Functional attributes of TWIST1 interactome on ectomesenchymal differentiation in craniofacial development
The basic-helix-loop-helix (bHLH) factor plays pleiotropic roles in craniofacial development. TWIST1 complexes with E-proteins via the helix domain, and with chromatin modifiers via the N-terminal domain. The array of TWIST1 heterodimers and the TWIST1 complexes underpin the diversity of molecular function required for cell type specification during embryogenesis. Functional analyses of the loss and gain of TWIST1:E-protein dimer activity revealed previously unappreciated roles in guiding lineage differentiation of embryonic stem cells. Dimer formation and the balance of dimer types are altered by disease-causing mutations in TWIST1 helix domains, which may explain the defective differentiation of the craniofacial mesenchyme observed in clinical conditions. Complexes of TWIST1 and chromatin remodelling proteins acts as regulators in the neural crest cells for establishing the enhancer repertoire in poising neural differentiation of the bipotential progenitors and maintaining the ectomesenchymal potential following lineage specification. The transcriptional output of TWIST1-chromatin remodeller at different phases of neural crest lineage development underpins the impact of the loss of Twist1 function in craniofacial malformation.
Prof Tam is the Head of the Embryology Unit and Senior Principal Research Fellow at the Children's Medical Reearch Institute, University of Sydney. His research focuses on the systems-based investigation of the functional attributes of gene regulatory network in body patterning during mouse development and the differentiation of stem cells. The embryological analysis of cell fates, together with the developmental spatial transcriptome analysis of the gastrulating embryo at cell population and single cell resolution, revealed the cellular and molecular mechanisms that underpin cell lineage development and the organization of the basic body plan of the early embryo. The in-depth knowledge of lineage differentiation during early embryogenesis guides the first steps of differentiation of stem cells into clinically useful cell types for cellular therapy. Patrick Tam is the lead investigator of the Centralized Capacity of Functional Genomics of the Luminesce Alliance Paediatric Precision Medicine Program, and conducts research on the genetics and disease modelling of craniofacial developmental defects and neurodevelopmental disorders.
Host: Prof David Tremethick, Genome Sciences Department