Genetic researchers who study the development of mice have created accidentally mice with unusually long and unusually short tails.
Their findings, published in two articles in the Developmental Cell magazine, offer new insights into some of the key aspects that control the development of tails in mice and have implications for understanding what happens when pathways of development fail.
"The same regulatory networks that control the mechanisms that regulate how a body pattern is formed are often co-opted for other development processes," says Moisés Mallo, a researcher at the Gulbenkian Institute of Ciência in Lisbon, Portugal, and lead author of one of the two articles "The study of these networks can provide relevant information to understand other development processes, or even pathological."
The findings of both groups are related to a gene called Lin28, which was already known to have a role in the regulation of body size and metabolism, among other functions.
"We were trying to make models of mice with the gene that predisposes to cancer Lin28, but we were surprised to find that these mice had super-long tails, they had more vertebrae," says George Daley, researcher and dean of Harvard Medical School and lead author of the other article. His team was studying the Lin28 / let-7 route, which regulates development time and has been implicated in several types of cancer.
Mallo, on the other hand, was studying a gene called Gdf11, which was already known to be involved in triggering the development of the tail during embryonic development. In their laboratory, they found that mice with Gfd11 mutations had shorter and thicker tails than those of normal mice. "They also contained a neural tube fully developed inside, as opposed to a normal tail that is essentially made of vertebrae," says Mallo. "We were able to identify the Lin28 and Hox13 genes as key regulators of tail development in the last stage of Gdf11."
Both pathways are related to the development of somites, which give rise to important structures associated with the body plan of vertebrates. These cell blocks eventually differentiate into dermis, skeletal muscle, cartilage, tendons and vertebrae. As mammals develop, the somites are sequentially established along the axis of the body. Lin28 plays a role in regulating the time of this repetitive process.
"From my perspective, one of the most important findings of our work is that a group of multipotent cells that build both the somites and the spinal cord are regulated by fundamentally different genetic networks and have different cellular competencies in two consecutive stages of development." Says mallo "This finding goes beyond the transition from trunk to tail, possibly acquiring relevance in pathological processes such as the onset of metastasis."
"There are also important implications in this research for understanding evolution," says Daisy Robinton, a Harvard researcher and first author of Daley's lab study. "The lengthening of the anterior-posterior axis is an important feature in bilateral animals, and natural selection has created a variety of tail lengths to adapt to different evolutionary pressures." Until now, little was known about how length is controlled and how the manipulation of genetics can affect morphogenesis. "
Robinton says the next steps for Daley's lab are to address the question of whether Lin28 / let-7 acts similarly in other organ systems, as well as to explore more deeply how this pathway influences decisions about the fate of cells during the development of mammals.
For Mallo, future work will focus on discovering more molecular details of how these players modulate the activity of tail-budger progenitors and deepen understanding of how these molecular interactions are mediated.