Accidental outcomes tell a tale of mouse tails
Two labs made the same unexpected but valuable discovery. Nick Carne reports.
Two different research teams have created mice with unusually long or short tails, even though neither was trying to do either.
They agree, however, that their fortuitous findings could help us better understand the process of development or disease, and what happens when developmental pathways go awry.
Both studies involved a gene called Lin28, which was already known to have a role in regulating body size and metabolism, among other functions. But that’s where the similarities end.
In the US, George Daley and colleagues at Boston’s Harvard Medical School were studying the Lin28/let-7 pathway, which regulates developmental timing and has been implicated in several types of cancer.
"We were trying to make mouse models of Lin28-driven cancer, but we were surprised to find that these mice had super long tails; they had more vertebrae," Daley says.
Across the Atlantic in Portugal, a team from Lisbon’s Instituto Gulbenkian de Ciência was actually studying a gene called Gdf11, which is known to be involved in triggering the development of the tail during embryonic development.
Moisés Mallo and colleagues found that mice with Gfd11 mutations had tails that were shorter and thicker than those of regular mice, and they identified Lin28 as one of the two key regulator genes of tail development downstream from Gdf11.
Both pathways relate to the development of somites, which give rise to important structures associated with the vertebrate body plan. These blocks of cells eventually differentiate into dermis, skeletal muscle, cartilage, tendons and vertebrae.
As mammals develop, the somites are laid down sequentially along the body axis. Lin28 plays a role in regulating the timing 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 cell competences at two consecutive stages of development," Mallo says.
"This finding goes beyond the trunk to tail transition, possibly acquiring relevance in pathological processes like the initiation of metastasis."
Harvard’s Daisy Robinton suggests there are also important implications for understanding evolution.
"Anterior-posterior axis elongation is an important feature in bilateral animals, and natural selection has created a variety of tail lengths to suit different evolutionary pressures,” she says. “Until now, little was known about how length is controlled and how the manipulation of genetics can impact morphogenesis."