High resolution gene expression maps of Caenorhabditis elegans

Researchers of the Korswagen group and the Van Oudenaarden group have generated a valuable resource to study genome wide spatial gene expression patterns in the nematode C. elegans. Using this resource, they have identified novel genes involved in male fertility. The researchers have published their findings in Developmental Cell.

The development of the small nematode, or roundworm, C. elegans has been very well characterized and the origin of each cell is precisely known, making it a powerful model to study development, nervous system function and physiology. During the past decades, genetic studies have identified many of the genes that are involved in these processes. However, to obtain more detailed insight into the gene expression programs that underlie the specialization of different cells and tissues, a comprehensive overview of gene expression patterns is needed.

The Korswagen and Van Oudenaarden groups have jointly developed a high resolution in silico resource of gene expression along the antero-posterior axis in C. elegans. By using and further refining a technique that was developed at the Hubrecht Institute, called tomo-seq, the researchers were able to map the expression of the majority of genes along the antero-posterior body axis of C. elegans. To do this, young adult animals were sectioned head to tail into very thin slices, from which the RNA was extracted for sequencing. Next, sequence information from the individual slices was put back into the right order to generate antero-posterior gene expression maps.

To explore the expression maps, the researchers developed computational methods to discover region and tissue-specific genes. They used these tools to describe gene expression programs of the major tissues and organs, but focused on one key question: what are the differences between male and hermaphrodite sperm, and what is the role of the male reproductive tract in male fertility.

A population of C. elegans is mostly hermaphroditic, which means that the animals have generated sperm cells that are used to fertilize their own oocytes. However, there are also males and when these mate with hermaphrodites, their sperm outcompete the sperm cells of the hermaphrodite. Why male sperm is dominant over hermaphrodite sperm is still largely unknown, but may be linked to the larger size and increased migration speed of male sperm cells. By generating and comparing gene expression maps of hermaphrodites and males, the researchers were able to identify male specific sperm genes that likely play an important role in this process. Moreover, they also identified genes that are specifically expressed in the male reproductive tract. Interestingly, these include secreted proteins that are required for male fertility, indicating that these are novel seminal fluid components that are required for normal sperm physiology.

What makes spatial transcriptomics especially powerful in C. elegans is the invariant anatomy of the animal. Because cells are always at the same position, expression maps from different animals can be precisely aligned and compared. This will open up new possibilities for studying the effect of mutations or other perturbations on the global gene expression landscape.

Spatial transcriptomics of C. elegans males and hermaphrodites identifies sex-specific difference in gene expression patterns. Annabel Ebbing, Ábel Vértesy, Marco C. Betist, Bastiaan Spanjaard, Jan Philipp Junker, Eugene Berezikov, Alexander van Oudenaarden and Hendrik C. Korswagen. Developmental Cell 2018.

Gene expression resource: http://celegans.tomoseq.genomes.nl/

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

Alexander van Oudenaarden is director of the Hubrecht Institute, group leader and professor of Quantitative Biology of Gene Regulation at the University Medical Center Utrecht and Utrecht University.