Browsing by Author "Jacobson, Kathryn R."

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    3D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney Development
    (Wolters Kluwer, 2021) Lipp, Sarah N.; Jacobson, Kathryn R.; Hains, David S.; Schwarderer, Andrew L.; Calve, Sarah; Pediatrics, School of Medicine
    ESKD is increasing in incidence and a limited number of organs are available for transplantation. Therefore, researchers have focused on understanding how cellular signaling influences kidney development to expand strategies to rebuild a kidney. However, the extracellular matrix (ECM), another critical component that biomechanically regulates nephrogenesis, has been largely neglected. Proteomics and 3D imaging of the murine kidney resolved previously undescribed dynamics of the interstitial matrix in the cortex and corticomedullary junction during development. Combined with cells and growth factors, scaffolds modeled after the composition and organization of the developmental ECM have the potential to improve engineered models of the kidney.
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    Extracellular matrix protein composition dynamically changes during murine forelimb development
    (Elsevier, 2024-01-09) Jacobson, Kathryn R.; Saleh, Aya M.; Lipp, Sarah N.; Tian, Chengzhe; Watson, Audrey R.; Luetkemeyer, Callan M.; Ocken, Alexander R.; Spencer, Sabrina L.; Kinzer-Ursem, Tamara L.; Calve, Sarah; Medicine, School of Medicine
    The extracellular matrix (ECM) is an integral part of multicellular organisms, connecting different cell layers and tissue types. During morphogenesis and growth, tissues undergo substantial reorganization. While it is intuitive that the ECM remodels in concert, little is known regarding how matrix composition and organization change during development. Here, we quantified ECM protein dynamics in the murine forelimb during appendicular musculoskeletal morphogenesis (embryonic days 11.5-14.5) using tissue fractionation, bioorthogonal non-canonical amino acid tagging, and mass spectrometry. Our analyses indicated that ECM protein (matrisome) composition in the embryonic forelimb changed as a function of development and growth, was distinct from other developing organs (brain), and was altered in a model of disease (osteogenesis imperfecta murine). Additionally, the tissue distribution for select matrisome was assessed via immunohistochemistry in the wild-type embryonic and postnatal musculoskeletal system. This resource will guide future research investigating the role of the matrisome during complex tissue development.
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    Mechanical loading is required for initiation of extracellular matrix deposition at the developing murine myotendinous junction
    (Elsevier, 2023) Lipp, Sarah N.; Jacobson, Kathryn R.; Colling, Haley A.; Tuttle, Tyler G.; Miles, Dalton T.; McCreery, Kaitlin P.; Calve, Sarah; Medicine, School of Medicine
    The myotendinous junction (MTJ) contributes to the generation of motion by connecting muscle to tendon. At the adult MTJ, a specialized extracellular matrix (ECM) is thought to contribute to the mechanical integrity of the muscle-tendon interface, but the factors that influence MTJ formation during mammalian development are unclear. Here, we combined 3D imaging and proteomics with murine models in which muscle contractility and patterning are disrupted to resolve morphological and compositional changes in the ECM during MTJ development. We found that MTJ-specific ECM deposition can be initiated via static loading due to growth; however, it required cyclic loading to develop a mature morphology. Furthermore, the MTJ can mature without the tendon terminating into cartilage. Based on these results, we describe a model wherein MTJ development depends on mechanical loading but not insertion into an enthesis.