16 October

A novel mechanism in neuroblast polarization

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During the development of the nematode worm Caenorhabditis elegans, two sets of neurons are formed on the left and right side of the animal. Even though these neurons have similar functions, they migrate in opposite directions, with cells on the left side of the animal moving towards the posterior and cells on the right side towards the anterior. Researchers from the Korswagen group have investigated this process and discovered that it is regulated via a novel mechanism. The results of their research were published in the scientific journal Development.

The shared first authors of the paper, Annabel Ebbing and Tije Middelkoop, investigated the function of a set of conserved transmembrane proteins that had previously been implicated in the polarization of the Q neuroblasts, the founder cells of the migrating neurons. This polarization is important, because it specifies the direction in which the Q neuroblasts and their descendants migrate along the anteroposterior axis. The researchers used different genetic approaches that involve the molecular scissor CRISPR/Cas9, such as adding tags to the proteins to visualize their location and depletion of the proteins to study their function.

Left (QL) and right (QR) Q neuroblasts that are moving posterior and anterior respectively | Linker (QL) en rechter (QR) Q neuroblasten die respectievelijk naar achteren (posterior) en voren (anterior) migreren.

Signaling of UNC-40, a receptor on the membrane of the Q neuroblasts, is usually controlled by binding of its ligand netrin, and this plays an important role in guiding migrating cells and axons along the dorsoventral body axis. However, the researchers discovered that the migration of the Q neuroblasts along the anteroposterior body axis is controlled by a novel mechanism. In this mechanism, the localization of UNC-40 is not controlled by its ligand, but by the above-mentioned transmembrane proteins, which focus the activity of UNC-40 at the front or back of the Q cells to direct migration along the anteroposterior body axis. Given the evolutionary conservation of these transmembrane proteins, it will be interesting to see whether such a mechanism is also important in mammalian nervous system development.


In addition to her part in the research of this project, Annabel Ebbing also created the cover of the issue of Development in which the paper was published. When asked about the cover in an interview with developmental biologist platform the Node, Ebbing explained: “I started the piece by trying to make an abstract overview of a worm, including a migrating Q neuroblast, using simple lines and dots. Later on, I imported the file in illustrator and made the background. Most covers of Development (if not all) have a dark/black background, so I decided to use dark colors, which made a nice contrast with the black and white worm.”



It is not the first time Ebbing has designed the cover of a scientific journal. Last year for their publication in Developmental Cell she also designed the cover. About her passion for both science and art Ebbing said “I especially love thinking about scientific projects in a more abstract way. For me the process of visualization helps in my understanding of a certain subject.”

Partially overlapping guidance pathways focus the activity of UNC-40/DCC along the anteroposterior axis of polarizing neuroblasts. Annabel Ebbing, Teije C. Middelkoop, Marco C. Betist, Eduard Bodewes, Hendrik C. Korswagen. Development 2019



Rik Korswagen is group leader at the Hubrecht Institute and professor of Molecular Developmental Genetics at Utrecht University.