Biology subjects

Martinez-Abadias, N.

Publications and source records attributed to Martinez-Abadias, N..

4 recordsLinked to original sources

bioRxiv2023

Pleiotropic effects of trisomy and pharmacologic modulation on structural, functional, molecular, and genetic systems in a Down syndrome mouse model

Down syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental conditions. We overcame these limitations by conducting the first longitudinal controlled experiment evaluating genotype and GTE-EGCG prenatal chronic treatment effects before and after treatment discontinuation. Our findings revealed that the Ts65Dn mouse model reflected the pleiotropic nature of DS, exhibiting brachycephalic skull, ventriculomegaly, neurodevelopmental delay, hyperactivity, and impaired memory robustness with altered hippocampal metabolite concentration and gene expression. GTE-EGCG treatment modulated most systems simultaneously but did not rescue DS phenotypes. On the contrary, the treatment exacerbated trisomic phenotypes including body weight, tibia microarchitecture, neurodevelopment, adult cognition, and metabolite concentration, not supporting the therapeutic use of GTE-EGCG as a prenatal chronic treatment. Our results highlight the importance of longitudinal experiments assessing the co-modulation of multiple systems throughout development when characterizing preclinical models in complex disorders and evaluating the pleiotropic effects and general safety of pharmacological treatments.

systems biology↗

bioRxiv2020

A Method for the Automatic Normalization and 3D Facial Mesh Extraction from Head Magnetic Resonance Imaging

The analysis of 3D facial shape in medicine is motivated by the fact that certain diseases and syndromes are associated to specific facial dysmorphologies. In this context, 3D facial shape analysis constitutes a promising and non-invasive support to traditional diagnostic methods. In this work, we explore the use of head magnetic resonances to obtain accurate 3D facial meshes that enable subsequent facial shape analysis. We present a fully automatic method that normalizes the orientation and alignment of 3D point clouds corresponding to head magnetic resonances by detecting salient facial features. Moreover, using clustering techniques, our method also allows to eliminate noise and artifacts appearing in magnetic resonance imaging. Finally, through bidirectional ray tracing, we obtain a dense 3D facial mesh that accurately captures facial shape. The proposed method has been built and evaluated on a dataset of 185 head magnetic resonances, and it has demonstrated its ability to successfully orient, align and obtain a dense 3D facial mesh with a high accuracy rate.

bioinformatics↗

bioRxiv2018

Epigallocatechin-3-Gallate Improves Facial Dysmorphology Associated with Down Syndrome

In Down syndrome (DS), the overall genetic imbalance caused by trisomy of chromosome 21 leads to a complex pleiotropic phenotype that involves a recognizable set of facial traits. Several studies have shown the potential of epigallocatechin-3-gallate (EGCG), a green tea flavanol, as a therapeutic tool for alleviating different developmental alterations associated with DS, such as cognitive impairment, skull dysmorphologies, and skeletal deficiencies. Here we provide for the first time experimental and clinical evidence of the potential benefits of EGCG treatment to facial morphology. Our results showed that mouse models treated with low dose of EGCG during pre- and postnatal development improved facial dysmorphology. However, the same treatment at high dose produced disparate facial morphology changes with an extremely wide and abnormal range of variation. Our observational study in humans revealed that EGCG treatment since early in development is associated with intermediate facial phenotypes and significant facial improvement scores. Overall, our findings suggest a potential beneficial effect of ECGC on facial development, which requires further research to pinpoint the optimal dosages of EGCG that reliably improve DS phenotypes. Current evidence warns against the non-prescribed intake of this supplement as a health-promoting measure.

pathology↗

bioRxiv2018

Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis

The earliest developmental origins of dysmorphologies are poorly understood in many congenital diseases. They often remain elusive because the first signs of genetic misregulation may initiate as subtle changes in gene expression, which can be obscured later in development due to secondary phenotypic effects. We here develop a method to trace back the origins of phenotypic abnormalities by accurately quantifying the 3D spatial distribution of gene expression domains in developing organs. By applying geometric morphometrics to 3D gene expression data obtained by Optical Projection Tomography, our approach is sensitive enough to find regulatory abnormalities never previously detected. We identified subtle but significant differences in gene expression of a downstream target of the Fgfr2 mutation associated with Apert syndrome. Challenging previous reports, we demonstrate that Apert syndrome mouse models can further our understanding of limb defects in the human condition. Our method can be applied to other organ systems and models to investigate the etiology of malformations.

developmental biology↗