The ability to induce therapeutically bone or cartilage formation would allow clinicians to treat a variety of congenital skeletal syndromes or accelerate bone fracture healing. As a model for such applications, craniofacial skeletogenesis involves the specification of cell fates in a tightly regulated spatiotemporal fashion. In this proposal, three sets of experiments will challenge the plasticity behind cell specification during development of the cranial skeleton, using both directed and unbiased approaches to identify and characterize factors that regulate skeletal cell fates in vivo. In both gain and loss of function approaches, embryonic cells that are known to give rise to specific tissue types (e.g., bone) in the zebrafish hyoid skeleton will be injected with compounds that modify expression of the skeletogenic transcription factors Sox9a, SoxQb, Runx2a, and Runx2b. Using transgenic methodologies combined with single cell clonal analyses, expression of these factors will be tightly correlated with ultimate cell fates. Finally, an unbiased genetic screen for zebrafish skeletal mutants will identify novel factors regulating skeletal cell specification. In total, this proposal will clarify at the cellular level the molecular mechanisms regulating skeletogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DE016778-01
Application #
6936802
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Avila, Albert
Project Start
2006-02-01
Project End
2009-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
1
Fiscal Year
2005
Total Cost
$47,216
Indirect Cost
Name
University of Oregon
Department
Other Basic Sciences
Type
Organized Research Units
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403
Hall, Jane; Jheon, Andrew H; Ealba, Erin L et al. (2014) Evolution of a developmental mechanism: Species-specific regulation of the cell cycle and the timing of events during craniofacial osteogenesis. Dev Biol 385:380-95
Huycke, Tyler R; Eames, B Frank; Kimmel, Charles B (2012) Hedgehog-dependent proliferation drives modular growth during morphogenesis of a dermal bone. Development 139:2371-80
Eames, B Frank; Amores, Angel; Yan, Yi-Lin et al. (2012) Evolution of the osteoblast: skeletogenesis in gar and zebrafish. BMC Evol Biol 12:27
Eames, B Frank; Yan, Yi-Lin; Swartz, Mary E et al. (2011) Mutations in fam20b and xylt1 reveal that cartilage matrix controls timing of endochondral ossification by inhibiting chondrocyte maturation. PLoS Genet 7:e1002246
Solem, R Christian; Eames, B Frank; Tokita, Masayoshi et al. (2011) Mesenchymal and mechanical mechanisms of secondary cartilage induction. Dev Biol 356:28-39
Eames, B Frank; Singer, Amy; Smith, Gabriel A et al. (2010) UDP xylose synthase 1 is required for morphogenesis and histogenesis of the craniofacial skeleton. Dev Biol 341:400-15
Eames, B Frank; Schneider, Richard A (2008) The genesis of cartilage size and shape during development and evolution. Development 135:3947-58
Merrill, Amy E; Eames, B Frank; Weston, Scott J et al. (2008) Mesenchyme-dependent BMP signaling directs the timing of mandibular osteogenesis. Development 135:1223-34
Eames, B Frank; Allen, Nancy; Young, Jonathan et al. (2007) Skeletogenesis in the swell shark Cephaloscyllium ventriosum. J Anat 210:542-54