bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.10.14.759140

Unilateral gene expression via maternally controlled zygotic recombination in Drosophila

Currier, T. A.·Tadres, D.·Troper, J. E.·Wang, Y.·Clandinin, T. R.
View original source ↗Export metadata ↓

Abstract

Structural and functional asymmetries are ubiquitous in bilaterians, but tools for unilateral genetic access have been lacking, a methodological gap that has limited mechanistic dissections of lateralized cellular functions. We developed the Maternally Controlled Zygotic Recombination (MCZR) system to overcome this limitation in Drosophila, co-opting the regulatory machinery of the maternal-to-zygotic transition to enable somatic recombination during early embryonic development. Targeting recombinase activity to this early window generates large somatic mosaics that frequently split across the anatomical midline. In conjunction with cell type-specific driver lines, this approach provides a reliable, scalable, and user-friendly platform for unilateral transgene expression. In proof-of-concept experiments, we apply our tool to the question of locomotor control, illustrating how MCZR can be used to unilaterally manipulate or monitor a cell type of interest. Overall, the MCZR system unlocks previously inaccessible experimental avenues across neuroscience, cell biology, and developmental biology.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Currier, T. A., Tadres, D., Troper, J. E., Wang, Y., Clandinin, T. R.. 2026-10-16. Unilateral gene expression via maternally controlled zygotic recombination in Drosophila. https://doi.org/10.64898/2026.10.14.759140

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Three-dimensional object-based quantification of nicotinic acetylcholine receptor subunit colocalization using Imaris

Neural circuit function depends not only on synaptic connectivity but also on the molecular composition and spatial organization of neurotransmitter receptors. Determining whether receptor subunits occupy shared or distinct domains requires spatial measurements capable of resolving sparse receptor puncta across neural tissue and, when needed, restricting analysis to defined cellular compartments. Conventional intensity-based colocalization metrics can be difficult to interpret for sparse, punctate signals and do not inherently provide object-level classification or cell-specific analysis. Here, we describe a three-dimensional object-based colocalization workflow for endogenously tagged nicotinic acetylcholine receptor (nAChR) subunits imaged by Airyscan super-resolution confocal microscopy and analyzed in Imaris. Individual receptor puncta are segmented as 3D surface objects and classified as colocalized or non-colocalized using a control-defined spatial overlap criterion. The workflow supports analysis within a defined region of the ventral nerve cord neuropil or within genetically labeled motor-neuron dendritic compartments. For dendrite-restricted analysis, receptor puncta are first selected by their overlap with the dendritic surface before receptor-receptor overlap is quantified. The overlap criterion is empirically calibrated using positive and negative biological controls processed under the same imaging and analysis conditions, providing a reproducible alternative to arbitrary threshold selection. This approach enables receptor organization to be quantified within the neuropil and genetically labeled motor-neuron dendritic compartments and can be adapted to other epitope-tagged receptors, ion channels, and synaptic proteins.

neuroscience↗
bioRxiv2026

Hidden Markov Modeling Reveals Altered Functional Network Dynamics in Multiple Sclerosis

Purpose: Multiple sclerosis (MS) is a neurodegenerative and demyelinating disease of the central nervous system. Recent evidence suggests that localized gray matter atrophy in MS may be involved in distributed functional brain networks. However, the dynamic trajectory of functional network alterations in MS remains unclear. The current study extends prior network-mediated findings and aims to investigate the dynamic functional connectivity (dFC) and energetic landscape across an atrophy-prone network in MS. Methods: Twenty MS participants and twenty healthy controls (HC) underwent resting-state fMRI. The atrophy-based functional network (AFN) model was implemented, and time series from atrophy-prone regions were fit to a 12-state hidden Markov model. Each functional network state, a recurring pattern of activity across the AFN, was characterized by the AFN regions with the strongest activation. The states were then grouped into two metastates. Dynamic functional network metrics were compared between groups by permutation testing and correlated with disability and cognition. The energetic landscape of the network was mapped with a pairwise maximum-entropy model. Temporal irreversibility was also measured, which defines the arrow-of-time asymmetry of network dynamics. Results: People with MS showed lower occupancy of state 1, which peaked on the right middle frontal and anterior cingulate cortex. Occupancy and mean lifetime were higher in states 3 and 10 (p < 0.05). In state 3, cortical activity was below the network average, and state 10 peaked on the postcentral gyrus. At the metastate level, MS participants spent more time in metastate M1 and less in M2 (p = 0.04). Within the MS group, a longer interval between visits to state 3 was associated with greater disability (r = 0.57), and a higher switching rate in state 10 with poorer verbal fluency (r = -0.50). The energetic landscape was similar between groups. Temporal irreversibility was lower in MS, mainly across subcortical connections. Conclusion: MS participants dwelled longer in specific dFC states of the AFN, while the rate of transition between states did not differ from healthy controls. Dynamic functional network metrics were associated with disability and cognitive performance and may serve as functional correlates of clinical impairment. The states were similar between groups, whereas the directed drive between states was lower across subcortical connections. This pattern suggests altered network dynamics rather than altered network architecture in MS. Findings from this study characterize the functional network dynamics of neurodegeneration in MS, which may inform future development of network-based approaches for monitoring disease progression.

neuroscience↗
bioRxiv2026

LATS2 modulates synaptic organization and function by regulating actin dynamics

Recent work has highlighted the importance of core Hippo pathway kinases in cycling cells. Many of these kinases are also expressed in post-mitotic neurons, where they have been linked to synaptic function, and more recently a number have been shown to be dysregulated in neurodegenerative diseases such as Alzheimers disease. Despite this, little is known about the specific role or subcellular localization of the Large Tumor Suppressor kinases, LATS1 and LATS2, in postmitotic neurons. Previously, we demonstrated that LATS1 plays an important role in synapse development; however, the role of LATS2 remains poorly understood. Here, we examined the distribution and function of LATS2 and found that it is highly expressed in CA3/CA4 neurons of the hippocampus and localized throughout dendrites and dendritic spines. In contrast to LATS1, LATS2 expression remains stable throughout neuronal development. Furthermore, ectopic expression of LATS2 induces kinase-dependent structural spine defects, alters actin dynamics and reduces activity-dependent synaptic SEP-GluR1 fluorescence. Collectively, these findings reveal a unique distribution LATS2 in the hippocampus and demonstrate that LATS2 directly regulates actin dynamics and GluR1-containing AMPAR trafficking.

neuroscience↗