Biology subjects

Rasool, D.

Publications and source records attributed to Rasool, D..

3 recordsLinked to original sources

bioRxiv2026

TCF4 Mediates PHF6 Transcriptional Regulation of Neural Stem Cells in the Developing Brain, a Mechanism Disrupted in Börjeson Forssman Lehmann Syndrome (BFLS)

Transcriptional hierarchies govern neural stem cell (NSC) fate decisions during neurodevelopment, and disruption of these regulatory networks underlies neurodevelopmental disorders. Borjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability (XLID) caused by mutations in a chromatin-associated transcriptional regulator, the plant homeodomain zinc finger protein 6 (PHF6). Although BFLS mouse models harboring PHF6 patient mutations recapitulate neurogenic and cognitive deficits, the molecular mechanisms linking PHF6 dysfunction to these phenotypes remain poorly understood. Here, we identify transcription factor 4 (TCF4), a basic helix-loop-helix transcription factor implicated in neurodevelopmental and psychiatric disorders, as a critical downstream effector of PHF6 in NSC fate regulation. Tcf4 expression is reduced in BFLS mouse models harbouring R342X and C99F-m mutations and in a conditional Phf6 knockout driven by Nestin-Cre. Mechanistically, PHF6 binds the Tcf4 gene regulatory element upstream of its transcriptional start site (TSS) and promotes Tcf4 expression. Tcf4 depletion in embryonic NSCs enhances self-renewal and stemness, increasing neurosphere formation and expression of stem cell markers, Nestin and Sox2. Conversely, TCF4 restoration rescues NSC defects caused by PHF6 loss of function in BFLS and Phf6/Nestin-Cre mice. This regulatory relationship persists in adult NSCs where TCF4 similarly restricts stem cell expansion. Importantly, restoration of TCF4 expression in embryonic brain ameliorates behavioral and cognitive deficits in BFLS mice. Together, these findings establish a PHF6-Tcf4 transcriptional pathway that restricts NSC self-renewal and links disrupted transcriptional control of NSC fate to the neurodevelopmental and behavioral abnormalities of BFLS.

neuroscience↗

bioRxiv2026

The ASD Risk Gene D5Ertd579e Regulates Synaptic Plasticity and Selective Autism-Related Behaviors

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition shaped by contributions from hundreds of genes, many of which remain poorly characterized. This largely uncharacterized genomic landscape may therefore hold critical insight into how diverse molecular disruptions converge on shared social phenotypes. Here, we investigated KIAA0232 (mouse orthologue D5Ertd579e), an uncharacterized locus lacking known functional domains, using a global null knockout mouse model. While loss of D5Ertd579e did not overtly disrupt cortical progenitor dynamics, laminar organization, or gross brain morphology, D5Ertd579e null mutants exhibited selective behavioral deficits in vocalization, sociability, and novelty preference, while anxiety- and memory-related behaviors remained preserved. These behavioral phenotypes were accompanied by attenuated long-term plasticity, despite normal basal synaptic transmission. Together, our findings indicate that D5Ertd579e loss selectively alters neurodevelopment, preferentially impacting neural systems involved in social and motivational processing while preserving hippocampal-dependent networks. We propose that D5Ertd579e functions as a regionally specific regulator of neurodevelopment, whose disruption may contribute to ASD through distinct genetic pathways. More broadly, this study underscores the importance of interrogating uncharacterized loci to refine mechanistic models of the social brain in ASD.

neuroscience↗

bioRxiv2024

Identification and characterization of anti-epileptic compounds from Papaver somniferum using quantification techniques (GC-MS, FTIR), integrated network pharmacology, molecular docking, and molecular dynamics simulations

Epilepsy is a common neurological condition identified by repetitive seizures that affect the overall quality of life. Existing anti-epileptic drugs have undesirable side effects, necessitating safer alternatives. This study develops an integrated computational framework to discover potential anti-epileptic leads from Papaver somniferum (opium poppy). Literature and databases were mined to compile all chemicals from Papaver somniferum. PubChem provided structural data, and compounds satisfying drug-likeness and bioavailability criteria were selected. GeneCards, DisGeNET and SwissTargetPrediction identified 344 target genes of the compounds and common targets with epilepsy. Network pharmacology analyses were performed. Cytoscape constructed a compound-target network comprising 5 active constituents and 22 shared targets. Degree distributions revealed molecular interactions. STRING elucidated target connectivity. Hub targets were identified using CytoHubba. GO and KEGG enrichment on 123 targets recognized biological roles and pathways. DAVID and Hiplot characterized functional annotations. Cytoscape visualized a compound-target-pathway association network involving targets, pathways, and compounds related to epilepsy. GC-MS identified 25 compounds in the Papaver somniferum extract. FTIR characterized functional groups. Molecular docking scored compound affinities for 10 targets. Autodock Vina docked 15 constituents into binding pockets. Interactions were validated using Desmond MD simulations of IL6 with scoulerine over 100 ns, assessing RMSD, RMSF, interactions. RMSD/RMSF plots and histograms characterized protein/ligand stability and flexibility. This integrative Insilico and Invitro framework facilitates prioritizing Papaver somniferum constituents for epilepsy. Network analyses provided systems-level understanding of multi-target mechanisms. Molecular modeling established structure-activity relationships, validating predicted interactions. Compounds with good ADMET profiles, network centrality, docking scores, and stable simulations emerge as candidates warranting further examination for safer anti-epileptic therapy.

bioinformatics↗