We are studying the molecular pathways involved in craniofacial patterning and heart development and their role in the pathology of congenital disease. A large number of congenital malformations affecting infants involve either craniofacial structures or the heart, leading to substantial morbidity and mortality. Interestingly, many congenital syndromes result in abnormalities both in craniofacial development and cardiac development suggesting that the molecular signals involved in the development of these two different organ systems are shared. Yet, the identities and the biological roles of many of these signals are still not well defined. Here, we will develop genetic approaches using both a forward and reverse screen in Xenopus that will be integrated with ongoing cellular and biochemical approaches in our two labs to investigate the genetic control of craniofacial pattern formation and heart development.

Public Health Relevance

Our primary goal is to better understand the basic biology and pathobiology of craniofacial and cardiac development. To this end, we will use the model organism Xenopus tropicalis to conduct forward and reverse genetics screens to generate animal for human disease states and to identify the molecular pathways involved in the development of cardiac and craniofacial tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE018825-04
Application #
8197173
Study Section
Special Emphasis Panel (ZRG1-GGG-T (52))
Program Officer
Scholnick, Steven
Project Start
2008-12-01
Project End
2013-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
4
Fiscal Year
2012
Total Cost
$457,273
Indirect Cost
$74,537
Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Dorr, Kerry M; Amin, Nirav M; Kuchenbrod, Lauren M et al. (2015) Casz1 is required for cardiomyocyte G1-to-S phase progression during mammalian cardiac development. Development 142:2037-47
Charpentier, Marta S; Tandon, Panna; Trincot, Claire E et al. (2015) A distinct mechanism of vascular lumen formation in Xenopus requires EGFL7. PLoS One 10:e0116086
Griffin, John N; Sondalle, Samuel B; Del Viso, Florencia et al. (2015) The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus. PLoS Genet 11:e1005018
Amin, Nirav M; Gibbs, Devin; Conlon, Frank L (2014) Differential regulation of CASZ1 protein expression during cardiac and skeletal muscle development. Dev Dyn 243:948-56
Sojka, Stephen; Amin, Nirav M; Gibbs, Devin et al. (2014) Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity. Development 141:3040-9
Amin, Nirav M; Tandon, Panna; Osborne Nishimura, Erin et al. (2014) RNA-seq in the tetraploid Xenopus laevis enables genome-wide insight in a classic developmental biology model organism. Methods 66:398-409
Amin, Nirav M; Greco, Todd M; Kuchenbrod, Lauren M et al. (2014) Proteomic profiling of cardiac tissue by isolation of nuclei tagged in specific cell types (INTACT). Development 141:962-73
Kaltenbrun, Erin; Greco, Todd M; Slagle, Christopher E et al. (2013) A Gro/TLE-NuRD corepressor complex facilitates Tbx20-dependent transcriptional repression. J Proteome Res 12:5395-409
Tandon, Panna; Miteva, Yana V; Kuchenbrod, Lauren M et al. (2013) Tcf21 regulates the specification and maturation of proepicardial cells. Development 140:2409-21
Jonas, Stephan; Zhou, Elaine; Deniz, Engin et al. (2013) A novel approach to quantifying ciliary physiology: microfluidic mixing driven by a ciliated biological surface. Lab Chip 13:4160-3

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