10 July

Thesis Defense Euclides Fernandes Póvoa: Finding the way

Back to news

Euclides Fernandes Póvoa, from the group of Rik Korswagen, successfully defended his thesis “Finding the way – Transcriptional regulation of migratory neuroblast lineages in C. elegans” on the 10th of July. During his PhD, Fernandes Póvoa studied the genetic mechanisms that help move and orient cells to their correct locations within an organism, as well as the mechanisms that help genetically identical cells differentiate into specific cell types. These processes of cell migration and cell identity determination are essential for the correct formation of both animal and human organisms; and can lead to disease when they are disturbed or functioning improperly.

As many cells in our bodies, the Q lineage cells migrate to their final destination to give rise to neurons. How these processes are genetically regulated can now be better understood using RNA-sequencing. The images above show the two sister Q lineages (QR and QL) in C. elegans.

Q lineages in C. elegans
A roundworm known as Caenorhabditis elegans (C. elegans) is a helpful model in studying cell lineages and the migration of cells, as researchers have been able to precisely identify the location and the origin of every cell that is present in this small organism. Due to its low anatomical complexity, researchers can use it to understand cell migration and differentiation at the level of a single cell. To do this, Fernandes Póvoa looked at two sister cell lineages in C. elegans, known as Q cell lineages. The cells in these lineages are born in one location of the body and must always migrate to a different location in order to fulfill their purpose. In addition, they undergo an identity change (or differentiation), in which they acquire the identity of neuronal cells. These two properties make the Q lineages particularly suitable for investigating migration and differentiation.

Q lineage-specific mRNA profiling
In recent years, RNA-sequencing has created the possibility of studying gene expression at a genome-wide scale. In order to further narrow this down to a cell or cell lineage scale, researchers use a method known as fluorescence-activated cell sorting (FACS). FACS allows scientists to separate a heterogeneous mix of cells into two or more groups based on the fluorescent characteristics of each cell in the mixture. During his research, Fernandes Póvoa has developed a protocol that improves the generation of C. elegans cell suspensions to allow for more efficient FACS of rare types of cells, such as the aforementioned Q lineage cells.

Using this improved protocol, Fernandes Póvoa was able to sequence the RNA of the Q lineage, and therefore show which genes are active (or inactive) in the cells at different stages of their life course. By looking at the cells during these different stages, he could observe the changes in expression that occur as the cells differentiate and travel to their assigned location, and determine which genes are involved in these processes. Importantly, this was the first time that the expression dynamics of an entire post-embryonic C. elegans lineage was characterized.

A graphical abstract of the improved protocol for preparation of C. elegans cell suspensions, that can then be more efficiently sorted using FACS (shown here in the rightmost panel).

Terminating the cell journey
After looking into factors that direct the Q lineage cells during their journey, Fernandes Póvoa looked into factors that help ensure that the migration of the cells stops successfully after they reach their final destination. He discovered a mechanism by which two cell-to-cell signaling pathways – canonical and non-canonical Wnt signaling – can communicate with each other to ensure that cells stop at the correct location.

 

 

 

After obtaining his M.Sc. degree in 2014, Euclides Fernandes Póvoa joined the lab of Rik Korswagen. After successfully completing his PhD research, he has decided to make a change in his professional path and pursue a career in science advocacy and communication: he is helping the International Society of Developmental Biologists improve their communication and establish a social media presence.