Developmental biology is the study of how cells with specialized functions are derived from undifferentiated cells and how cells interact with each other and their environment to ultimately form tissues and organs. Members of the TGF-? superfamily are secreted signaling proteins that regulate many aspects of development and tissue homeostasis including growth, patterning, and cellular differentiation. Polymorphisms and mutations in genes that regulate Tgfb activity have been associated with pathology in the adult spine. Previously, we showed using genetically engineered mouse models that Tgfbr2 is required for development and maintenance of the intervertebral disc (IVD). Results published during the previous funding period suggest that Tgfb 1) inhibits the formation of vertebral cartilage to maintain the IVD boundary and 2) promotes differentiation of annulus fibrosus from sclerotome. The long-term objective of this study is to understand signals normally involved in IVD development so that in vitro processes that mimic normal development can be applied to tissue engineering strategies. Specific hypotheses based on published results and preliminary data obtained during the previous funding period will be tested in the following specific aims: #1 To test the roles of the transcription factors Erg and c-Maf in Tgfb-mediated regulation of IVD development. #2 To identify positive transcription factor regulators of IVD differentiation. #3 To test the hypothesis that Tgfb is sufficient to induce cell alignment and lamellar structure in undifferentiated mesenchymal cells grown on a PCL/Col1 blended scaffold. The experiments described here will characterize the earliest stages of IVD development and provide information necessary for future efforts to developmentally engineer IVD.
Developmental biology is the study of how cells with specialized functions are derived from undifferentiated cells to ultimately form mature tissues and organs. The term developmental engineering was recently coined to describe an approach to tissue engineering that attempts to mimic normal development. The experiments described here will characterize the earliest stages of IVD development and provide information necessary for future efforts to developmentally engineer IVD and provide relief to those suffering from damaged IVD.
|Alkhatib, Bashar; Ban, Ga I; Williams, Sade et al. (2018) IVD Development: Nucleus pulposus development and sclerotome specification. Curr Mol Biol Rep 4:132-141|
|Killion, Christy H; Mitchell, Elizabeth H; Duke, Corey G et al. (2017) Mechanical loading regulates organization of the actin cytoskeleton and column formation in postnatal growth plate. Mol Biol Cell 28:1862-1870|
|Peters, Sarah B; Wang, Ying; Serra, Rosa (2017) Tgfbr2 is required in osterix expressing cells for postnatal skeletal development. Bone 97:54-64|
|Cox, Megan K; Appelboom, Brittany L; Ban, Ga I et al. (2014) Erg cooperates with TGF-? to control mesenchymal differentiation. Exp Cell Res 328:410-8|
|Wang, Ying; Cox, Megan K; Coricor, George et al. (2013) Inactivation of Tgfbr2 in Osterix-Cre expressing dental mesenchyme disrupts molar root formation. Dev Biol 382:27-37|
|Chang, Ching-Fang; Serra, Rosa (2013) Ift88 regulates Hedgehog signaling, Sfrp5 expression, and ?-catenin activity in post-natal growth plate. J Orthop Res 31:350-6|
|Wang, Ying; Serra, Rosa (2012) PDGF mediates TGFýý-induced migration during development of the spinous process. Dev Biol 365:110-7|
|Ramaswamy, Girish; Sohn, Philip; Eberhardt, Alan et al. (2012) Altered responsiveness to TGF-ýý results in reduced Papss2 expression and alterations in the biomechanical properties of mouse articular cartilage. Arthritis Res Ther 14:R49|
|Chang, C-F; Ramaswamy, G; Serra, R (2012) Depletion of primary cilia in articular chondrocytes results in reduced Gli3 repressor to activator ratio, increased Hedgehog signaling, and symptoms of early osteoarthritis. Osteoarthritis Cartilage 20:152-61|
|Sohn, Philip; Cox, Megan; Chen, Dongquan et al. (2010) Molecular profiling of the developing mouse axial skeleton: a role for Tgfbr2 in the development of the intervertebral disc. BMC Dev Biol 10:29|
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