Embryology Unit Children's Medical Research Institute

Lab head: Professor Patrick Tam
Location: Children's Medical Research Institute

This project explores the cellular and molecular mechanism of the establishment of the body plan and the formation of organs during embryonic development and elucidates how faults in the morphogenetic process disrupts development using genetic models of birth defects and embryo-derived stem cells.

Lab members: Dr Nicolas Fossat

Gene function and RNA processing in gut endoderm development

Primary supervisor: Nicolas Fossat

This project addresses a fundamental issue of embryonic development at the start of life: the molecular activity controlling the formation of major body parts of the embryo. The epithelium of the primitive gut is formed from definitive endoderm and the muscle and connective tissues are mesoderm-derived. The foregut forms the liver, pancreas, the epithelium of the digestive tract and lungs, the thymus, thyroid and parathyroid glands. The molecular basis for the formation, organization and differentiation of these organs is not well understood, and this project is aimed at contributing to our knowledge of this process. As a first step towards this, we compared the genes expressed in the foregut endoderm of mouse embryos with tissues that do not contain endoderm using microarrays. From this analysis we identified a set of genes that are predominantly expressed in the endoderm and which do not, as yet, have any known function in early development. We are now using a variety of approaches to study the functions of some of these genes during development of the endoderm and its derivative organs. In this project, the effects of reduced or loss of gene function (by knockdown, gene-targeting or gene-trap) and gain of gene function (by electroporation, transfection and transgenesis) will be tested in mouse embryos, embryonic stem cells and other appropriate cell models such as mini-gut organoids.

In particular, we are investigating the function of the RNA binding protein RBM47. We demonstrated that RBM47 is involved in Cytidine to Uridine RNA editing, an unusual post-transcriptional modification, the splicing of transcripts and inlfuencing the stability of RNA. Transgenic mice that lack or overexpress Rbm47 display developmental defects. Current projects aim to identify the ensemble of targets and partners of RBM47 and understand its role in RNA processing for the formation and the physiology of endoderm-derived organs.

Discipline: Applied Medical Sciences, Westmead
Co-supervisors: Patrick Tam
Keywords: Genetics, Molecular biology, Mouse