Grant: Operating Grant

The development of the vertebrate body, including the neural tube and the spinal column, begins during early development and involves complex interactions between a number of different cell populations. Defects in any one of the many events essential to the successful completion of these processes can lead to devastating congenital malformations common in the human population, such as neural tube defects. A number of signaling molecules have been implicated in normal development, including the vitamin A derivative retinoic acid. Such molecules ultimately function by regulating the expression of target genes which then dictate cell behaviour. Work from our group has led to a hypothesis that such signaling pathways function in development in part through complex interactions with the Cdx family of transcription factors (Cdx1, Cdx2 and Cdx4). Indeed, the Cdx transcription factors are emerging as essential regulators of a number of fundamental events essential for normal vertebrate development. However, how these Cdx proteins function and the full scope of their roles in the developing embryo is poorly understood. Novel mouse models developed by our group have revealed new roles for the Cdx transcription factors. In the present application, we propose further analysis of these novel roles, with particular emphasis on defining the critical pathways that are regulated by Cdx members. The information forthcoming from these studies should have important bearing on our understanding not only of fundamental processes related to embryonic development, but may also shed light on the basis for certain congenital defects prevalent in the human population as well as several types of cancer in which Cdx mis-function has been implicated.