Biology subjects

Garcia, K. E.

Publications and source records attributed to Garcia, K. E..

5 recordsLinked to original sources

bioRxiv2026

A Mechanical Theory for the Formation of Short Association Fibers in the Brain

The development of neural connections in the brain results from a complex interplay between biological processes and mechanical forces. A key question in neuroscience is how physical forces and the mechanical properties of brain tissue influence the formation of structural connections. Here, we demonstrate that mechanical forces play an essential role in shaping the emergence of short-range connections, particularly U-shaped fibers that link neighboring regions of the cortex. Using a computational model that incorporates our "stress-dependent axon reorientation" hypothesis, we simulate how growing axons respond to the mechanical stress field generated by cortical folding. Our results suggest that axonal growth and reorientation may be strongly influenced by local mechanical cues, helping establish the organization of these short-range pathways. Supported by in vivo diffusion tensor imaging and histological observations, our findings provide a physical explanation for why these fibers predominantly adopt U-shaped trajectories, and why connections between gyri (ridges) are more prevalent than those between sulci (valleys) or spanning gyri and sulci. These results suggest that understanding the mechanics of brain folding is critical for fully explaining the formation of brain connectivity and its variations in health and disorder. Teaser: Mechanical forces during cortical folding guide the formation of short association fibers in the brain.

bioengineering↗

bioRxiv2025

Differential patterns of cortical expansion in fetal and preterm brain development

The human cerebral cortex undergoes a complex developmental process during gestation, characterised by rapid cortical expansion and gyrification. This study investigates in vivo cortical growth trajectories using longitudinal MRI data from fetal and preterm cohorts. We employed anatomically constrained multimodal surface matching (aMSM) to quantify cortical surface area expansion and compare in-utero versus ex-utero cortical growth using cortical surface data from 22 to 44 weeks post-menstrual age (PMA), acquired as part of the Developing Human Connectome Project (dHCP). Our findings revealed distinct regional and temporal growth patterns during the 2nd and 3rdrd trimesters of healthy fetal cortical expansion. Ex utero brain development following preterm birth was shown to follow a modified trajectory compared to normal gestation, with potential implications for cortical organisation. Our methodology, combining biomechanically constrained surface registration with high quality fetal and neonatal imaging, provides a powerful framework for understanding early cortical development and deviations associated with preterm birth.

neuroscience↗

bioRxiv2025

Measurement of residual stress in the brain

Mechanical stress in brain tissue is an important feature of the brain, likely to play key roles in brain development and brain injury. Here, we characterize residual stresses in grey matter and white matter from the deformed shape of tissue cylinders extracted from the brain using a biopsy needle and imaged with high-resolution magnetic resonance imaging (MRI). We use finite element simulations to reconstruct the stress state of tissue sections in the intact brain from images of corresponding sections of the deformed excised tissue. In both adult mouse and Yucatan minipig brains, cortical grey matter exhibited predominantly compressive stresses, while white matter exhibited strongly anisotropic tensile stresses. The direction of maximum tension in white matter generally aligns with axon orientation as observed with diffusion MRI in the minipig. These stress patterns (compressive in cortical grey matter, tensile along axons) are consistent with constrained cortical expansion and tension-induced axonal growth during brain development. These findings offer new insights into the biomechanical factors underlying brain morphogenesis, with implications for understanding neurodevelopmental disorders, brain injuries, and neurosurgical interventions.

bioengineering↗

bioRxiv2019

Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins.

A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enabled mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale integrated analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the large-scale mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types. Here we describe our analysis of 223 enhanced (eCLIP) datasets characterizing 150 RBPs in K562 and HepG2 cell lines, revealing a range of binding modalities, including highly resolved positioning around splicing signals and mRNA untranslated regions that associate with distinct RBP functions. Quantification of enrichment for repetitive and abundant multi-copy elements reveals 70% of RBPs have enrichment for non-mRNA element classes, enables identification of novel ribosomal RNA processing factors and sites and suggests that association with retrotransposable elements reflects multiple RBP mechanisms of action. Analysis of spliceosomal RBPs indicates that eCLIP resolves AQR association after intronic lariat formation (enabling identification of branch points with single-nucleotide resolution) and provides genome-wide validation for a branch point-based scanning model for 3 splice site recognition. Further, we show that eCLIP peak co-occurrences across RBPs enables the discovery of novel co-interacting RBPs. Finally, we present a protocol for visualization of RBP:RNA complexes in the eCLIP workflow using biotin and standard chemiluminescent visualization reagents, enabling simplified confirmation of ribonucleoprotein enrichment without radioactivity. This work illustrates the value of integrated analysis across eCLIP profiling of RBPs with widely distinct functions to reveal novel RNA biology. Further, our quantification of both mRNA and other element association will enable further research to identify novel roles of RBPs in regulating RNA processing.

genomics↗

bioRxiv2017

Dynamic patterns of cortical expansion during folding of the preterm human brain

During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data suggests that growth may vary in both space (by region on the cortical surface) and time. In this study, we propose a new method to estimate local growth from sequential cortical reconstructions. Using anatomically-constrained Multimodal Surface Matching (aMSM), we obtain accurate, physically-guided point correspondence between younger and older cortical reconstructions of the same individual. From each pair of surfaces, we calculate continuous, smooth maps of cortical expansion with unprecedented precision. By considering 30 preterm infants scanned 2-4 times during the period of rapid cortical expansion (28 to 38 weeks postmenstrual age), we observe significant regional differences in growth across the cortical surface that are consistent with patterns of active folding. Furthermore, these growth patterns shift over the course of development, with non-injured subjects following a highly consistent trajectory. This information provides a detailed picture of dynamic changes in cortical growth, connecting what is known about patterns of development at the microscopic (cellular) and macroscopic (folding) scales. Since our method provides specific growth maps for individual brains, we are also able to detect alterations due to injury. This fully-automated surface analysis, based on tools freely available to the brain mapping community, may also serve as a useful approach for future studies of abnormal growth due to genetic disorders, injury, or other environmental variables.\n\nSignificance StatementThe human brain exhibits complex folding patterns that emerge during the third trimester of fetal development. Minor folds are quasi-randomly shaped and distributed. Major folds, in contrast, are more conserved and form important landmarks. Disruption of cortical folding is associated with devastating disorders of cognition and emotion. Despite decades of study, the processes that produce normal and abnormal folding remain unresolved, although the relatively rapid tangential expansion of the cortex has emerged as a driving factor. Accurate and precise measurement of cortical growth patterns during the period of folding has remained elusive. Here, we illuminate the spatiotemporal dynamics of cortical expansion by analyzing MRI-derived surfaces of preterm infant brains, using a novel strain energy minimization approach.

neuroscience↗