Among their many extraordinary feats, some flatworms from the planarian family reproduce by breaking off pieces of themselves to regenerate new worms. Now, researchers at the Stowers Institute for Medical Research have discovered that this process is controlled by Hox genes which are a family of genes that are known to control important aspects of early development.
The research, published online on November 18, 2021, in Nature Communications, suggests a new function of these genes in adulthood. Hox genes continue to be expressed in adult tissues and are misregulated in some human cancers. However, their functions in these adult contexts are not fully recognized, according to lead author Christopher Arnold, PhD.
“By finding new functions for Hox genes we can begin to fill in the gap in our understanding of the functions these genes play in adult animals, both naturally and in disease,” said Arnold, an assistant professor in the lab of Alejandro Sanchez Alvarado, PhD, Stowers executive director and chief scientific officer and Howard Hughes Medical Institute investigator.
Hox genes are considered to be some of the most important genes of developmental biology. In multiple organisms, these genes have been shown to map out the body plan of the developing embryo along its anterior-to-posterior axis, or from head to tail. Arnold said that Arnold was puzzled by the absence of Hox genes in flatworms in his system.
The Sanchez Alvarado Lab studies asexual planarians ( Schmidtea mediumea). They have no embryonic stage; they are adults who are in an eternal state. In the past, they did not appear to have the anatomical segments that Hox genes normally create to help organise an organism’s body plan from end to the end. Arnold and his colleagues discovered in 2019 that planaria are actually segmented. When they squished the bodies of the tiny organisms with an encasement the flatworms broke apart into multiple, regularly spaced segments.
Because one of those segments exactly matched the part flatworms that reproduce break off when they reproduce The researchers speculated that Hox genes were involved in reproduction asexually. They also observed how each of the Hox genes affected the organism’s capability to reproduce in a dish.
Typically, when a flatworm reproduces asexually it begins by anchoring its tail to a solid surface, such as an underwater rock or petri dish. Then, it crawls in the opposite direction, undulating its midsection and stretching its body until finally it reaches a point at which, like a rubber band breaks, leaving a tiny piece behind.
Researchers found that five of the 13 Hox genes were necessary for the worms’ ability to complete their task. They also found that two of these five genes had opposite impacts on the segmentation process and behaviors that are associated with sexual reproduction. Eliminating the Hox3 gene resulted in worms with longer segments from head to tail that were constantly trying to reproduce, whereas knocking down the post2b gene completely eliminated the behavior and segments altogether.
Arnold stated, “We found that Hox genes were not just present in adult animals but were also essential for an exclusively adult animal activity like sexual reproduction.” The findings of the researchers suggest that a lot of the genes believed to be only relevant in embryonic development might play a role later on in adult health and diseases.
It could be that our understanding of what these genes do is not sufficient. We may not know all the details, therefore we must be open to new ideas.
Alejandro Sanchez Alvarado, Senior Author
The team is planning to continue to study asexual reproduction in order to gain new insights into the development processes that underlie the behavior of adult animals, their regeneration, and growth.
Arnold, C.P., and. (2021) Hox genes regulate sexual reproduction and tissue segmentation in adult animals. Nature Communications. doi.org/10.1038/s41467-021-26986-2.
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