My long-term objective is to define the cellular and molecular basis of tissue interactions that control aspects of craniofacial development. Understanding how development of the brain and face normally occurs will afford a better understand of how malformations arise within these tissues. From these insights, we will be able to generate therapeutic approaches to treat craniofacial malformation sequences. My multidisciplinary training has focused on development of the craniofacial musculoskeletal system using biochemical, molecular, cellular, histological, and morphological approaches. The work proposed in this application stems from this training, and forms the basis for an R01 application at a later date. The skeleton of the midface is derived from neural crest cells located in the frontonasal and maxillary processes, and requires signaling interactions with neighboring tissues for proper patterning. I hypothesize that molecular interactions occurring between the brain and cells in the frontonasal process establish regional characteristics within the neural crest and facial ectoderm and that some of these interactions are mediated by Bone morphogenetic proteins (Bmps). To test this, I will use retroviral gene delivery to activate or suppress specific signaling pathways within the brain, neural crest, and facial ectoderm of chick embryos. Specifically, I will alter the dorsoventral character of the forebrain and assess molecular, cellular, and morphological consequences. I anticipate that expression patterns of Bmps will be altered by this treatment, which will lead to facial dysmorphologies. The next two aims will elucidate the role that Bmp signaling plays during facial development. I will dissect the role of Bmp signaling within the neural crest mesenchyme and facial ectoderm by inhibiting the ability of these cells to propagate Bmp signals within the cell. Collectively, the results will allow me to determine how regionalized gene expression patterns in neural crest and ectoderm of the face are controlled by the forebrain, and will also shed light on how Bmp signals control outgrowth of the frontonasal process.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE015901-01A1
Application #
6867466
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Small, Rochelle K
Project Start
2005-01-01
Project End
2006-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
1
Fiscal Year
2005
Total Cost
$75,750
Indirect Cost
Name
University of California San Francisco
Department
Orthopedics
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Hu, Diane; Marcucio, Ralph S (2009) Unique organization of the frontonasal ectodermal zone in birds and mammals. Dev Biol 325:200-10
Hu, Diane; Colnot, Celine; Marcucio, Ralph S (2008) Effect of bone morphogenetic protein signaling on development of the jaw skeleton. Dev Dyn 237:3727-37
Foppiano, Silvia; Hu, Diane; Marcucio, Ralph S (2007) Signaling by bone morphogenetic proteins directs formation of an ectodermal signaling center that regulates craniofacial development. Dev Biol 312:103-14
Marcucio, Ralph S; Cordero, Dwight R; Hu, Diane et al. (2005) Molecular interactions coordinating the development of the forebrain and face. Dev Biol 284:48-61