Hormonal control of postmitotic neuronal identity

Developmental transcriptional programs establish neuronal diversity and circuit assembly, but how these regulators continue to shape and preserve neuronal identity remains unresolved. The <i>Drosophila</i> central complex comprises precisely wired circuits of diverse neuronal types that coordinate complex behaviors. Within this structure, dorsal fan-shaped body (dFB) neurons integrate internal-state signals to regulate sleep, feeding, and energy homeostasis, yet how distinct dFB subtypes are specified and maintained remains unknown. More broadly, whether developmental transcription factors continue to act in mature neurons to preserve neuronal identity is poorly understood. Here, we define the developmental origin and molecular regulation of neuronal identity in 84C10-labelled dFB neurons that innervate layers 6-7 of the FB and contribute to nutrient sensing and metabolic adaptation. Using lineage tracing, clonal analysis, and birth dating, we show that dFB neurons are generated late in development and arise from two distinct type II neural stem cell lineages, dorsolateral 1 and dorsomedial 4. These dFB neurons continue to express the late temporal transcription factor, ecdysone-induced protein 93 (E93), in adulthood. Post-mitotic depletion of E93 results in progressive neuronal loss and ectopic expansion of axonal arborizations across FB layers and, notably, a marked reduction in vesicular glutamate transporter (vGLUT) expression. These defects are accompanied by impaired increases in fat-to-lean mass ratios in response to high-sugar feeding. Together, our findings identify E93 as a post-mitotically retained temporal transcription factor that maintains neuronal survival, laminar connectivity, and neurotransmitter identity, revealing that developmental temporal programs are redeployed in adulthood to sustain neuronal identity and function.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-01-29
DOI
https://doi.org/10.64898/2026.01.28.702037
Primary Topic
Neurobiology and Insect Physiology Research
Type
article
Field-Weighted Citation Impact
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article

Hormonal control of postmitotic neuronal identity

Mubarak Hussain Syed, Adil Rashid Wani, Riley K.R. Woerner, Rahail Ashraf et al.
bioRxiv (Cold Spring Harbor Laboratory)
Neurobiology and Insect Physiology Research
article

Hormonal control of postmitotic neuronal identity

Mubarak Hussain Syed, Adil Rashid Wani, Riley K.R. Woerner, Rahail Ashraf, Monica Dus, Qussin Basharat Joo
article en

Abstract

Developmental transcriptional programs establish neuronal diversity and circuit assembly, but how these regulators continue to shape and preserve neuronal identity remains unresolved. The <i>Drosophila</i> central complex comprises precisely wired circuits of diverse neuronal types that coordinate complex behaviors. Within this structure, dorsal fan-shaped body (dFB) neurons integrate internal-state signals to regulate sleep, feeding, and energy homeostasis, yet how distinct dFB subtypes are specified and maintained remains unknown. More broadly, whether developmental transcription factors continue to act in mature neurons to preserve neuronal identity is poorly understood. Here, we define the developmental origin and molecular regulation of neuronal identity in 84C10-labelled dFB neurons that innervate layers 6-7 of the FB and contribute to nutrient sensing and metabolic adaptation. Using lineage tracing, clonal analysis, and birth dating, we show that dFB neurons are generated late in development and arise from two distinct type II neural stem cell lineages, dorsolateral 1 and dorsomedial 4. These dFB neurons continue to express the late temporal transcription factor, ecdysone-induced protein 93 (E93), in adulthood. Post-mitotic depletion of E93 results in progressive neuronal loss and ectopic expansion of axonal arborizations across FB layers and, notably, a marked reduction in vesicular glutamate transporter (vGLUT) expression. These defects are accompanied by impaired increases in fat-to-lean mass ratios in response to high-sugar feeding. Together, our findings identify E93 as a post-mitotically retained temporal transcription factor that maintains neuronal survival, laminar connectivity, and neurotransmitter identity, revealing that developmental temporal programs are redeployed in adulthood to sustain neuronal identity and function.

bioRxiv (Cold Spring Harbor Laboratory)
University of New Mexico (US), University of Michigan (US)
National Science Foundation, Brain and Behavior Research Foundation, McKnight Foundation
Openalex Percentile: Top 75%
Neurobiology and Insect Physiology Research
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