Research objectives and content
The hindbrain is divided into segmental units called rhombomeres which provide compartments for generating regional diversity in the developing CNS. The Hox homeobox genes encode transcription factors that regulate the regional identities of rhombomeres. In Hoxbl mouse mutants rhombomere (r) 4 has an altered identity leading to abnormal migration of facial motor neurons. Associated with these changes is the loss of the signalling molecule Wnt8C in r4. In this proposal I want to determine if Wnt8C is a direct target of Hoxbl. Using reporter genes in transgenic mice I will map the regulatory regions of the Wnt8C gene to identify r4 specific control elements. In vivo and in vitro assays will examine the ability of Hoxbl or other proteins to bind to these sites. Finally to examine whether Wnt8C is involved in the abnormal migration of the cranial motor neurons, I will use explant cultures from Hoxbl mutants to try and rescue the migratory phenotypes with Wnt8C.
Training content (objective, benefit and expected impact)
I am experienced in molecular biology and transcriptional studies in yeast. By selecting Dr Krumlauf's group I will have the opportunity to learn molecular approaches to vertebrate developmental biology with a focus on my major interest in transcriptional regulation at a leading international centre.
Links with industry / industrial relevance (22)