Mechanisms of cardiopharyngeal differentiation

The pharyngeal apparatus (PhAp) is an embryonic structure from which many organs develop, such as most of the heart, thymus, parathyroid glands, muscles, and other craniofacial tissues. Developmental anomalies of the PhAp are at the basis of some of the most frequent congenital anomalies, such as congenital heart disease, some immunodeficiencies, craniofacial anomalies. We recently found that the Tbx1 gene, mutations of which can cause DiGeorge syndrome, regulates the distribution (regionalization) of cells within the PhAp during embryonic development. We hypothesize that alteration of regionalization is at the basis of at least some of the developmental anomalies associated with DiGeorge syndrome. In this project we propose to investigate the developmental mechanisms responsible for regionalization and propose the use of drugs to reduce their incidence in a mouse model of the genetic disease.
            We expect that by the end of this project we will have defined the developmental mechanisms by which TBX1 regulates regionalization, and we will lay the basis for further molecular genetics studies to dissect a genetic network governing interactions among lineages contributing to the PhAp.