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NIH grant 1K99AR087986-01: Melanoblast migration as a new paradigm for deciphering the mechanisms of basement membrane crossing
Institute: {'code': 'AR', 'abbreviation': 'NIAMS', 'name': 'National Institute of Arthritis and Musculoskeletal and Skin Diseases', 'admin_org_id': '12500006', 'admin_funding_url': ''}. PI: Rebecca Ann Jones. Award: $109987.
Start: 2026-09-11T00:00:00.
Project summary
Migration of cells through different tissue environments is essential to many biological processes including
organogenesis, wound healing and immune function. Epithelial and stromal tissue compartments are
fundamentally different, and cells adapt by using remarkably distinct modes of migration, whilst still retaining
their identity and ability to migrate. The influence of the environment on cellular function has been studied
primarily in vitro, which whilst informative, does not reflect the complex physiology of living tissues. An ongoing
challenge is to more accurately reflect the in vivo environment, particularly given that cell migration is linked to
several pathological events, including vascular disease, chronic inflammatory disease and cancer metastasis.
During mouse embryonic development, immature melanocytes (melanoblasts) first migrate through the stroma
(dermis) before crossing into the epithelium (epidermis). Critically, to transit between these compartments,
melanoblasts have to cross a basement membrane (BM), a poorly understood cellular phenomenon with
significant implications for our understanding of immune cell infiltration and cancer metastasis. It is known that
cancer cells co-opt developmental gene programs controlling migration and invasion, and a great deal can
therefore be learned about human disease by studying these fundamental developmental events. Dr Jones’
proposal will uncover the cellular and molecular mechanisms underpinning how cells migrate in and move
between tissue compartments in vivo, using migration of melanoblasts as a model. Dr Jones’ development of
the mTurq2-Col4a1 mouse model in which all BMs are labelled, together with advanced live-imaging techniques,
has allowed BM transit by melanoblasts to be visualized live, in vivo, for the first time. Aim 1 will use these live-
imaging methods to characterize how, where and when cells cross the BM in vivo, whilst Aim 2 will use scRNA-
seq and spatial transcriptomics to identify and validate the gene signatures associated with melanoblasts in both
stromal and epithelial compartments and those transiting between, across the BM. These data will then be
combined, generating a high-resolution transcriptional map of melanoblast migration. Aim 3 will functionally
validate promising BM crossing candidate genes, revealing their mechanistic roles in vivo, and providing
foundational data to identify novel biomarkers of metastasis. Dr Jones will then expand this work to uncover
compartment-specific regulation of other fundamental cell migratory behaviors in vivo, including how the
cytoskeleton regulates transitions between different modes of cell migration. Training in bioinformatics, next-
generation sequencing and data integration pipelines will ensure Dr Jones’ success. Princeton University
provides an ideal setting for this proposal at the intersection of quantitative live-imaging and transcriptomics. Dr
Jones will be supported throughout her transition to an independent academic position, where she will use the
physiologically relevant model of melanoblast migration to transform our understanding of cell migration in vivo.document fetched 2026-09-20 02:42