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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR053860-07
Application #
8629691
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Tyree, Bernadette
Project Start
2006-07-01
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
7
Fiscal Year
2014
Total Cost
$312,375
Indirect Cost
$99,875
Name
University of Alabama Birmingham
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294