Doe, C. | bioRxiv Science

bioRxiv2026

Cell body clustering drives gap junction-mediated synchronous activity in command neurons

The nervous system contains densely packed cell bodies, yet the role of neuronal cell body position in circuit function is poorly understood. Here we show that four Drosophila Moonwalker Descending Neurons (MDNs), command neurons for backward locomotion, must maintain cell body contact to allow gap junction-dependent synchronous activity necessary to initiate backward walking. MDNs express the transcription factor Hunchback, which drives expression of the Lar cell adhesion molecule; Hunchback, Lar, and its ligand Dlp promote MDN cell body clustering and backward walking. When clustered, the gap junction protein Inx8 allows synchronous firing of MDNs, which is required to initiate backward walking. These findings reveal a previously unappreciated role for cell body clustering and synchronous firing in neural circuit function.

neuroscience↗

bioRxiv2024

Homeodomain protein codes specify neuronal diversity in the first ganglion of the Drosophila visual system

The brain deploys diverse neuronal subtypes to split complex inputs into parallel channels--each tuned to distinct features--enabling rich neural processing. Yet how progenitors generate distinct but functionally related subtypes remains unknown. In the Drosophila lamina (five lamina neuron subtypes receiving photoreceptor input), we uncover the regulatory logic: a pan-class homeodomain transcription factor (HDTF), induced by Hedgehog in progenitors and maintained in all lamina neurons, drives diversification within the lamina neuron class by orchestrating a four-step program across the progenitor-to-newborn neuron transition. Specifically, it establishes progenitor identity, promotes cell-cycle exit, induces subtype-specific HDTFs, and acts as their obligate cofactor to specify distinct subtypes. Loss of subtype-specific HDTFs in newborn--but not older--neurons drives subtype-to-subtype fate conversions at molecular, morphological, and functional levels, including a contrast-to-luminance encoding switch. In the mouse retina, we find that each of the 63 amacrine, 15 bipolar, and 45 retinal ganglion cell subtypes expresses pan-class and subtype-specific HDTFs, indicating evolutionary conservation of this regulatory logic. Given the brain-wide expression of HDTFs across species, these findings convert a longstanding mystery into a testable, generalizable principle for within-class subtype diversification and lay the groundwork for subtype-precise reprogramming and cell replacement strategies.

developmental biology↗