Resolving the functions of uncharacterised signalling proteins using zebrafish (360G-Wellcome-201394_Z_16_Z)

Signalling pathways orchestrate almost all aspects of development. The Schier lab has recently used ribosome profiling to identify numerous previously uncharacterised proteins that are expressed during early embryogenesis in zebrafish and might function as signalling molecules. One of the novel signalling proteins, previously annotated as a non-coding RNA, is Toddler (also called Apela or Elabela). Toddler signals via the APJ/Apelin receptor and promotes cell movement during gastrulation. The cellular and molecular roles of Toddler signalling are not known. My first aim as a Sir Henry Wellcome postdoctoral fellow will be to identify proteins that are regulated by Toddler signalling and reveal the cellular mechanisms that mediate the motogenic function of Toddler. My second aim is to employ a similar ribosome profiling approach to discover uncharacterised signalling molecules involved in the development of the nervous system. I will use genome engineering and take advantage of the complementary experience and expertise of the Schier and Wilson labs in behavioural and neuroanatomical studies to identify and analyse these signals. Their cellular and molecular functions will then be investigated. This project has the potential to discover signals with essential roles in neuronal migration, specification of neuronal identity and diversity, circuit formation and function.