An unexpected role for Nanos in cnidarian neural stem cell fate determination

The mechanisms of lineage commitment and acquiring specific cell fate remain obscure and require investigating the role of particular genes involved in these complex processes. To address this issue, I studied the role of Nanos in the nervous system of a cnidarian Hydractinia echinata. Nanos is an mRNA-binding translational repressor, which functions in germ stem cell specification in many species and in posterior patterning in Drosophila. Interestingly, Nanos was also found to be expressed in the nervous system of many animals, although this role is poorly understood. In Drosophila Nanos is important for proper dendrite morphogenesis and for maintaining sodium current and excitability of motoneurons. While Hydractinia Nanos1 mRNA was detected only in germ cells, Nanos2 was also expressed in cells committed to neural fate, from early progenitors to maturing nematocytes. To gain further insight into the biological functions of Hydractinia Nanos2, I studied this gene by ectopic expression in transgenic animals, and by dsRNA and morpholino-mediated downregulation. Nanos2 ectopic expression caused severe defects in animal development. This was manifested by formation of supernumerary and ectopic tentacles (i.e. oral structures), which led to complete oralization in severe phenotypes. Further analysis showed that the reason for the abnormal development is a change in the commitment of early embryonic cells, driving them to make more stinging cells (cnidarian specific sensory cells), at the expense of RFamide+ neurons. The excess of stinging cells possibly induced formation of extra tentacles post metamorphosis. Nanos2 knockdown resulted in reduced proliferation and decrease in the number of stinging cells. Animals also had fewer tentacles following metamorphosis, conversely to Nanos2 ectopic expression phenotype. Nanos' roles in germ cells development and proliferation seem to be ubiquitous in metazoans, but a role for Nanos in specification of neural fates has not been found so far in any other animal. My data also demonstrate that the use of basal invertebrate models can have implications for basic developmental biology and biomedicine.

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University of Galway Theses (PhD Theses)