Project ID CM-HD2023_15

ThemeCM-HD

Co Supervisor 1A Centre for Craniofacial Regeneration and Biology (CCRB), FoDOCSWebsite

Co Supervisor 1B Centre for Craniofacial Regeneration and Biology (CCRB), FoDOCSWebsite

The Role of Extracellular Matrix in Palate Development and Clefting

Cleft palate is a relatively common birth defect arising when the palatal shelves growing from the maxilla (upper jaw) fail to meet and fuse. Understanding this developmental process may help early diagnosis and avoid the costs and pain of the repeated surgeries needed for repair. The directional growth of the palatal shelves requires tissue stiffness and is linked with changes in cell spacing. These properties implicate extracellular matrix (ECM) as critical, but the ECMs structure and material properties are poorly understood.

Objectives:
1. Using mouse models,
2. Establish the presence/absence of fibrillar ECM structures in elevating palatal tissue (Year1).
3. Establish cellular dynamics of directional growth and its ECM-dependence in vivo and in live explants (Years1+2)
4. Charactise collagen function in palate tissue stiffness using mouse knockouts (Year 3)

Techniques:
Advanced microscopy (2-photon second harmonic imaging), live imaging, AFM, FEM, microdissection, anatomy, mouse genetics.

One representative publication from each co-supervisor:

• Economou, AD, Brock, LJ, Cobourne, MT & Green JBA (2013) Whole population cell analysis of a landmark-rich mammalian epithelium reveals multiple elongation mechanisms. Development 140:4740-50.

• Brock LJ, Economou AD, Cobourne MT and Green JBA (2016) Mapping cellular processes in the mesenchyme during 1 palatal development in the absence of Tbx1. J. Anat. 228:464–473.