Biology subjects

Young, N. M.

Publications and source records attributed to Young, N. M..

4 recordsLinked to original sources

bioRxiv2026

Heterochronic Uncoupling of Brain and Face Morphogenesis Drives Premature Fusion in Ciliary Transition Zone Mutants

Normal facial development is highly coordinated with embryonic brain expansion, suggesting the forebrain acts as a physical scaffold dictating the spatial timing of facial prominence apposition and fusion. To test this idea, we compared B9d1 ciliary transition zone mutants, which exhibit altered Hedgehog signaling and premature facial fusion, to a normal murine developmental morphospace. At e11.5, mutant brains are significantly reduced in size, yet intrinsic facial prominence size remains largely normal. Projecting e11.5 and e12.5 mutants into the normal morphospace reveals a severe heterochronic uncoupling: the delayed, narrowed neurocranium mechanically forces normal-sized facial prominences into premature convergence. These results indicate that when brain growth slows, facial prominences initiate contact earlier in restricted spatial bounds. Conversely, this model predicts that an accelerated, expanded brain may act as a physical wedge, increasing the likelihood of cleft lip. By mathematically modeling these structural dependencies, we propose that palatogenesis operates on a continuous phenotypic spectrum, where premature fusion and cleft lip represent alternative physical outcomes conditioned on the underlying brain developmental trajectory.

developmental biology↗

bioRxiv2026

Navigating the window: structural bottlenecks in avian craniofacial integration revealed by the ontogenetic patterning of shape variance

Background: Successful palatal morphogenesis requires the precise spatiotemporal choreography of independent facial prominences. Our previous macroevolutionary analyses identified a convergence in amniote facial growth at primary palatal fusion, associated with reduced shape variability. We hypothesize that this constraint operates within individual species, representing a shared structural bottleneck where brain growth acts as a critical morphogenetic co-factor. To test this idea, we analyzed high-resolution 3D micro-CT images of embryonic chickens (Gallus gallus, N=217) spanning primary palatogenesis. Utilizing 3D geometric morphometrics (3DGM), we quantified a continuous "developmental morphospace" integrating the face and brain. Results: Facial shape follows a highly nonlinear developmental trajectory. Using a continuous sliding-window analysis, we demonstrate that local morphological disparity undergoes a significant system-wide collapse coinciding with primary palatal fusion. Partial Least Squares (PLS) confirms this morphospace pivot is tightly coordinated with neurocranial development. Post-fusion, the modules uncouple: facial allometry switches from convergent to divergent projecting growth, while the brain undergoes spatial encapsulation, subsequently flatlining its morphological disparity. Conclusions: Craniofacial morphogenesis can be described in terms of a tightly regulated biphasic developmental hourglass. The physical tethering of facial prominences creates a brief structurally constrained "shape window" essential for successful fusion. Deviations from this bottleneck, whether driven by altered prominence trajectories, increased local variance, or disruptions to the underlying forebrain landscape, push embryos into unoccupied morphospace, providing a unified mechanical and predictive framework for the spatiotemporal origins of non-syndromic cleft lip.

developmental biology↗

bioRxiv2022

The Children's Brain Tumor Network (CBTN) - Accelerating Research in Pediatric Central Nervous System Tumors through Collaboration and Open Science

Pediatric brain tumors are the leading cause of cancer-related death in children in the United States and contribute a disproportionate number of potential years of life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary cancers. The Childrens Brain Tumor Network (CBTN) is a multi-institutional international clinical research consortium created to advance therapeutic development through the collection and rapid distribution of biospecimens and data via open-science research platforms for real-time access and use by the global research community. The CBTNs 32 member institutions utilize a shared regulatory governance architecture at the Childrens Hospital of Philadelphia to accelerate and maximize the use of biospecimens and data. As of August 2022, CBTN has enrolled over 4,700 subjects, over 1,500 parents, and collected over 65,000 biospecimen aliquots for research. Additionally, over 80 preclinical models have been developed from collected tumors. Multi-omic data for over 1,000 tumors and germline material is currently available with data generation for > 5,000 samples underway. To our knowledge, CBTN provides the largest open-access pediatric brain tumor multi-omic dataset annotated with longitudinal clinical and outcome data, imaging, associated biospecimens, child-parent genomic pedigrees, and in vivo and in vitro preclinical models. Empowered by NIH-supported platforms such as the Kids First Data Resource and the Childhood Cancer Data Initiative, the CBTN continues to expand the resources needed for scientists to accelerate translational impact for improved outcomes and quality of life for children with brain and spinal cord tumors.

cancer biology↗

bioRxiv2021

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↗