Modular transcriptional programs separately define axon and dendrite connectivity

Abstract

Patterns of synaptic connectivity are remarkably precise and complex. Single-cell RNA sequencing has revealed a vast transcriptional diversity of neurons. Nevertheless, a clear logic underlying the transcriptional control of neuronal connectivity has yet to emerge. Here, we focused on Drosophila T4/T5 neurons, a class of closely related neuronal subtypes with different wiring patterns. Eight subtypes of T4/T5 neurons are defined by combinations of two patterns of dendritic inputs and four patterns of axonal outputs. Single-cell profiling during development revealed distinct transcriptional programs defining each dendrite and axon wiring pattern. These programs were defined by the expression of a few transcription factors and different combinations of cell surface proteins. Gain and loss of function studies provide evidence for independent control of different wiring features. We propose that modular transcriptional programs for distinct wiring features are assembled in different combinations to generate diverse patterns of neuronal connectivity.

A combinatorial code of transcription factors specifies subtypes of visual motion-sensing neurons in Drosophila

“…We found many cell-membrane proteins with T4/T5 subtype-specific expression patterns that might result from the action of the combinatorial code of transcription factors that we uncovered here. In agreement with the results of a recent publication (Kurmangaliyev et al, 2019), the vast majority of cell-membrane proteins with subtype-specific expression patterns in T4 neurons exhibited the same expression patterns and dynamics in T5 neurons. These mostly included receptors, ligands, regulators of various signalling pathways, and cell-adhesion molecules, some of which have been shown to be involved in axon guidance, dendrite patterning and/or synaptic specificity in…”

“…5A,B). A recent study reported similar results using different reagents, ruled out that this anatomical defect is caused by neuronal apoptosis, and proposed that the overexpression of grain affects T4/T5 neurons such that their axons cannot segregate to form four layers without affecting their dendrites (Kurmangaliyev et al, 2019). Alternatively, changes in T4/T5 axon projection patterns upon grain overexpression might result from an identity conversion of T4/T5a,d…”

Atypical Myosin Tunes Dendrite Arbor Subdivision

“…One way TFs control arbor morphology is by regulation of cell surface protein and cell adhesion molecules (Hattori et al, 2013;Kurmangaliyev et al, 2019;Lefebvre et al, 2015;Peng et al, 2017). For example, in mice direction-selective retinal ganglion cells, the homeobox factor Satb1 specifies arbor stratification by regulating Contactin5, which in turn supports branch-specific adhesion to interneurons for arbor stratification (Peng et al, 2017).…”

A global timing mechanism regulates cell-type specific wiring programs

“…Wiring the brain requires precise cell-type and temporally restricted expression of genes encoding cell surface proteins 2,3,12,13,35 . Our studies uncovered a strategy that plays a widespread, yet specific role, in regulating this process.…”

“…For transcriptomic analysis of developing wildtype lamina neurons, w; UAS-H2A-GFP; 9B08-Gal4/Tm6B, tb females were crossed with males from different DGRP backgrounds (wildtype, see Supplementary Table 1 for list of DGRPs used). F1 prepupae were staged as in Kurmangaliyev et al 35 Males were only included in the analysis if no significant differences in gene expression were found with female pupae of the same genotype and developmental time point. Pupae corresponding to different developmental stages (see Fig.…”