Agenda

The nervous system of bilaterian animals is largely bilaterally symmetric. However, some left-right asymmetries exist at the anatomical, molecular and functional levels. One particularly interesting case is the example of morphologically symmetric structures that display molecular and functional left-right asymmetries. However, the extent of such molecular and functional asymmetries remains poorly characterized. C. elegans is a particularly interesting model organism to address this question, because it allows us to analyze left-right asymmetries in the nervous system with a single-neuron resolution. The main aim of my PhD was to identify novel molecular asymmetries in the nervous system of C. elegans. For this purpose, I used the bilaterally symmetric lineage of AIY neurons. Previously, it was shown that a neural bHLH transcription factor, HLH-16/Olig, is left-right asymmetrically expressed in the AIY neuron lineage, regulating AIY axonal projections in a left-right asymmetric manner. However, the targets of HLH-16 involved in this process were unknown. During my PhD, using a combination of single-cell RNA-seq data analysis and candidate approaches, I identified the ephrin protein EFN-2 and the Flamingo protein FMI-1 as downstream targets of HLH-16 and found that they are left-right asymmetrically expressed in the AIY lineage. I showed that EFN-2 and FMI-1 collaborate in the left-right asymmetric regulation of AIY axonal growth. In this process, EFN-2 may act via a non-canonical receptor of the L1CAM family, SAX-7. My study suggests that even structures that are bilaterally symmetric at the morphological level can display molecular left-right asymmetries and asymmetric developmental genetic programs. Overall, my work reveals novel molecular left-right asymmetries and their functional consequences in the C. elegans nervous system.