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Vidal-Garcia, M.

Publications and source records attributed to Vidal-Garcia, M..

6 recordsLinked to original sources

Cephalo-pelvic covariation and sexual dimorphism are disrupted in hybrid mice: implications for the human obstetrical dilemma

Cephalo-pelvic disproportion in humans has traditionally been interpreted through the obstetrical dilemma framework, assuming a trade-off between bipedal locomotion and childbirth. However, cephalo-pelvic covariation and pelvic sexual dimorphism might be common adaptations to parturition among mammals. We use a controlled hybridization model in mice to test whether cephalo-pelvic covariation and pelvic sexual dimorphism are population-specific, genetically structured, and sensitive to hybridization. We analyzed skull-pelvis variation and covariation, as well as sexual dimorphism of pelvic morphology across four divergent wild-derived mouse strains and their hybrids. Hybridization induced consistent cranial and pelvic size enlargement. Females exhibited significant cephalo-pelvic shape covariation, characterized by an association between rounder, wider birth canals and larger neurocrania, consistent with functional integration under obstetric selection. Hybrids showed disrupted size covariation, increased pelvis shape variance, and reduced cephalo-pelvic integration. Pelvic sexual dimorphism was systematically reduced in hybrids. Cephalo-pelvic covariation and pelvic sexual dimorphism are not exclusive to bipedal or encephalized species. They likely reflect widespread selection on birth canal morphology in mammals and have a complex genetic basis sensitive to hybridization. These findings weaken a human-exclusive interpretation of the obstetrical dilemma and highlight genetic introgression as an understudied factor shaping cephalo-pelvic integration and disproportion risk in mammals, including humans.

evolutionary biology↗

Downstream branches of receptor tyrosine kinase signaling act interdependently to shape the face

BackgroundPreviously we found that increasing fibroblast growth factor (FGF) signaling in the neural crest cells within the frontonasal process (FNP) of the chicken embryo caused dysmorphology that was correlated with reduced proliferation, disrupted cellular orientation, and lower MAPK activation but no change in PLCy and PI3K activation. This suggests RTK signaling may drive craniofacial morphogenesis through specific downstream effectors that affect cellular activities. In this study we inhibited three downstream branches of RTK signaling to determine their role in regulating cellular activities and how these changes affect morphogenesis of the FNP. ResultsSmall molecule inhibitors of MEK1/2, PI3K, and PLCy were delivered individually and in tandem to the right FNP of chicken embryos. All treatments caused asymmetric proximodistal truncation on the treated side and a mild expansion on the untreated side compared to DMSO control treated FNPs. Inhibiting each pathway caused similar decreased proliferation and disrupted cellular orientation, but did not affect apoptosis. ConclusionsSince RTK signaling is a ubiquitous and tightly regulated biochemical system we conclude that the downstream pathways are robust to developmental perturbation through redundant signaling systems. Bullet pointsInhibiting three downstream effectors of receptor tyrosine kinase (RTK) signaling (MEK1/2, PLCy, and PI3K) in the frontonasal process of chicken embryos caused similar mild truncation of growth. Combining all three inhibitors had a slightly stronger effect on truncation. Individual inhibitors did not have specific effects on cellular proliferation, apoptosis, or cellular orientation. The downstream branches of RTK signaling likely have shared interdependent effects on cellular activities that contribute to morphogenesis.

developmental biology↗

MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses

Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen (N=10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase (www.facebase.org, doi.org/10.25550/3-HXMC) and GitHub (https://github.com/jaydevine/MusMorph).

genetics↗

Segmentation of Tissues and Proliferating Cells in Light-Sheet Microscopy Images using Convolutional Neural Networks

Background and ObjectiveA variety of genetic mutations are known to affect cell proliferation and apoptosis during organism development, leading to structural birth defects such as facial clefting. Yet, the mechanisms how these alterations influence the development of the face remain unclear. Cell proliferation and its relation to shape variation can be studied in high detail using Light-Sheet Microscopy (LSM) imaging across a range of developmental time points. However, the large number of LSM images captured at cellular resolution precludes manual analysis. Thus, the aim of this work was to develop and evaluate automatic methods to segment tissues and proliferating cells in these images in an accurate and efficient way. MethodsWe developed, trained, and evaluated convolutional neural networks (CNNs) for segmenting tissues, cells, and specifically proliferating cells in LSM datasets. We compared the automatically extracted tissue and cell annotations to corresponding manual segmentations for three specific applications: (i) tissue segmentation (neural ectoderm and mesenchyme) in nuclear-stained LSM images, (ii) cell segmentation in nuclear-stained LSM images, and (iii) segmentation of proliferating cells in Phospho-Histone H3 (PHH3)-stained LSM images. ResultsThe automatic CNN-based tissue segmentation method achieved a macro-average F-score of 0.84 compared to a macro-average F-score of 0.89 comparing corresponding manual segmentations from two observers. The automatic cell segmentation method in nuclear-stained LSM images achieved an F-score of 0.57, while comparing the manual segmentations resulted in an F-score of 0.39. Finally, the automatic segmentation method of proliferating cells in the PHH3-stained LSM datasets achieved an F-score of 0.56 for the automated method, while comparing the manual segmentations resulted in an F-score of 0.45. ConclusionsThe proposed automatic CNN-based framework for tissue and cell segmentation leads to results comparable to the inter-observer agreement, accelerating the LSM image analysis. The trained CNN models can also be applied for shape or morphological analysis of embryos, and more generally in other areas of cell biology.

bioinformatics↗

The tiny Cretaceous stem-bird Oculudentavis revealed as a bizarre lizard

Oculudentavis khaungraae was described based on a tiny skull trapped in amber. The slender tapering rostrum with retracted osseous nares, large eyes, and short vaulted braincase led to its identification as the smallest avian dinosaur on record, comparable to the smallest living hummingbirds. Despite its bird-like appearance, Oculudentavis showed several features inconsistent with its original phylogenetic placement. Here we describe a more complete, specimen that demonstrates Oculudentavis is actually a bizarre lizard of uncertain position. The new interpretation and phylogenetic placement highlights a rare case of convergent evolution rarely seen among reptiles. Our results re-affirm the importance of Myanmar amber in yielding unusual taxa from a forest ecosystem rarely represented in the fossil record.

paleontology↗

ShapeRotator: an R package for standardised rigid rotations of articulated Three-Dimensional structures with application for geometric morphometrics

O_LIThe quantification of complex morphological patterns typically involves comprehensive shape and size analyses, usually obtained by gathering morphological data from all the structures that capture the phenotypic diversity of an organism or object. Articulated structures are a critical component of overall phenotypic diversity, but data gathered from these structures are difficult to incorporate in to modern analyses because of the complexities associated with jointly quantifying 3D shape in multiple structures.\nC_LIO_LIWhile there are existing methods for analysing shape variation in articulated structures in Two-Dimensional (2D) space, these methods do not work in 3D, a rapidly growing area of capability and research.\nC_LIO_LIHere we describe a simple geometric rigid rotation approach that removes the effect of random translation and rotation, enabling the morphological analysis of 3D articulated structures. Our method is based on Cartesian coordinates in 3D space so it can be applied to any morphometric problem that also uses 3D coordinates (e.g. spherical harmonics). We demonstrate the method by applying it to a landmark-based data set for analysing shape variation using geometric morphometrics.\nC_LIO_LIWe have developed an R tool (ShapeRotator) so that the method can be easily implemented in the commonly used R package geomorph and MorphoJ software. This method will be a valuable tool for 3D morphological analyses in articulated structures by allowing an exhaustive examination of shape and size diversity.\nC_LI

evolutionary biology↗