Biology subjects

Fischer, S.

Publications and source records attributed to Fischer, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Comparative Analysis of Transposable Elements in Hermetia illucens

BackgroundThe black soldier fly (Hermetia illucens) is an emerging model for bioconversion and industrial rearing. Its genome is highly repetitive, yet the contribution of transposable elements (TEs) to population divergence and demographic processes. The sampled populations represent a gradient of demographic histories, including wild and near-wild North American populations, and domesticated European strains with shared industrial origins. Difference in TE composition may influence genome structure, regulatory variation, and evolutionary responses to captive environments. ResultsA comparative analysis of the repetitive landscape was done for four H. illucens genomes, one of which is a wild-caught specimen. Total repeat content was high across all assemblies (67.6% to 70.8%) and dominated by LINE elements. Class-level TE diversity was nearly identical among genomes, but multiple DNA transposon families showed distinct lineage-specific differences. Large families including Maverick and Academ were generally depleted relative to the wild sample. Divergence profiles revealed patterns consistent with recent turnover in several families. Family level turnover, rather than class level change, accounted for the most difference among the genomes. TE-associated structural variants (TESVs) were also not uniformly distributed. Most chromosomes showed mid-chromosome enrichment, and a pronounced TESV peak on chromosome 5 overlapped a histone rich region containing many unclassified repeats. Use of a repeat library derived from multiple genomes increased the number of detected TESVs and improved classification within complex regions, demonstrating that multi-genome libraries enhance annotation accuracy compared to single reference-based models. ConclusionsMultiple DNA transposon families show evidence of recent or lineage-specific amplification in H. illucens, suggesting that TE amplification contributes to genome variation during demography-associated TE turnover. The multi-genome-based library improved TE detection and classification, providing a proof of concept that even a small lineage-inclusive repeat library enhances annotation accuracy and capture TE diversity missed by single-reference approaches. Together, these findings demonstrate that TE family turnover plays a significant role in shaping genome architecture and adaptation in this species.

genomics↗

bioRxiv2026

Adolescent Astrocyte Dysregulation Impairs Prefrontal Interneuron Maturation and Adult Cognition

The prefrontal cortex (PFC), a brain region critical for executive and cognitive functions, is characterized by its protracted maturation extending through adolescence until early adulthood. During adolescence, the PFC undergoes substantial rearrangements, creating a window of heightened plasticity allowing experience-dependent refinement of neural networks. While this extended plasticity supports the development of higher-order cognitive functions, it also confers increased vulnerability to environmental and biological perturbations that can disrupt circuit development and contribute to cognitive and behavioral impairments relevant to psychiatric disorders. Astrocytes are central regulators of brain homeostasis and actively participate in developmental processes that shape postnatal brain maturation. Although astrocyte dysfunction has been increasingly linked to psychiatric pathophysiology, it remains unknown whether aberrant astrocyte activity can directly influence PFC development and cognitive maturation. Here, using selective modulation of astrocyte activity during defined developmental windows in the PFC, we show that abnormal astrocyte activity during adolescence induces transient synaptic loss through enhanced microglial phagocytosis, produces long-lasting alterations in fast-spiking parvalbumin (PV) interneurons, and results in persistent deficits in PFC-dependent behaviors. Together, these findings provide causal evidence that disrupted astrocyte function during adolescent PFC maturation can lead to persistent neuronal and cognitive deficits with relevance to major psychiatric disorders.

neuroscience↗

bioRxiv2026

Engineering physically optimized T cells for increased sampling of complex tumor microenvironments

Pancreatic ductal adenocarcinoma (PDA) remains highly lethal, in part, because its dense fibroinflammatory stroma restricts therapy distribution, including adoptive T cell immunotherapies where direct interactions between T and carcinoma cells are essential for effective therapy. While T cell function must be maintained once effector-target engagement occurs, without inducing co-localization subsequent cytotoxic function steps cannot be undertaken. We therefore developed a strategy to "physically optimize" T cells to more effectively sample complex tumor volumes. Informed by pharmacologic perturbations and mathematical modeling we shifted T cell phenotype through expression of constitutively activated RhoA to increase cortical contractility, activation, migration, and sampling in PDA, while showing decreases in exhaustion markers. In CAR T cells this results in more efficient targeting through decreased sampling time and increased engagement with carcinoma cells, consistent with modeling predictions. This significantly increases T cell infiltration and distribution in PDA, resulting in improved tumor control in vivo, suggesting that this is an effective strategy to overcome stromal constraints, improve tumor engagement, and enhance the therapeutic performance of engineered T cell therapies in solid tumors.

bioengineering↗

bioRxiv2025

Discovery of a Novel Chimeric Transposase-Transposon System for Advanced Genome Engineering

Transposases revolutionized the field of genetic engineering, yet the scarcity of functional systems remains a challenge. In response, we conducted a metagenomic screening and identified a novel transposase system from Acyrthosiphon pisum. Through systematic optimization, we enhanced nuclear localization, transposon composition, and created a hyperactive transposase variant to boost transposition efficiency. Intriguingly, the combined application of the newly discovered transposase with inverted terminal repeat sequences from a related pea aphid species, Aphis craccivora, further enhanced transposition activity, resulting in the first chimeric transposase system reported so far. We investigated the genomic integration events following transposition in mammalian cells, to understand the underlying mechanisms and optimize the efficiency of transgene integration. This optimized system can expedite the generation of recombinant protein producing CHO cell lines, even surpassing the hyperactive piggyBac system with regards to cell specific productivity. These findings introduce a significant addition to the field of semi-targeted transgene integration technologies, offering substantial potential for enhancing biologics manufacturing.

bioengineering↗

bioRxiv2025

Loss of ADAMTS9 results in Nephronophthisis like polycystic kidneys by disrupting ciliogenesis and ECM dynamics

ADAMTS9 mutations cause the ciliopathies nephronophthisis and Joubert syndrome. Here we show that deletion of ADAMTS9 in the proximal nephron leads to polycystic kidney development in mice. In males, Adamts9 deletion cause kidneys to become highly cystic but remain small without undergoing enlargement, causing early postnatal lethality. Female mice on the other hand, develop cystic kidneys but progress slowly. ADAMTS9 deletion disrupted ciliogenesis by the loss of ciliary transition zone (TZ) protein TMEM67 cleavage, leading to loss of the MKS/B9 module - a key component of the ciliary gate. Functional analysis of all eight ciliopathy patient variants of ADAMTS9 identified to date, showed TMEM67 C-terminus failed to localize to the transition zone, thus disrupting a key regulatory mechanism in patient renal ciliogenesis. Modeling ADAMTS9-mediated TMEM67 cleavage utilizing our novel TMEM67-cleavage deficient mice revealed loss of TZ formation but not elevated canonical Wnt signaling as the underlying mechanism driving cystogenesis. We show that Adamts9 deletion leads to comparatively intense interstitial collagen deposition, which likely restricts kidney enlargement resulting in the characteristically small kidney phenotype in nephronophthisis and increased immune response. By comparative analysis of four interconnected polycystic kidney models in addition to Pkd1 and Pkd2 deleted kidneys, we identify differential collagen homeostasis is the principle determining factor deciphering cystic kidney size and type.

cell biology↗

bioRxiv2025

Genetic incorporation of diverse non-canonical amino acids for histidine substitution

Using genetic code expansion, canonical amino acid residues can be site-specifically substituted by non-canonical amino acids (ncAAs) with modified chemical properties. This technique has enabled detailed enzymatic studies, the design of enzymes that catalyze novel reactions, and the engineering of enzymes with improved function. In proteins, histidine can play versatile roles in catalysis including as an acid, a base, a nucleophile, and a coordinating ligand to a catalytic metal. However, the current scope of histidine-like ncAAs that can be incorporated is limited. Herein, we develop a toolkit consisting of nine new aminoacyl-tRNA synthetase/tRNA pairs for the site-specific genetic encoding of an expanded set of 12 new histidine-like ncAAs. The 12 ncAAs feature broadly tuned nitrogen pKaH, alternative heterocycles, and varying substitution patterns. We profile the substrate specificity of the developed aaRS/tRNA pairs and uncover many mutually orthogonal substrate specificities, which we validate for six combinations of dual encoded histidine-like ncAAs. We expect that the tools presented herein will be broadly applicable to study histidine residues in catalysis and to tune the properties of histidine residues for enzyme engineering and design.

synthetic biology↗

bioRxiv2025

Bioactive Enhanced Adjuvant Chemokine Oligonucleotide Nanoparticles (BEACONs) for Mucosal Vaccination Against Genital Herpes

Genital herpes, caused by herpes simplex virus-2 (HSV-2), remains a prevalent sexually transmitted infection with no available vaccine. Effective local immunity--including tissue-resident memory T cells (TRMs) and luminal antibodies--provides immediate viral control. Here, we developed Bioactive Enhanced Adjuvant Chemokine Oligonucleotide Nanoparticles (BEACON) formed via electrostatic interactions between CpG oligodeoxynucleotides (CpG ODN) and the chemokine CXCL9. This adjuvant enhances antigen-presenting cell engagement and innate immune signaling, promotes CD8+ T cell recruitment, and reduces local neutrophilic inflammation relative to CpG ODN. Co-administered vaginally with HSV-2 glycoproteins following intramuscular priming, BEACON improved protection against HSV-2 by increasing local CD8+ TRM populations and mucosal IgG and IgA responses. Vaccine-mediated protection required local delivery of both antigen and adjuvant, and was significantly reduced by CD8+ T cell or B cell depletion. These findings highlight the potential of engineered mucosal adjuvants for vaccines targeting genital herpes and other sexually transmitted infections. One-sentence summaryWe developed BEACON, a mucosal adjuvant that elicits protective immunity against genital herpes simplex virus 2 infection in mice.

immunology↗

bioRxiv2025

Nutritional state and predator exposure jointly mediate stress resilience and behavioural flexibility

Behavioral flexibility plays an important role in adaptation to changing environments within an individuals lifetime. Stress resilience influences flexibility, as short-term stress can enhance attention and memory, while prolonged stress may impair cognitive function. Nutritional state also plays a role, with overweight individuals often suffering greater consequences of chronic stress. The allostatic load model predicts that individuals under prolonged stress remain in a chronically activated state, potentially reducing flexibility. Using a cichlid, we manipulated body condition and exposed individuals to occasional or frequent predator presentations. We then assessed stress responses and behavioral flexibility via a reversal learning test. Contrary to predictions, fish in a high nutritional state - but not overweight - that were frequently exposed to predators recovered rapidly from stress and exhibited enhanced flexibility. Our results provide direct evidence that nutritional state interacts with behavioral flexibility, revealing the costs of coping with repeated stressors. We highlight a link between brief stress responses, characterized by rapid cortisol recovery, and behavioral flexibility. This association only emerged in well-nourished individuals facing frequent stressors, suggesting energy reserves buffer the costs of repeated stress. Thus, resilience benefits behavioral flexibility, while it is energetically costly, as a reduced diet hindered adaptation to environmental change.

animal behavior and cognition↗

bioRxiv2025

Development of DARPin T cell engagers for specific targeting of tumor-associated HLA/peptide complexes

The compromise between affinity and specificity in TCR-dependent targeting of HLA-restricted tumor-associated antigens presents a significant challenge in developing efficacious immunotherapies. As such, T cell engagers which circumvent these limitations are of particular interest. We have established a process to generate bispecific Designed Ankyrin Repeat Proteins (DARPins) that simultaneously target HLA-I molecules in complex with tumor-associated peptides and CD3{varepsilon}. High-affinity HLA-A*0201/NY-ESO1157-165-specific DARPins were isolated after only four rounds of in-vitro selection from naive DARPin libraries. Combining HLA-A*0201/NY-ESO1157-165-specific DARPins with a CD3{varepsilon}-specific DARPin created potent T cell engagers which elicited CD8+ T cell activation towards tumor targets with high peptide specificity, as confirmed by X-scanning mutagenesis and functional killing assays. The cryo-EM structure of a ternary DARPin/HLA-A*0201/NY-ESO1157-165 complex revealed a rigid and concave DARPin surface that binds to the entire length of the peptide-binding cleft, contacting both -helices and the peptide. The present results unveil promising immuno-oncotherapeutic approaches with the possibility of rapidly developing DARPins with high affinity and specificity to HLA/peptide targets that can be readily combined with a new generation of anti-CD3{varepsilon}-specific DARPins.

synthetic biology↗

bioRxiv2025

VESNA: An Open-Source Tool for Automated 3D Vessel Segmentation and Network Analysis

BackgroundVasculature is an essential part of all tissues and organs and is involved in a wide range of different diseases. However, available software for blood vessel image analysis is often limited: Some only process two-dimensional data, others lack batch processing, putting a time burden on the user, while still others require tightly defined culturing methods and experimental conditions. This highlights the need for a software that has the ability to batch process three-dimensional image data and requires few and simple experimental preparation steps. ResultsWe present VESNA, a Fiji (ImageJ) macro for automated segmentation and skeletonization of three-dimensional fluorescence images, enabling quantitative vascular network analysis. It requires only basic experimental preparation, making it highly adaptable to a wide range of possible applications across experimental goals and different tissue culturing methods. The macros potential is demonstrated on a range of different image data sets, from organoids with varying sizes, network complexities, and growth conditions to expanding to other 3D tissue culturing methods with an example of hydrogel-based cultures. ConclusionsWith its ability to process large amounts of 3D image data and its flexibility across experimental conditions, VESNA fulfills previously unmet needs in image processing of vascular structures and can be a valuable tool for a variety of experimental setups around three-dimensional vasculature, such as drug screening, research in tissue development and disease mechanisms.

bioinformatics↗

bioRxiv2025

Hydrophobic tuning with non-canonical amino acids in a copper metalloenzyme

Hydrophobicity controls many aspects of protein and enzyme function. Although hydrophobic tuning can be achieved to a limited extent with canonical amino acids, the incorporation of non-canonical amino acids (ncAAs) further extends this ability to enable new and improved functionality. Herein, we engineer an aminoacyl-tRNA synthetase/tRNA pair for the site-specific genetic encoding of a set of bulky, hydrophobic amino acids, namely cyclopentylalanine, cyclohexylalanine, and cycloheptylalanine. With the resulting orthogonal translations systems, we demonstrate the utility of ncAA-based hydrophobic tuning to engineer a bacterial laccase, which is both a classical metalloenzyme and a high-value catalyst for industrial processes. The resulting mutations conveyed significant improvements in catalytic activity, particularly kcat and total turnover number. The redox potential and structure-function relationships were examined to elucidate the source of this improved functionality. We envision that these tools for hydrophobic tuning will be highly valuable for general enzyme engineering and also in other fields, including peptide chemistry.

synthetic biology↗

bioRxiv2025

The MYCN/Aurora-A complex is a cyclin activating kinase for CDK12

Deregulated MYCN is a driver of aggressive pediatric and adult neuroendocrine tumors, but critical oncogenic processes downstream of MYCN remain poorly defined. In neuroblastoma, MYCN interacts with and activates the Aurora-A kinase. Here we show that Aurora-A is a CDK-activating kinase for CDK12 by phosphorylating T893 in the T-loop, thereby enhancing its kinase activity. Aurora-A-dependent activation of CDK12 controls phosphorylation of T4 of RNA polymerase and recruits transcription termination complexes, thereby preventing transcription-replication conflicts. Enhanced crosslinking and immunoprecipitation sequencing reveals that Aurora-A associates with splice sites on nascent RNA. RNA-bound Aurora-A is catalytically inactive. MYCN competes with RNA for binding to Aurora-A and displaces Aurora-A from RNA in cells, promoting its CDK12 kinase activity. Combining Aurora-A and CDK12 inhibition potently suppresses the growth of MYCN-amplified neuroblastoma cells and patient-derived xenografts. Our data demonstrate that an Aurora-A/CDK12-dependent transcription termination pathway is a critical and targetable dependency of MYCN-driven tumors.

cancer biology↗

bioRxiv2025

Ontogeny drives stage-specific effects of a Gata1 mutation

The biography of an organism, including, for instance, its genetic background and exposure to environmental influences, determines the penetrance and expressivity of monogenic diseases between individuals. This also applies at the single-cell level. Interestingly, mature blood and immune cells originate from anatomically and temporally distinct stem and progenitor populations at different stages of development. Here we show that the ontogeny or progenitor origin of megakaryocytes determines their developmental trajectory at the cellular and transcriptional level. As a result, a mutation in the key transcription factor Gata1 dysregulates megakaryopoiesis in an ontogeny-specific manner causing a stage-specific disorder. Particularly, only early extraembryonic hematopoietic progenitors drive blast-like cell development leading to a transient accumulation of megakaryocytes in the fetus but not in the adult. Therefore, pediatric blood disorders may differ functionally from adult diseases due to changing progenitor sources of mature blood and immune cells throughout development. HighlightsO_LIFetal and adult megakaryopoiesis pass through distinct immunophenotypic stages C_LIO_LIOntogeny of megakaryocytes dictates their unique transcriptional trajectory C_LIO_LIProgenitor origin rather than the differentiation pathway determines the effect of mutant Gata1 C_LIO_LIBlock in maturation at the progenitor level causes the accumulation of yolk sac-derived megakaryocytes in the presence of mutant Gata1 C_LIO_LIMutant Gata1 drives blast cell formation exclusively in yolk sac-derived lineages C_LI

developmental biology↗

bioRxiv2024

Element partitioning, element localisation and transcriptome responses of date palms exposed to NaCl

Date palm (Phoenix dactylifera L.) is an economically important fruit crop in many (semi)arid regions. Large intra-species variation in susceptibility to NaCl has been reported. Controlled experiments were conducted to evaluate sodium (Na) and chlorine (Cl) partitioning in two-year old plants of six date palm varieties and to determine tissue location of Na and Cl and transcriptome responses to NaCl of two varieties. The largest Na concentrations were found in secondary roots, especially under NaCl treatment. By contrast, only small differences in within-plant partitioning of Cl were observed with less differences between varieties than for Na. Variety Sultana had the largest Na translocation factor. The variety Khalas exhibited better restriction of Na mobility, which may be a consequence of Na hotspots in roots, presumably immobilising Na in roots, which were absent in Sultana. In the root, shoot base and lower part of leaves, Cl accumulated in fibre bands and sclerenchyma sheaths of vascular bundles. RNAseq analysis revealed that Sultana and Khalas respond very differently to NaCl: Khalas modified expression of NaCl-specific genes in both roots and leaves, while Sultana responded manly in leaves. Gene ontology analysis showed that the expression changes for genes linked with photosynthesis and carbohydrate metabolism predominated as a response to NaCl. In Khalas, differentially expressed genes encoding for metal transporters and those reported to be involved in heat, salt and osmotic stress response were found. Large variability in Na and Cl accumulation in different date palm varieties may have practical agronomical consequences.

plant biology↗

bioRxiv2024

Multiple within species comparisons show Tanganyikan cichlid fish have larger brains in less structurally complex habitats

Many studies have found a link between higher habitat structural complexity and increased relative brain size in vertebrates. Here we explore this relationship in a multi-species comparison, comparing ten species of wild cichlids that differ in their social and territorial behaviour, but which occur across four ecologically similar but structurally diverse rocky habitats. This design allows us to perform repeated intra-specific comparisons, avoiding confounds associated with comparisons across species boundaries. We sampled 147 fish, analysing brain size and architecture while controlling for body mass and species-specific variability and compared this with habitat complexity, quantified using underwater video and three-dimensional reconstructions. Our results challenge the Clever Foraging Hypothesis (CFH), which posits that greater habitat complexity correlates with larger brain sizes. Contrary to CFH, fish from the least complex habitat had significantly larger brains. Additionally, brain architecture analysis indicated a significant enlargement of the cerebellum in fish from less complex habitats, whereas the hypothalamus showed a non-significant negative trend. Taken together, these results indicate that lower habitat complexity may impose higher cognitive demands on spatial memory and navigation due to limited refuges and increased predation risk. This study highlights the need to reconsider the assumed linear positive relationship between environmental complexity and brain development, suggesting that simpler environments might also impose significant cognitive and ecological challenges that drive brain evolution. Our findings underscore the importance of considering intra-species variability and the specific ecological and cognitive demands of different habitats in studies of brain evolution.

evolutionary biology↗

bioRxiv2024

Two functional forms of the Meckel-Gruber syndrome protein TMEM67 generated by proteolytic cleavage by ADAMTS9 mediate Wnt signaling and ciliogenesis

TMEM67 mutations are the major cause of Meckel-Gruber syndrome. TMEM67 is involved in both ciliary transition zone assembly, and non-canonical Wnt signaling mediated by its extracellular domain. How TMEM67 performs these two separate functions is not known. We identify a novel cleavage motif in the extracellular domain of TMEM67 cleaved by the extracellular matrix metalloproteinase ADAMTS9. This cleavage regulates the abundance of two functional forms: A C-terminal portion which localizes to the ciliary transition zone regulating ciliogenesis, and a non- cleaved form which regulates Wnt signaling. By characterizing three TMEM67 ciliopathy patient variants within the cleavage motif utilizing mammalian cell culture and C. elegans, we show the cleavage motif is essential for cilia structure and function, highlighting its clinical significance. We generated a novel non-cleavable TMEM67 mouse model which develop severe ciliopathies phenocopying Tmem67-/- mice, but in contrast, undergo normal Wnt signaling, substantiating the existence of two functional forms of TMEM67.

cell biology↗

bioRxiv2024

Bacterial motility depends on a critical flagellum length and energy-optimised assembly

The flagellum is the most complex macromolecular structure known in bacteria and comprised of around two dozen distinct proteins. The main building block of the long, external flagellar filament, flagellin, is secreted through the flagellar type-III secretion system at a remarkable rate of several tens of thousands amino acids per second, significantly surpassing the rates achieved by other pore-based protein secretion systems. The evolutionary implications and potential benefits of this high secretion rate for flagellum assembly and function, however, have remained elusive. In this study, we provide both experimental and theoretical evidence that the flagellar secretion rate has been evolutionarily optimized to facilitate rapid and efficient construction of a functional flagellum. By synchronizing flagellar assembly, we found that a minimal filament length of 2.5 {micro}m was required for swimming motility. Biophysical modelling revealed that this minimal filament length threshold resulted from an elasto-hydrodynamic instability of the whole swimming cell, dependent on the filament length. Furthermore, we developed a stepwise filament labeling method combined with electron microscopy visualization to validate predicted flagellin secretion rates of up to 10,000 amino acids per second. A biophysical model of flagellum growth demonstrates that the observed high flagellin secretion rate efficiently balances filament elongation and energy consumption, thereby enabling motility in the shortest amount of time. Taken together, these insights underscore the evolutionary pressures that have shaped the development and optimization of the flagellum and type-III secretion system, illuminating the intricate interplay between functionality and efficiency in assembly of large macromolecular structures. Significance statementOur study demonstrates how protein secretion of the bacterial flagellum is finely tuned to optimize filament assembly rate and flagellum function while minimizing energy consumption. By measuring flagellar filament lengths and bacterial swimming after initiation of flag-ellum assembly, we were able to establish the minimal filament length necessary for swimming motility, which we rationalized physically as resulting from an elasto-hydrodynamic instability of the swimming cell. Our bio-physical model of flagellum growth further illustrates how the physiological flagellin secretion rate is optimized to maximize filament elongation while conserving energy. These findings illuminate the evolutionary pressures that have shaped the function of the bacterial flagellum and type-III secretion system, driving improvements in bacterial motility and overall fitness.

microbiology↗

bioRxiv2024

Distinct Gene Regulatory Dynamics Drive Skeletogenic Cell Fate Convergence During Vertebrate Embryogenesis

Cell type repertoires have expanded extensively in metazoan animals, with some clade-specific cells being paramount to their evolutionary success. A prime example are the skeletogenic cells of vertebrates that form the basis of their developing endoskeletons. Depending on anatomical location, these cells originate from three different embryonic precursor lineages - the neural crest, the somites, and the lateral plate mesoderm - yet they converge developmentally towards similar cellular phenotypes. Furthermore, these lineages have gained skeletogenic competency at distinct timepoints during vertebrate evolution, thus questioning to what extent different parts of the vertebrate skeleton rely on truly homologous cell types. Here, we investigate how lineage-specific molecular properties of the three precursor pools are integrated at the gene regulatory level, to allow for phenotypic convergence towards a skeletogenic cell fate. Using single-cell transcriptomics and chromatin accessibility profiling along the precursor-to-skeletogenic cell continuum, we examine the gene regulatory dynamics associated with this cell fate convergence. We find that distinct transcription factor profiles are inherited from the three precursor states, and that lineage-specific enhancer elements integrate these different inputs at the cis-regulatory level, to execute a core skeletogenic program. We propose a lineage-specific gene regulatory logic for skeletogenic convergence from three embryonic precursor pools. Early skeletal cells in different body parts thus share only a partial deep homology. This regulatory uncoupling may render them amenable to individualized selection, to help to define distinct morphologies and biomaterial properties in the different parts of the vertebrate skeleton.

developmental biology↗