, and cells specialize into their ultimate phenotype through interaction with other cells but also through the history of divisions. Biologists often cluster cells in the body into “cell types,” using e.g. their morphologies and molecular makeup. While morphomolecular cell type carries information about phenotype and function, there may be unknown, missing information available in this family tree. Emerging methods are making these lineage trees progressively observable. Here, using the complete mitotic family tree and connectome of the nematodeC. eleganswe ask about the role of cell-types and their family tree. We can thus evaluate how well we can predict synaptic connection with only cell-type information versus with the family tree lineage. We show that neglecting lineage can produce misleading insights into the mechanisms underlying neural wiring: underlying lineage can confound the effect of cell type. These results suggest that the concept of cell-type needs to be re-thought in the context of this emerging knowledge about cell lineage.