Biology subjects

Syed, M. H.

Publications and source records attributed to Syed, M. H..

7 recordsLinked to original sources

bioRxiv2026

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 Drosophila 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.

neuroscience↗

bioRxiv2025

Reflected Inline Detection in Epi Oblique Plane Microscopy

Epi oblique illumination selective plane microscopy (OPM) facilitates open-top, straightforward sample mounting, enabling high-resolution and high-speed imaging without perturbing biological specimens. However, current OPM systems typically require three separate microscopes equipped with specialized objectives. This configuration leads to complex and costly setups, significant long-term drift during imaging, reduced numerical aperture, and limited flexibility in adjusting the illumination tilt angle. We introduce Reflected Inline Detection in Epi-Oblique Plane Microscopy (RIDE-OPM), a novel, simplified, and cost-effective design that removes the necessity for a separate inline tertiary microscope and specialized objectives. Our tilt-angle-independent approach leverages the maximum NA of standard objectives, ensuring optimal illumination across the entire field of view without compromising imaging speed or quality, while significantly reducing long-term system drift. The compact and stable RIDE-OPM platform demonstrates robust, unsupervised long-term imaging capabilities. We validated this performance by successfully imaging various biological specimens, including C. elegans, Drosophila fly brain, human and mouse epithelial cells, and live E. coli, underscoring its suitability for advanced long-term biological imaging applications.

biophysics↗

bioRxiv2025

Cell-cycle-dependent cues regulate temporal patterning of the Drosophila central brain neural stem cells

During nervous system development, diverse types of neurons and glia are sequentially generated by self-renewing neural stem cells (NSCs). Temporal changes in gene expression within NSCs are thought to regulate neural diversity; however, the mechanisms regulating the timing of these temporal gene transitions remain poorly understood. Drosophila type 2 NSCs, like human outer radial glia, divide to self-renew and generate intermediate neural progenitors, amplifying and diversifying the population of neurons innervating the central complex, a brain region crucial for sensorimotor coordination. Type 2 NSCs express over a dozen genes temporally, broadly classified as early and late-expressed genes. A conserved gene, seven-up, mediates early to late gene expression by activating ecdysone receptor (EcR) expression. However, the timing of EcR expression and, consequently, the transition from early to late gene expression remains unknown. This study investigates whether intrinsic mechanisms of cell cycle progression and cytokinesis are required to induce the NSC early-late transition. By generating mutant clones that arrest the NSC cell cycle or block cytokinesis, we show that both processes are necessary for the early-to-late transition. When NSCs are cell cycle or cytokinesis arrested, the early gene Imp fails to be downregulated and persists in the old NSCs, while the late factors EcR and Syncrip fail to be expressed. Furthermore, we demonstrate that the early factor Seven-up is insufficient to drive the transition, despite its normal expression in cell cycle- or cytokinesis-inhibited NSCs. These results suggest that both cell-intrinsic (cell cycle/cytokinesis) and extrinsic (hormone) cues are required for the early-late NSC gene expression transition.

developmental biology↗

bioRxiv2023

Stem cell-specific ecdysone signaling regulates the development and function of a Drosophila sleep homeostat

Complex behaviors arise from neural circuits that are assembled from diverse cell types. Sleep is a conserved and essential behavior, yet little is known regarding how the nervous system generates neuron types of the sleep-wake circuit. Here, we focus on the specification of Drosophila sleep-promoting neurons--long-field tangential input neurons that project to the dorsal layers of the fan-shaped body neuropil in the central complex (CX). We use lineage analysis and genetic birth dating to identify two bilateral Type II neural stem cells that generate these dorsal fan-shaped body (dFB) neurons. We show that adult dFB neurons express Ecdysone-induced protein E93, and loss of Ecdysone signaling or E93 in Type II NSCs results in the misspecification of the adult dFB neurons. Finally, we show that E93 knockdown in Type II NSCs affects adult sleep behavior. Our results provide insight into how extrinsic hormonal signaling acts on NSCs to generate neuronal diversity required for adult sleep behavior. These findings suggest that some adult sleep disorders might derive from defects in stem cell-specific temporal neurodevelopmental programs.

neuroscience↗

bioRxiv2021

A neural circuit for wind-guided olfactory navigation

To navigate towards a food source, animals must frequently combine odor cues that tell them what sources are useful with wind direction cues that tell them where the source can be found. Where and how these two cues are integrated to support navigation is unclear. Here we identify a pathway to the Drosophila fan-shaped body (FB) that encodes attractive odor and promotes upwind navigation. We show that neurons throughout this pathway encode odor, but not wind direction. Using connectomics, we identify FB local neurons called h{Delta}C that receive input from this odor pathway and a previously described wind pathway. We show that h{Delta}C neurons exhibit odor-gated, wind direction-tuned activity, that sparse activation of h{Delta}C neurons promotes navigation in a reproducible direction, and that h{Delta}C activity is required for persistent upwind orientation during odor. Based on connectome data, we develop a computational model showing how h{Delta}C activity can promote navigation towards a goal such as an upwind odor source. Our results suggest that odor and wind cues are processed by separate pathways and integrated within the FB to support goal-directed navigation.

neuroscience↗

bioRxiv2019

Pdm3 directs sleep circuit development to control sleep maturation

Across species, sleep in young animals is critical for normal brain maturation. In contrast to mature adult sleep, the molecular determinants of early life sleep remain unknown. Through an RNAi-based screen, we identified a gene, pdm3, required for sleep maturation in Drosophila. Pdm3, a transcription factor, acts during nervous system development to coordinate the ingrowth of wake-promoting dopaminergic neurites to a sleep-promoting region. Loss of PDM3 prematurely increases dopaminergic inhibition of the sleep center, abolishing the juvenile sleep state. RNA-Seq/ChIP-Seq and a subsequent modifier screen reveal that pdm3 regulates expression of the synaptogenesis gene Msp300 to control sleep ontogeny. These studies define the molecular cues governing sleep behavioral and circuit development, and suggest sleep disorders may be of neurodevelopmental origin.

neuroscience↗

bioRxiv2017

Steroid Hormone Induction Of Temporal Gene Expression In Drosophila Brain Neuroblasts Generates Neuronal And Glial Diversity

An important question in neuroscience is how stem cells generate neuronal diversity. During Drosophila embryonic development, neural stem cells (neuroblasts) sequentially express transcription factors that generate neuronal diversity; regulation of the embryonic temporal transcription factor cascade is lineage-intrinsic. In contrast, larval neuroblasts generate longer {small tilde}50 division lineages, and currently only one mid-larval molecular transition is known: Chinmo/Imp/Lin-28+ neuroblasts transition to Syncrip+ neuroblasts. Here we show that the hormone ecdysone is required to down-regulate Chinmo/Imp and activate Syncrip, plus two late neuroblast factors, Broad and E93. We show that Seven-up triggers Chinmo/Imp to Syncrip/Broad/E93 transition by inducing expression of the Ecdysone receptor in mid-larval neuroblasts, rendering them competent to respond to the systemic hormone ecdysone. Importantly, late temporal gene expression is essential for proper neuronal and glial cell type specification. This is the first example of hormonal regulation of temporal factor expression in Drosophila embryonic or larval neural progenitors.\n\nSummaryHormone induction of temporal gene expression in neural progenitors

developmental biology↗