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Sensory organ and receptor cell diversification in development and evolution

Supervisor: Clare Baker

Fundamental questions in biology include how different organs and cell types are specified during development, for which the lateral line system of fishes and aquatic amphibians provides an excellent model. Ancestrally within jawed vertebrates, the lateral line system comprises lines of mechanosensory 'neuromasts', containing hair cells - like vestibular inner ear hair cells - that respond to local water movement ("touch at a distance"), flanked on the head by electrosensory 'ampullary organs', containing electroreceptors that respond to weak bioelectric fields (primarily used for hunting). A series of lateral line placodes (bilateral patches of thickened ectoderm) on the head elongate to form sensory ridges. A line of neuromasts forms along the centre of each ridge, while ampullary organs differentiate on the flanks. Hence, the lateral line is a superb model for understanding the mechanisms underlying the diversification of different types of sensory organs.

Lateral placode and neuromast development are intensively studied in zebrafish, but this teleost fish lacks the electrosensory system. To identify candidate genes likely to be important for electroreceptor development, we took an unbiased approach, using comparative RNA-Seq in the paddlefish (a non-teleost electroreceptive fish) to generate a lateral line organ-enriched gene-set. Validation of a variety of candidate genes revealed close developmental and evolutionary links between electroreceptors and hair cells (Modrell et al., 2017, eLife).

The PhD objectives are to identify molecular mechanisms important for neuromast/hair cell versus ampullary organ/electroreceptor development, and test whether they are conserved or lineage-specific. This will be achieved by cloning and validating the expression of candidate genes from the paddlefish data-set during lateral line development in a related, experimentally amenable non-teleost fish (sturgeon); comparing the expression of validated candidates in zebrafish; and investigating the function of the most promising candidates using small-molecule agonists/antagonists (where available) and/or CRISPR/Cas9.

 

Relevant references

Modrell MS, Bemis WE, Northcutt RG, Davis MC, Baker CVH (2011) Electrosensory ampullary organs are derived from lateral line placodes in bony fishes. Nature Communications 2, 496. (PMID: 21988912)

Piotrowski T, Baker CVH (2014) The development of lateral line placodes: Taking a broader view. Developmental Biology 389: 68–81. (PMID: 24582732)

Modrell, M.S., Lyne, M., Carr, A.R., Zakon, H.H., Buckley, D., Campbell, A.S., Davis, M.C., Micklem, G., Baker, C.V.H., 2017. Insights into electrosensory organ development, physiology and evolution from a lateral line-enriched transcriptome. eLife 6: e24197. (PMID: 28346141)