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Biology subjects

Madrzyk, M.

Publications and source records attributed to Madrzyk, M..

4 recordsLinked to original sources

Social isolation is associated with microRNA expression changes in the visual system of poison frog tadpoles

Brain microRNA (miRNA) expression can shift in response to the social environment, translating external cues into regulatory action that can influence brain structure, neural activity, and behavior. miRNAs are key drivers of behavioral flexibility, regulating gene networks involved in neuroplasticity. We manipulated social rearing conditions of brilliant-thighed poison frog tadpoles (Allobates femoralis) to test whether isolation-linked behavioral changes are associated with altered miRNA expression in the midbrain and eyes, tissues linked by the retinotectal tract, a known connection for trafficked precursor miRNAs. We asked whether isolation alters visually guided behavior using a light/dark preference assay and found that isolated tadpoles spent less of the trial on the dark side than did group-housed tadpoles. In a social place preference assay, group-housed tadpoles preferred a zone near a conspecific over an object control when provided with multimodal sensory access, but not when access was restricted to vision alone. We next tested whether social rearing conditions influenced miRNA expression and found that isolated tadpoles exhibited upregulation of miR-15-P1c_3p*, the canonically non-dominant arm of an understudied miRNA, in the midbrain and eyes. We detected a shift in arm dosing for miR-124, a miRNA with conserved roles in neural differentiation and plasticity. Finally, social isolation during development was associated with downregulation of parathyroid hormone 2 (pth2), a peptide associated with social isolation and mechanosensation in other aquatic larvae. This work contributes to a growing body of literature implicating miRNAs in developmental neuroplasticity, presenting precedented and novel signatures of the transcriptional and regulatory response to isolation.

neuroscience↗

Diet quality shapes development and feeding circuits in poison frog tadpoles

From birth, offspring must balance internal energy state with the costs of signaling need to caregivers to secure nutrition for growth and healthy development. How diet during this period shapes the developing brain and behavior is a central question in biology, with growing relevance for understanding the developmental origins of metabolic disorders such as obesity. Yet the effects of early nutrition on growth, neural development, and behavior are rarely examined together within a single system. Here, we use poison frog tadpoles as a vertebrate model in which offspring develop outside a womb, can be reared independently under precisely controlled dietary conditions, and display diverse behaviors at a young age. By independently manipulating dietary quantity and quality, we link early nutrition to growth, brain development, and social behavior during ontogeny. Diet quantity increased body size, whereas diet quality accelerated development. Diet quality, but not quantity, shaped behavior: tadpoles fed a natural diet showed increased affiliation during food solicitation and reduced feeding, while aggression and risk avoidance remained unchanged. Diet also affected body and brain development differently, with artificial diets producing larger tadpoles but reduced volume in some brain regions, including areas associated with begging behavior. Anorexigenic urocortin-1 neurons were active during begging behavior and, together with another anorexigenic midbrain population, decreased in abundance under an artificial diet. Functionally, urocortin-1 reduced feeding without directly increasing begging, suggesting it gates socio-positive behavior by suppressing a competing drive rather than initiating it. Together, this work shows that dietary quantity and quality act on distinct developmental processes, with diet quality programming the brain circuits that permit begging behavior while growth is determined by food quantity.

neuroscience↗

Insertion of an invading retrovirus regulates a novel color trait in swordtail fish

For over a century, evolutionary biologists have been motivated to understand the mechanisms through which organisms adapt to their environments. Coloration and pigmentation are remarkably variable within and between species and can serve as an important window into the mechanisms of adaptation. Here, we map the genetic basis of a newly described iridescence trait in swordtail fish to a single locus. Individuals with this trait appear to sparkle as they move through the water. We find that the trait is driven by the recent endogenization of a retrovirus that inserted near the gene alkal2a. This insertion is associated with changes in the chromatin landscape, upregulation of alkal2a, and accumulation of iridescent cells that adhere to the scales. Rather than causing diseases, our results demonstrate that invading endogenous retroviruses can also regulate novel trait variation in the host. Moreover, we find that this coloration trait may act as an important signal in interactions between fish and their predators in the natural environment.

evolutionary biology↗

Molecular portraits of colorectal cancer morphological regions

Heterogeneity of colorectal carcinoma (CRC) represents a major hurdle towards personalized medicine. Efforts based on whole tumor profiling demonstrated that the CRC molecular subtypes were associated with specific tumor morphological patterns representing tumor subregions. We hypothesize that whole- tumor molecular descriptors depend on the morphological heterogeneity with significant impact on current molecular predictors. We investigated intra-tumor heterogeneity by morphology-guided transcriptomics to better understand the links between gene expression and tumor morphology represented by six morphological patterns (morphotypes): complex tubular, desmoplastic, mucinous, papillary, serrated, and solid/trabecular. Whole-transcriptome profiling by microarrays of 202 tumor regions (morphotypes, tumor-adjacent normal tissue, supportive stroma, and matched whole tumors) from 111 stage II-IV CRCs identified morphotype-specific gene expression profiles and molecular programs and differences in their cellular buildup. The proportion of cell types (fibroblasts, epithelial and immune cells) and differentiation of epithelial cells were the main drivers of the observed disparities with activation of EMT and TNF- signaling in contrast to MYC and E2F targets signaling, defining major gradients of changes at molecular level. Several gene expression-based (including single-cell) classifiers, prognostic and predictive signatures were examined to study their behavior across morphotypes. Most exhibited important morphotype-dependent variability within same tumor sections, with regional predictions often contradicting the whole-tumor classification. The results show that morphotype-based tumor sampling allows the detection of molecular features that would otherwise be distilled in whole tumor profile, while maintaining histopathology context for their interpretation. This represents a practical approach at improving the reproducibility of expression profiling and, by consequence, of gene-based classifiers.

cancer biology↗