Biology subjects

Zaghloul, N.

Publications and source records attributed to Zaghloul, N..

4 recordsLinked to original sources

bioRxiv2025

Genetic architecture of the developing forelegs of Drosophila prolongata; an exaggerated weapon and ornament

Extreme secondary sexual traits are some of the most striking phenotypes in nature. Studies on the genetics of these phenotypes have largely focused on within-species functional analyses of signalling pathways. Although useful, these do not provide insight into the evolutionary mechanisms that occur during the evolution of trait exaggeration. Drosophila prolongata offers an exceptional opportunity to explore the evolution of trait exaggeration, as it is the only species in the melanogaster species group with male-specific foreleg size exaggeration under both intra- and intersexual selection. Here, we used sex-specific RNA-seq from fore- and midleg tissues during early development and after initiation of sexually dimorphic growth between these tissues in D. prolongata. We also sampled the same developmental stages in D. carrolli ([~]4MYA divergence) and D. melanogaster ([~]20MYA). Using comparisons of gene expression between sexes, species, tissues, and developmental stages, we found a positive relationship between the number, but not the magnitude of differential expression of sex-biased genes, with the extent of phenotypic dimorphism. One gene with a large effect, grain, caused D. prolongata-like leg size phenotypes in D. melanogaster legs when knocked down. We further found only modest changes to magnitude and direction of expression differences in signalling pathways previously implicated in sexually dimorphic evolution. This suggests that these pathways regulating trait expression and dimorphism but may not be primary drivers of their phenotypic evolution. Significance statementHow sexes evolve distinct forms while developing from a shared genome continues to be incompletely resolved. We explore a sexually dimorphic exaggerated trait, enlarged forelegs in Drosophila prolongata, and compare changes in sex-biased gene expression between tissues and developmental stages in D. prolongata and two closely related species without foreleg exaggeration. We show that major developmental pathways dont appear to change substantially in their direction or magnitude of expression between species. We further show a transcription factor, grain, that when knocked-down, induces D. prolongata leg-like phenotypes in D. melanogaster at low penetrance. Our results suggest that despite large morphological differences and patterns of dimorphism, gene expression changes between the developing tissues may be more modest than previously thought.

evolutionary biology↗

bioRxiv2025

A New Pathway for the Decussation of Corticospinal Tracts

Each brain hemisphere controls the movements of the opposite side of the body because the motor axons cross the midline, known as CST decussation. The current theory on CST decussation suggests CSTs decussate as a single tract at the junction between medulla and spinal cord. Although this theory is widely accepted, this theory is based on selective analyses and is therefore incomplete. Here, we employed new approaches, including the horizontal analyses and a non-invasive anterograde tracing method to examine CST decussation thoroughly. We analyzed all CS axons in 3 planes. These approaches led to the discovery of a new pathway for CST decussation. We found CSTs turned back to medulla, moving anteriorly and decussated in an oval structure. In this structure, each CST split into 4 fascicle groups and interdigitated with the corresponding groups from the opposite CST to cross the midline. The significance of this pathway was apparent after decussation where these 4 groups reversed direction, moving posteriorly toward spinal cord. While moving, the motor axons gradually separated at different locations and subsequently turned and occupied the correct positions in the dorsal funiculus for proper limb control. In addition to CSTs, we also characterized several components in the oval structure.

neuroscience↗

bioRxiv2022

Mapping fetal myeloid differentiation in airway samples from premature neonates with single-cell profiling

Single-cell genomic technologies hold great potential to advance our understanding of development and disease. A major limitation lies in isolating intact cells from primary tissues for profiling. Sampling methods compatible with current clinical interventions could enable longitudinal studies, the enrollment of large cohorts, and even the development of novel diagnostics. To explore single-cell RNA-seq (scRNA-seq) profiling of the cell types present at birth in the airway lumen of extremely premature (<28 weeks gestation) neonates, we isolated cells from endotracheal aspirates collected from intubated neonates within the first hour after birth. We generated data on 10 subjects, providing a rich view of airway luminal biology at a critical developmental period. Our results show that cells present in the airways of premature neonates primarily represent a continuum of myeloid differentiation, including fetal monocytes (25% of all cells), intermediate myeloid populations (48% of cells), and macrophages (2.6% of cells). To our knowledge, this is the first single-cell transcriptomic characterization of human monocytes in the neonatal airway isolated within an hour of birth. Applying trajectory analysis to the premature neonate myeloid populations, we identified two trajectories consistent with the developmental stages of interstitial and alveolar macrophages, as well as a third trajectory presenting a potential alternative pathway bridging these terminal macrophage states. While the three trajectories share many dynamic genes (5,451), they also have distinct transcriptional changes (259 alveolar-specific genes, 666 interstitial-specific genes, and 285 bridging-specific genes). Overall, our results define high quality single-cell data from cells isolated within the so-called "golden hour of birth" in extremely premature neonate airways representing complex lung biology and can be utilized in studies of human development and disease.

developmental biology↗

bioRxiv2020

Extracellular Superoxide Dismutase (EC-SOD) Regulates Gene Methylation and Cardiac Fibrosis During Chronic Hypoxic Stress.

BackgroundChronic hypoxic stress induces epigenetic modifications in cardiac fibroblasts, such as inactivation of tumor suppressor genes (RASSF1A), and activation of kinases (ERK1/2). The effects of the antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), on these epigenetic changes has not been fully explored. ObjectivesTo define the effect of EC-SOD overexpression on cardiac fibrosis induced by chronic hypoxia. MethodsWild type C57B6 male mice (WT) and transgenic males with an extra copy of human hEC-SOD (TG) were housed in hypoxia (10% O2) for 21 days. Right ventricular tissue was studied for cardiac fibrosis markers using RT-PCR and Western Blot analyses. Downstream effects were studied, for both RASSF-1 expression and methylation and its relation to ERK1/2, using in-vivo & in-vitro models ResultsThere were significant increases in markers of cardiac fibrosis : Collagen 1, Alpha Smooth Muscle Actin (ASMA) and SNAIL, in the WT hypoxic animals as compared to the TG hypoxic group (p< 0.05). Expression of DNA methylation enzymes (DNMT 1,2) was significantly increased in the WT hypoxic mice as compared to the hypoxic TG mice (p<0.001). RASSF1A expression was significantly lower and ERK1/2 was significantly higher in hypoxia WT compared to the hypoxic TG group (p<0.05). Use of SiRNA to block RASSF1A gene expression in murine cardiac fibroblast tissue culture led to increased fibroblast proliferation (p<0.05). Methylation of RASSF1A promoter region showed a significant reduction in the TG hypoxic group compared to the WT hypoxic group (0.59 vs 0.75 respectively). ConclusionsEC-SOD significantly attenuates RASSF1A gene methylation, and plays a pivotal role cardiac fibrosis induced by hypoxia.

developmental biology↗