Cranial neural crest cells are a multipotent migratory cell population which generate the majority of the bone, cartilage, connective tissue and peripheral nervous system of the head and face. Craniofacial abnormalities (ex, first arch syndrome, cleft palate, craniosynostoses) account for approximately one-third of all congenital anomalies and therefore are largely attributable to defects in the formation, migration, proliferation and differentiation of neural crest cells. In order to comprehend the origins of craniofacial abnormalities and develop treatments or methods of intervention, which are critical human health issues, it is vital to understand the genetic and cellular mechanisms that regulate cranial neural crest cell and head development. Sophisticated genetic and cellular analyses have determined that neural crest cell patterning is governed by a balance of signals acquired in the neural tube during their formation together with signals received from the tissues they contact during their migration and differentiation. The cranial mesoderm is one such tissue that interacts extensively with the migrating neural crest cells and recently has been demonstrated to be a key player in patterning both the identity and migration characteristics of neural crest cells in mice. This argues that craniofacial abnormalities, which are attributed to defects in neural crest cell development, may often be the secondary consequence of primary defects in tissues such as the cranial mesoderm. Therefore, the primary goal of this proposal is to characterize the intrinsic and extrinsic cues that regulate cranial mesoderm patterning which will provide unique insights into neural crest cell development, craniofacial morphogenesis, and the origins of craniofacial abnormalities. We are taking a complimentary approach combining mesoderm specific gene discovery via gene chip arrays in mice with mesoderm ablations and transplantations together with analyses in mouse models of craniofacial malformation to test for tissue and gene specific function of the cranial mesoderm during neural crest cell, branchial arch, and craniofacial development. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016082-02
Application #
6899750
Study Section
Development - 1 Study Section (DEV)
Program Officer
Small, Rochelle K
Project Start
2004-07-01
Project End
2009-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
2
Fiscal Year
2005
Total Cost
$397,500
Indirect Cost
Name
Stowers Institute for Medical Research
Department
Type
DUNS #
614653652
City
Kansas City
State
MO
Country
United States
Zip Code
64110
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