Craniofacial Research

Every human is derived from a single cell created at fertilisation. All the information required to create a highly complex, three-dimensional, free-living individual is contained in this cell. How this process occurs is one of the oldest scientific questions. Many birth defects arise following errors in the program that controls how normal three-dimensional shapes are achieved.

The Craniofacial Research team focuses on determining how the patterns and shapes of the craniofacial and limb skeleton are established in the early embryo. The majority of birth defects affecting the face also involve malformation of the limbs, indicating the patterning mechanisms in the two systems work in similar ways. By comparing the genetic pathways at work during development of the craniofacial and limb skeletons in animals, researchers are gaining unique insights into how each system is controlled.

In addition, research into human genetics is enabling the team to identify the genes responsible for birth defects, providing a much deeper understanding of how skeletal development is controlled.

Group Leaders: 
Dr Tiong Tan
Clinical Specialist
Dr Naomi Baker
Research Officer

Understanding the causes of birth defects
Birth defects involving the face affect approximately one percent of all babies but the genes involved in most of these conditions are unknown. A genetic approach called ENU mutagenesis allows phenotypes of interest to be identified without any prior knowledge of specific genes involved in the development of the organ system of interest. Once useful phenotypes are established, rapid gene mapping approaches have been developed to identify the mutated gene. The Murdoch Children's Craniofacial researchers have identified the mutated genes in three mouse strains which model the human birth defects known as Jeune syndrome, frontonasal dysplasia and Goldenhar syndrome. Each of these mouse models has major developmental defects in multiple organs. Analysis of the origins of these birth defects will directly contribute to our understanding of what causes these birth defects in humans.

In addition, the team has patient samples from individuals with these conditions and uses data from the mouse models to identify the defect causing genes in humans. This project will provide an opportunity for students to learn developmental biology approaches to understanding human birth defects and gain skills in a wide range of molecular biology techniques. Upon completion of this project, students will be in a strong position to initiate their own research into the genetic and developmental basis of human birth defects.

A novel surveillance system that prevents human birth defects
The signalling networks that regulate patterning and coordinated growth during early embryonic development are essential for the formation of normal, healthy children. Genetic lesions that disturb these networks are responsible for structural birth defects that are common and have an enormous impact on affected individuals and their families. The Craniofacial team researchers have identified a unique surveillance system with a broad role in ensuring the fidelity of embryonic development. Disruption of this system, by over expression of a newly-identified MicroRNA (miRNA) cluster, does not result in specific birth defects, but predisposes embryos to a diverse range of structural anomalies.

Disruption of this system could therefore underpin a wide range of sporadic birth defects in humans. This project will analyse the genes of mice and chicks, but more specifically, the role of the miRNA cluster in the animals’ development. The identification of a surveillance mechanism which monitors the fidelity of tissue and organ formation is completely novel and has profound implications for our understanding of embryonic development and the origins of congenital anomalies.