Biology subjects

Webster, K. A.

Publications and source records attributed to Webster, K. A..

3 recordsLinked to original sources

bioRxiv2025

Enteric neural crest development in Astyanax mexicanus surface fish and cavefish

The enteric nervous system (ENS) regulates gastrointestinal (GI) functions such as secretion, blood flow, and motility, yet how its structure and function evolve with dietary adaptations remains unclear. Astyanax mexicanus, a teleost fish with surface and cave morphotypes, offers a model to explore these changes; cavefish exhibit altered GI motility and transit that may help them adapt to their unique diet. We compared early ENS development in surface fish and cavefish, tracking enteric neural crest cell (ENCC) migration and differentiation using phox2bb and HuC/D markers. We found that ENCCs reach the gut by 36 hours post-fertilization (hpf) in both morphotypes but migrate and differentiate more rapidly along the gut tube in cavefish. To explore the genetic basis of this difference, we used available genomic datasets to compare the predicted peptide sequences of genes important for ENS development in other species and identified mutations that could impact protein function, for example in the endothelin signaling genes important for ENCC migration and differentiation. We specifically examined the expression of endothelin-3 (edn3) and endothelin receptor-b (ednrb) during ENCC migration and found that the localization of edn3, but not ednrb, is consistent with a role in ENS development. Overall, our findings position A. mexicanus as a model for studying evolution of ENS development.

developmental biology↗

bioRxiv2024

Differential expression of sex regulatory genes in gonads of Astyanax mexicanus surface fish and cavefish

BackgroundAstyanax mexicanus is a single species of fish that consists of river-dwelling (surface) and cave-dwelling morphotypes. Little is known about how sexual determination, differentiation or reproduction have evolved in the surface morphs or cavefish, though divergence in reproductive strategy is expected as the latter have adapted to the novel cave environment. Evolution of the gonad transcriptome may underlie the differences in gamete morphology, fertility, and fecundity previously reported between morphotypes. ResultsWe compared the ovary and testis transcriptome of surface fish and cavefish at juvenile and adult stages. We found that samples clustered by developmental stage, sex, and morphotype identity. Several key genes that are typically associated with the female gonad in other vertebrates showed a reversal in sexual dimorphism or were not differentially expressed between sexes in A. mexicanus. In contrast, while gene expression typically associated with male gonads was largely conserved and consistent with vertebrate testicular expression profiles. Transcriptional and physiological differences between surface fish and cavefish morphotypes were observed in gonads from both sexes. Cavefish ovaries exhibited unique upregulation of neuron development and differentiation genes, and extensive innervation of the ovarian epithelium, while cavefish testes showed increased expression of angiogenesis regulating genes, and greater vasculature density compared to surface fish testes. ConclusionsThese results reveal significant gene expression differences between A. mexicanus surface fish and cavefish morphotypes that may have functional consequences in gonad morphogenesis and fertility. Our findings provide a foundation for investigating the evolution of sex regulatory pathways and reproductive strategies in animals adapting to new and challenging environments in which nutrient availability, temperature, and mate selection are suboptimal.

evolutionary biology↗

bioRxiv2024

Sarcomeric SRX:DRX Equilibrium in Alport and LDLR/P407 Mouse Models of HFpEF.

Cardiac myosin energetic states that regulate heart contractility define interactions of myosin cross-bridges with actin-containing thin filaments have been functionally linked with the pathology of hypertrophic cardiomyopathy (HCM). In particular, the balance between the disordered relaxed (DRX) and super relaxed (SRX) states that correlate respectively with enhanced force and energy conservation significantly determine myocardial performance and energy utilization. Compelling evidence suggests that a balanced SRX and DRX states proportion is a prerequisite for long-term cardiac health. Whereas roles for altered SRX: DRX proportions in HCM have been studied in depth, the mechanics of sarcomeric dysfunction and SRX: DRX proportions have not been reported in models of acquired heart failure (HF) including HF with preserved ejection fraction (HFpEF). Here, we quantified SRX andDRX myosin populations in two mouse models of HFpEF, including Alport and LDLR/P407 mice that represent cardiorenal/hypertensive and cardiometabolic/hyperlipidemic mouse models of HFpEF, respectively. We report significant changes in the SRX:DRX in both HFpEF mouse models, with an increased DRX state associated with Alport mice and a stabilized SRX state associated with LDLR/P407 mice. These findings correlate respectively with the hypercontractility and metabolic dysregulation with bradycardia phenotypes.

cell biology↗