Making the sea anemone sting with a chromatin modifier
The role of proteins affecting development via chromatin changes is poorly known outside bilaterian animals. Knocking out the Lsd1 gene in Nematostella shows its master role in the differentiation of cnidocytes, cells related to neurons that neutralize enemies by shooting a poisonous harpoon.
Animals are multicellular and contain hundreds or thousands of cell types which specialize in different functions.
To do so cells must express distinct sets of genes which confer these functions, e.g. muscle cells express genes important for contraction while red blood cells express genes required to transport oxygen. Although transcription factors, which bind DNA, are considered the master regulators of these cell-type-specific gene expression programs, other types of proteins also play important roles. One such group of proteins are chromatin modifying enzymes which play roles in turning on and off gene expression and in maintaining the expression of the proper sets of genes in different cell types. These proteins often play specific roles in different cell and tissues; however, most of them are also present in single-celled organisms and they are thus much older than animals. When and how these proteins became important in cell-type-specific gene expression is therefore not clear.
In a paper published this week in Nature Communications, researchers from the Sars Centre and the Department of Biological Sciences have addressed this question using one specific chromatin modifier called Lsd1 as a case study.
The work, carried out in the Rentzsch group in collaboration with group leader Pawel Burkhardt, aimed to understand the expression and function of Lsd1 in the starlet sea anemone Nematostella vectensis. Nematostella is a very useful model for addressing such question as it is part of the phylum Cnidaria (which also contain corals and jellyfish), which separated from other animals early in evolution. By comparing the processes underlying the generation of different types of cells in Nematostella to what is known in classical model organisms such as flies and mice, researchers can unravel which processes were present in early animals and which evolved later.
Chromatin modifier Lsd1 with a suprising effect.
In Nematostella Lsd1 is expressed in every cell (as it is in other animals), but its levels are not the same in all cells. Focusing on the nervous system the researchers were able to show that levels of Lsd1 increase as neural cells differentiate into mature neurons indicating a possible role for Lsd1 in this process. This was particularly exciting as Lsd1 has been well studied in the nervous system of mammals and plays important roles there. Following on from this observation they using genome editing tools to remove Nematostella Lsd1 and then used a combination of RNA sequencing and imaging-based analyses to study its function. Surprisingly although some neural cells seemed to be unaffected by loss of Lsd1, a specific type of Nematostella neural cell called a cnidocyte was completely missing. Cnidocytes are specialized neurons, also called stinging cells, which contain an ejectable harpoon used in defense and prey capture. Further studies showed that Lsd1 is not required for making these cells in the first place, but rather for their maturation into functional miniature weapons.
This study represents the first functional analysis of a chromatin modifier in Nematostella and has shown that chromatin modifiers already played roles in cell differentiation early in animal evolution. According to first author James Gahan, “This finding is an important step in understanding how cell type gene expression programs evolved and the roles chromatin modifiers played in this process. Now that we know that this occurred early in evolution, we can ask the much bigger question of how these proteins, which were already present in our single celled ancestors, became such important players in generating the diversity of cells that we find in our bodies”.