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The evolution of the neurogenic gene regulatory networks in bilateria

Primary Supervisor: Dr Roberto Feuda

Secondary supervisor: Dr Ezio Rosato

PhD project title: The evolution of the neurogenic gene regulatory networks in bilateria

University of Registration: University of Leicester

Project outline:

The evolution of the nervous system is one of the most important innovations in the evolutionary history of animals. Because neurons are present in deuterostome (e.g. human and sea urchin) and protostome (e.g. flies), we can infer that the common ancestor of these animals (i.e. the common bilateria ancestor) had neurons. From a developmental perspective, neurons in bilateria arise from cells that are part of the ectoderm1. The process of neuronal specification can be dissected in a few steps, and it relies on orthologous transcription factors1. However, despite these similarities, whether neurons in different bilateria are patterned using a conserved or divergent regulatory program remains an open question. This uncertainty can be summarized in two main competing hypotheses. The first predicts that the similarities in gene expression are the result of a highly conserved gene regulatory network (GRN) which specify the neurons in bilateria [e.g. kernel sensu2]. The second predicts neuronal specification in bilateria relies on orthologous genes that are wired differently in the GRN3.

The aim of this proposal is to test these two hypotheses by identifying and comparing the neurogenic GRNs in two distant related bilateria species and finally to test at the molecular level the conservation of the GRNs architecture. The two species that will be used are the purple sea urchin Strongylocentrotus purpuratus (a deuterostome which is a distantly related cousin of humans) and the fruit fly Drosophila melanogaster (a traditional model system used to model human diseases). These have been chosen because they are well-established models for studying development (e.g. they have well-established protocols), and because their phylogenetic position is important to determine the evolution of the neurogenic GRN in animals with bilateral symmetry.

The key objective of this research programme is to test whether neurons in bilateria are patterned using conserved or divergent GRNs. This proposal has the following objectives:

  • Identify the apical neurogenic GRN in purple sea urchin larvae.
  • Identify the neurogenic GRN in the Drosophila larval brain.
  • Test the conservation of neurogenic GRN in Bilateria

References:

  1. Hartenstein, V. & Stollewerk, A. The evolution of early neurogenesis. Dev Cell 32, 390–407 (2015).
  2. Davidson, E. H. & Erwin, D. H. Gene regulatory networks and the evolution of animal body plans. Science 311, 796–800 (2006).
  3. Wagner, G. P. Homology, genes, and evolutionary innovation. (Princeton University Press, 2014).

BBSRC Strategic Research Priority: Understanding the Rules of Life: Neuroscience and behaviour

    Techniques that will be undertaken during the project:

    • Extensive data generation and data analysis of large data sets will be required
    • Molecular biology involving gene cloning and protein expression strategies.
    • Generation and maintenance of transgenic fly lines
    • Drosophila genetics and functional perturbation
    • Bioinformatics
    • Genomics

    Contact: Dr Roberto Feuda, University of Leicester