Our research focuses on explaining a variety of human craniofacial birth defects and providing novel insights into how to better stimulate bone repair in patients.
Facial Skeletal Patterning
Amjad Askary, Bartosz Balczerski, Lindsey Barske
The pharyngeal arches are transient embryonic structures highly conserved in all vertebrates. From the neural crest progenitor cells residing in these arches arise a myriad of highly stereotyped, distinctly shaped cartilages and bones that support the jaw and face. We are interested in how distinct programs of gene expression are established within these skeletogenic neural crest cells, as well as how the cellular behaviors are controlled by these genes that assemble skeletal cells into unique shapes. We use targeted mutagenesis and transgenic tools to remove or misexpress specific genes, combined with high-resolution in vivo imaging to directly follow how cells behave differently when gene function is altered. Our studies are revealing how the precise control of cell fate, movement and multiplication builds distinct skeletal shapes, and how defects in these processes result in the facial dysmorphologies seen in a variety of human birth defects.
Chong Pyo Choe
The epithelial tissues of the face form complex folds that organize development of the head skeleton as well as contribute to a variety of structures such as the mouth opening, pharynx, salivary glands, Eustachian tube and thymus. The pharyngeal epithelial pouches of zebrafish are an excellent system to understand general principles by which epithelial tissues undergo branching and folding during development. Using single-cell-resolution in vivo time-lapse microscopy, we are investigating how multiple signaling pathways are integrated to tightly control the cell behaviors that initiate folds and then organize epithelial cells into stable structures. By studying how the facial epithelia form during development, we hope to better understand why facial epithelial development goes awry in birth defects such as DiGeorge Syndrome.
Ectomesenchyme Potential of Neural Crest
Samuel Cox, Camilla Teng
The evolution and development of the vertebrate head skeleton relies on a completely new cell type derived from the ectoderm adjacent to the neural tube. These “neural crest” cells generate not only neural and glial cell types commonly associated with the neuroectoderm, but also ectomesenchymal cell types such as cartilage and bone-forming cells commonly associated with the mesoderm. We are interested in how this ectoderm-derived population acquires the potential to generate mesoderm-like derivatives as well as how neuroglial and ectomesenchymal fates are later selected. As we have found a remarkably specific role of the replacement histone H3.3 in generating multipotent neural crest cells, we are actively investigating how large-scale chromatin turnover may allow neural crest cells to generate such a wide variety of derivatives.
Dion Giovannone, Sandeep Paul, Simone Schindler
While our bones have some capacity to repair following fracture, the repair of large bone lesions remains an ongoing challenge. As with lizards and many amphibians, zebrafish have remarkable powers of organ repair. In our lab, we find that zebrafish can also repair more than half of their lower jawbone following injury. By developing sophisticated transgenic tools to follow and manipulate cells during adult bone regeneration, we seek to identify the progenitor populations that mediate this repair and the signaling pathways that stimulate these progenitors to multiply and generate new bone. As the development of cartilage and bone is highly conserved between fish and mammals, it is likely that similar progenitors exist in humans. If so, the lessons learned from our fish bone regeneration studies could lead to novel cell-based therapies aimed at improving bone repair in patients.