Specification of Individual Adult Motor Neuron Morphologies by Combinatorial Transcription Factor Codes

•Seven leg MNs from the same neuroblast express different combinations of six TFs•Changing the TF code results in predictable changes in MN morphology•One TF, Pb, is required for the precise morphological identities of three MNs•When these MNs are mutant for pb, flies exhibit a highly specific walking defect

SummaryHow the highly stereotyped morphologies of individual neurons are genetically specified is not well understood. We identify six transcription factors (TFs) expressed in a combinatorial manner in seven post-mitotic adult leg motor neurons (MNs) that are derived from a single neuroblast in Drosophila. Unlike TFs expressed in mitotically active neuroblasts, these TFs do not regulate each other’s expression. Removing the activity of a single TF resulted in specific morphological defects, including muscle targeting and dendritic arborization, and in a highly specific walking defect in adult flies. In contrast, when the expression of multiple TFs was modified, nearly complete transformations in MN morphologies were generated. These results show that the morphological characteristics of a single neuron are dictated by a combinatorial code of morphology TFs (mTFs). mTFs function at a previously unidentified regulatory tier downstream of factors acting in the NB but independently of factors that act in terminally differentiated neurons.