Biology subjects

Guerrero-Pena, L.

Publications and source records attributed to Guerrero-Pena, L..

4 recordsLinked to original sources

bioRxiv2025

Genetic ablation of Pth4 disrupts calcium-phosphate balance, bone development, and kidney transcriptome in teleosts

Parathyroid hormone 4 (Pth4) is an evolutionarily conserved member of the PTH family, expressed in hypothalamic neurons and lost in eutherian mammals. In order to elucidate its role in mineral homeostasis and skeletal development, a pth4 knockout (pth4KO) zebrafish line was generated using CRISPR/Cas9 and transcriptomic profiling was conducted across six key tissues: brain, kidney, intestine, gills, scales, and bone. The results obtained demonstrated that the loss of Pth4 led to pronounced disturbances in calcium and phosphate homeostasis, skeletal deformities, and widespread tissue-specific transcriptional alterations. Notably, dysregulation of mineral regulatory genes-- such as fgf23, phex, and slc34a1a was particularly evident in the kidney, suggesting disruption of the FGF23-Klotho axis. In parallel, differential expression of extracellular matrix genes (col1a1a, col10a1a, col11a1) and matrix remodeling enzymes (mmp9, mmp13a, mmp2) in bone and scales indicated impaired skeletal remodeling. Together, these findings highlight a pivotal role for Pth4 in the endocrine and local regulation of mineral metabolism and skeletal integrity, expanding our understanding of PTH family functions in vertebrate physiology.

developmental biology↗

bioRxiv2025

alms1 regulates the immune response and brain ageing in zebrafish

The ALMS1 gene plays a crucial role in maintaining cellular homeostasis through its involvement in primary cilium assembly, cytoskeletal regulation, and signalling pathways such as NOTCH and TGF-{beta}. Pathogenic variants in ALMS1 are associated with Alstrom Syndrome (ALMS), a multi-systemic ciliopathy characterised by neurosensory deficits, metabolic disorders, and multi-organ fibrosis. To better understand the tissue-dependent role of ALMS1, we utilised CRISPR/Cas9 technology to develop a zebrafish model with alms1 depletion. Multi-tissue transcriptomic profiling revealed that alms1 depletion has pleiotropic effects on gene expression, with the brain and eyes displaying the most pronounced transcriptomic alterations, including disrupted ciliary function and immune dysregulation. Inflammatory and innate immune pathways along with glutamatergic synapse-related processes were significantly affected in the brain and eyes but with different gene expression signatures. The analysis further highlights tissue-specific processes, primarily associated with organ dysfunction. Additionally, our findings underscore the role of alms1 in regulating age-associated gene expression profiles in the brain, suggesting a link between ciliary dysfunction and accelerated brain ageing. Comparative analyses with Bardet-Biedl Syndrome iPSC models revealed shared pathways, reinforcing the potential of ciliopathies as models for ageing-related disorders. This study provides novel insights into the tissue-specific functions of alms1 and the molecular mechanisms underlying ALMS, paving the way for the development of targeted therapeutic strategies.

genomics↗

bioRxiv2025

Epigenetic Regulation of Visual System Remodeling During Flatfish Metamorphosis: DNA Methylation Dynamics in Ocular Migration and Visual Adaptation

Flatfish metamorphosis is characterized by extensive tissue remodeling, associated with a transition from pelagic to benthic lifestyle, being the migration of one eye the most dramatic change. Epigenetic mechanisms exert a pivotal role in developmental programs. This study investigates the DNA methylation profiles of migrating and non-migrating eyes using reduced-representation bisulfite sequencing (RRBS) during three developmental stages of turbot: pre-metamorphosis, climax and post-metamorphosis. Over 31% of all identified regions were hypermethylated during climax stage in both eyes, coinciding with elevated expression of the dnmt3a gene, responsible for de novo methylation. Additionally, transcription factors crucial for retinal ganglion cells (RGCs) development, including the eomesa and tbr1b, exhibited differential methylation and expression between the migrating and non-migrating eye during the climax phase. These findings underscore the significance of DNA methylation in the intricate remodeling of the visual system during turbot metamorphosis, particularly regarding RGC-mediated ocular migration and the transmission of visual signals.

molecular biology↗

bioRxiv2025

Epigenetic Regulation During Flatfish Metamorphosis: Integrative Omics Analysis of DNA Methylation and Gene Expression in Turbot Brain

The regulation of gene expression plays a pivotal role in the complex metamorphic process of flatfishes, which oversees the dynamic alterations that occur during their transition from a pelagic to a benthic way of life. Flatfish metamorphosis is characterized by substantial modifications in both form and function, which are initiated by thyroid hormones. Epigenetic mechanisms play a vital role in the regulation of gene expression during this transformative process. This study examines the molecular mechanisms underlying flatfish metamorphosis by integrating multi-omics data that provide information on chromatin status, DNA methylation profile, and gene expression at three key stages (pre-metamorphosis, climax and post-metamorphosis) in the turbot (Scophthalmus maximus) brain, a complex organ that plays a critical role in the regulation of this intricate process. The analysis of DNA methylation patterns revealed major epigenetic dynamic changes during the different metamorphosis stages. Specifically, the methylation levels exhibited a typical bimodal distribution in the pre-metamorphic stage, transitioned to intermediate levels of methylation (around 50%) during the climax stage, and reverted to a bimodal distribution in the post-metamorphic stage. Notably, DMRs were identified in regions of open chromatin that colocalized with CpG islands. Moreover, our results indicate an inverse relationship between DNA methylation and transcriptional activity in regions near the transcription start sites (TSSs), where high levels of methylation correspond to low expression and low levels of methylation corresponds to high gene transcription. This study thereby elucidates the regulatory impact of methylation on gene expression during the metamorphosis process in the flatfish brain.

molecular biology↗