OVERVIEW

Formation of the vertebrate facial structures requires coordination of complex molecular and morphogenetic cues. The genes regulating facial development are well conserved across vertebrate species, where minor molecular variations contribute to dramatic alterations in form.

We take advantage of the versatility of forward and reverse genetics in zebrafish as a model to assay function of human cleft candidate genes and demonstrated that the zebrafish palate (ethmoid plate) is morphogenetically homologous to the mammalian primary palate (Dougherty, Development, 2013). We also showed that convergence and extension mechanisms operate in palate morphogenesis, and we are dissecting the Wnt pathway genetically (Rochard, Development, 2016; Kamel, Developmental Biology, 2013).

Advances in clinical treatment of congenital craniofacial malformations require improved understanding of the developmental genetic basis of facial morphogenesis. Our goal is to investigate fundamental genetic regulation of facial development, with focus on translating basic science discoveries to clinical treatments.

CLP Functional Genomics Pipeline

Vertebrate Craniofacial Morphogenesis

We are applying zebrafish to carry out high throughput functional genomics studies, to characterize human genes implicated in orofacial clefts (Mukherjee, Human Molecular Genetics, 2016; Gfrerer, Plastic and Reconstructive Surgery, 2014). We are also using zebrafish as the biological platform to identify chemicals that specifically regulate craniofacial morphogenesis, or even discover compounds that mitigate malformations (Kong, Chemistry & Biology, 2014).

With continued revolutionary advance in human gene sequencing approaches, there is pressing need to bridge the gap between whole genome analysis and clinical use of this data. Determination of pathogenicity of human gene variants is a major challenge in the field, limiting clinical usefulness of WGS information. We apply functional assays in iPSC and zebrafish models toward functional analysis of human gene variants associated with cleft and craniofacial anomalies (E BH Li, Plos Genetics, 2017).