Mammalian Developmental Genetics
We are interested in the molecular basis of mammalian embryonic development. The craniofacial region, thymus gland and cardiac outflow tract derive from the pharyngeal apparatus, which lies lateral to the developing head. We have demonstrated that the transcription factor Tbx1 is required for the development of the pharyngeal apparatus. Inactivation of one copy of this gene is responsible for the etiology of chromosome 22q11 deletion disorder (22q11DS) in humans.
Mice containing one inactive copy of Tbx1 have mild defects, similar to 22q11DS, while mice with two inactivated alleles of Tbx1 die at birth and have no ears, cleft palate, absent thymus gland and heart defects. We will continue using the mouse as a model to identify genes in the genetic pathway of Tbx1.
Over the last 10 years we have collected over 1,000, 22q11DS patients and their parents. The severity of the syndrome varies greatly. A new program in our lab is to determine whether sequence variants in some of the genes we identify could modify the phenotype in human patients.