The latest addition to the six-legged creature category isn't an insect but a rodent – with its native genitalia relocated to its hind legs. On March 20th, a study published in Nature Communications unveiled research into genetically engineered rodents, shedding light on how alterations in DNA's three-dimensional structure can influence embryonic development.
Image Source: Anastasiia Lozovska et al.
Moisés Mallo, a developmental biologist at the Gulbenkian Institute of Science in Portugal, and colleagues are delving into a receptor protein called Tgfbr1 in a signaling pathway that involves many aspects of embryonic development. Scientists deactivated the Tgfbr1 gene in mouse embryos halfway through development to understand how this alteration affects spinal cord development.
Subsequently, Anastasiia Lozovska, a graduate student under Mallo, noticed that one of the genetically engineered embryos had reproductive organs that resembled two extra hind limbs. Her discovery took the research down an unexpected path. "It wasn't me choosing the project; it was the project choosing me," Mallo said.
In most quadruped animals, the development of hind limbs and external genitalia (penis or clitoris) originates from the same primordium. To investigate the specific regulatory mechanisms of Tgfbr1, researchers selectively deactivated the Tgfbr1 gene in the tail bud region of mouse embryos, resulting in an unexpected phenotype: tissues that typically give rise to external genitalia developed into a second set of hind limbs, resulting in a mouse embryo with six legs.
Further investigation revealed that Tgfbr1 regulates the development of specific structures into external genitalia or limbs by altering the folding of DNA in cells. Complete inactivation of Tgfbr1 led to changes in the activity of other genes, resulting in mice lacking external genitalia but with extra limbs.
In future studies, researchers hope to further determine whether Tgfbr1 and related genes affect DNA structure in other tissues such as metastatic cancers or the immune system, and will also investigate whether the development of reptilian external genitalia is regulated by the same mechanism.
Related paper information: https://doi.org/10.1038/s41467-024-46870-z
