Biology subjects

Amal, H.

Publications and source records attributed to Amal, H..

3 recordsLinked to original sources

bioRxiv2026

TGF-β signaling regulates epithelial permeability in Drosophila ovaries by modulating adhesion independent of actomyosin contractility

Epithelial morphogenesis and homeostasis rely on dynamic remodeling of cell-cell junctions. Tricellular junctions (TCJs) at cell vertices are key sites that control epithelial permeability and plasticity, yet how TCJs are remodeled remains unclear. In the follicular epithelium (FE) in Drosophila ovaries, TCJs open transiently in a process called patency to allow passage of yolk proteins for uptake by the oocyte. We investigated how a gradient of TGF-{beta} signaling activity suppresses patency in a graded manner across the FE. We show that TGF-{beta} signaling blocks patency in a cell-autonomous manner by strengthening E-Cadherin (E-Cad)-based adhesion through inducing E-Cad transcription and preventing its removal from cell vertices. In parallel, TGF-{beta} signaling activates myosin II through Rho-Rok signaling. However, myosin II activity is dispensable for TGF-{beta}-mediated suppression of patency. We show that TGF-{beta} signaling controls TCJ remodeling in follicle cells primarily by reinforcing E-Cad-based adhesion, in part through upregulating p120-catenin. Our findings disentangle the roles of adhesion and actomyosin contractility in maintaining TCJ integrity and reveal how a tissue-scale morphogen gradient is translated into graded epithelial permeability.

developmental biology↗

bioRxiv2025

Brain-Wide Subnetworks within and between Naturally Socializing Typical and Autism Model Mice

Social interaction is inherently asymmetric, requiring coordinated activity between non-homologous brain regions across individuals. However, the brain-wide dynamics underlying such inter-brain coordination remain poorly understood. We used multi-fiber photometry to simultaneously record from 24 brain regions in pairs of freely interacting mice, including a model of autism. Social interactions evoked widespread, dynamic activity across brains, with inter-brain synchrony, especially between non-homologous areas, exceeding intra-brain synchrony, particularly in dominant mice. Network analysis revealed three subnetworks: (1) Emotional, intra-brain enhanced in subordinates; (2) Sensory, spanning both mice; (3) Decision/consolidation, linking dominant prefrontal cortex to subordinate hippocampus. These subnetworks encoded dominance, identity, and interaction roles, and followed a clear temporal sequence around social events. In an autism model, socially evoked activity was hyperactive displaying mostly within brain synchrony but lacked inter-brain synchrony. Our results uncover dynamic inter-brain circuits as a hallmark of social behavior and reveal their disruption in autism.

neuroscience↗

bioRxiv2023

The NO Answer for Autism Spectrum Disorder

Autism spectrum disorders (ASDs) include a range of developmental disorders that share a core of neurobehavioral deficits manifested by abnormalities in social interactions, deficits in communication, restricted interests, and repetitive behaviors. Several reports showed that mutations in different high-risk ASD genes, including SHANK3 and CNTNAP2, lead to ASD. However, to date, the underlying molecular mechanisms have not been deciphered, and no effective pharmacological treatment has been established for ASD. Recently, we reported a dramatic increase of nitric oxide (NO) in ASD mouse models. NO is a multifunctional neurotransmitter that plays a key role in different neurological disorders. However, its role in ASD has not yet been investigated. To reveal the novel molecular, cellular, and behavioral role of NO in ASD, we conducted multidisciplinary experiments using cellular and mouse models as well as clinical samples. First, we treated WT mice with an NO donor, which led to an autism-like phenotype. Next, we measured and found high levels of nitrosative stress biomarkers in both the Shank3 and Cntnap2 ASD mouse models. Treating both mouse models with a selective neuronal NO synthase (nNOS) inhibitor led to a reversal in the molecular, synaptic, and behavioral ASD phenotypes. Using a primary neuronal cell culture, we confirmed that NO is specifically involved in neurons in ASD pathology. Next, using genetic manipulations in the human SH-SY5Y cell line, we found that nNOS plays a key role in the pathology. Finally, we examined human plasma samples from 19 low-functioning ASD patients, compared to 20 typically developed volunteers, and found a significant elevation in the NO levels in the ASD patients. Furthermore, using the SNOTRAP technology, which is an innovative mass spectrometric method to identify the SNO-proteome (SNO: NO-mediated post-translational modification), we revealed that the complement systems in the synaptic and neuronal development processes are enriched in the ASD group. This work indicates, for the first time, that NO plays a pathological role in ASD development. Our findings will open future and novel directions to examine NO in diverse mutations on the autism spectrum as well as other neurodevelopmental disorders and psychiatric diseases. Most importantly, it suggests a novel treatment strategy for ASD. One sentence summaryNitric oxide plays a key role in ASD pathology development and progression, and targeting its production leads to a reversal in the autistic phenotype.

neuroscience↗