Craniofacial Development & Stem Cell Biology
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The head is the most complicated structure of the body, housing the brain, sense organs and feeding organs and the commonest birth defects affect organs and tissues of the head. Research investigating the mechanisms that control head development underpins a broader understanding of the genetic basis of craniofacial malformations. A multidisciplinary approach using different experimental models and techniques is employed to investigate cell signaling and transcriptional networks regulating development of craniofacial organs such as teeth, palate, sense organs, salivary glands muscle, skeleton and the brain.
Stem cells are found in most adult organs where they act as reservoirs of cells for continued growth or tissue repair following damage. Stem cells from several different craniofacial organs are being studied to understand their in-vivo function and cell biology and also their potential uses for clinical therapies involving the enhancement of natural repair processes and regenerative approaches to generate replacement tissues and organs for transplantation.
The precise integration of the many forces and growth factors acting upon embryonic tissues such as a simple neural tube is required for the development of complex organs such as the brain. We are interested in how intracellular signalling pathways are coordinated and regulated during the morphogenesis of complex organs and structures. Many cell surface receptors use reversible tyrosine phosphorylation as a means of signal transduction. Studies in a number of biological systems have suggested that these signalling pathways are not merely ON:OFF switches but that subtle differences in signal strength and duration often result in profoundly different outcomes. The broad aim of our research is to understand how signalling is regulated to achieve proper tissue morphogenesis, patterning and cell fate specification.
Cerebellar morphogenesis: The cerebellum is the brains control centre for motor coordination and defects in cerebellar development are often associated with ataxia or medulloblastoma, the most common type of childhood cancer. We are interested in how the cerebellum is constructed during embryonic and early postnatal development. Studies on conditional mid-hindbrain-specific Sprouty mutants have shown that these genes play important roles during postnatal cerebellar morphogenesis and we are investigating this process using inducible, conditional gene inactivation approaches in vivo.
Thymus organogenesis, pharyngeal pouch patterning and DiGeorge syndrome: Our recent experiments have indicated that several essential organs such as the thymus, parathyroid, middle ear and cardiac outflow tract that develop wholly or in part from the pharyngeal apparatus exhibit multiple defects in Sprouty mutant mice. These same organs are affected in 22q11 deletion or DiGeorge syndrome and we are investigating the molecular and developmental basis of these defects in mouse embryos.
Brain defects in CHARGE syndrome: We recently produced mouse models for CHARGE syndrome in which the gene mutated in this syndrome, Chd7, has been targetted. Current research efforts in the lab are focused on elucidating the function of this gene during brain development.
Adult stem cells: Several of the genes and signalling patwhays we study have roles in adult tissue stem cells. We use conditional gene targetting approaches to remove gene function in stem cell populations in the adult to understand their function.
Lab website: http://basson.openwetware.org/
