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Researchers engineered a mouse with two additional limbs instead of genitals. But why?
Moises Mallo, a development biologist at the Gulbenkian Science Institute in Oerias, Portugal, and his coworkers were studying one of the receptor proteins Tgfbr1, in a signaling pathway involved in various aspects of embryonic development. They deactivated the Tgfbr1 gene in mouse embryos during mid-stage development to investigate its effects on the development of the spinal cord.
The TGFBR1 gene in human
The Tgfbr1 gene provides instructions for making a protein called transforming growth factor-beta (TGF-?) receptor type 1. Transmitted by the TGF-? receptor complex, these signals trigger various responses by the cell, including the growth and division of cells.
TGF-? receptor type 1 helps prevent cells from growing and dividing too rapidly or in an uncontrolled way, can suppress the formation of tumors.
According to MedlinePlus, more than 10 mutations in the Tgfbr1 gene have been found to increase the risk of developing a form of skin cancer condition. This rare condition, known as Ferguson-Smith disease, is defined by the formation of multiple invasive skin tumors that grow uncontrollably for a few weeks. These tumors then suddenly shrink and leave behind noncancerous scars.
No true external genitalia
According to Nature, Mallo’s student Anastasiia Lozovska came to his office to tell him that she had found out that one of the bioengineered embryos had genitals similar to two extra hind limbs. “I didn’t choose the project, the project chose me,” Mallo remarked.
In many four-legged animals, external genitalia and hind limbs develop from the same early structures.
The research team discovered that Tgfbr1 directs these structures to become either genitalia or limbs. In other words, the deactivation of the protein changed the activity of other genes. That resulted in extra limbs and no true external genitalia.
“We show that despite long evolutionary distance from the ancestral condition, the early primordium of the mouse external genitalia preserved the capacity to take hindlimb fates,” they wrote in the study.
Mice used to obtain embryos were between 3 and 6 months old. The study revealed these embryos were obtained by cesarean section and processed for further analyses.
But why was a specific analysis of the sex of the embryo not included? According to the team, the external genitalia of males and females have no sex differences.
The team now intends to research if Tgfbr1 and its relatives affect DNA structure in other systems, such as metastatic cancer. They are also curious to find out if the same process is behind how reptiles develop their double penis (hemipenis).
“Our work uncovers a remarkable tissue plasticity with potential implications in the evolution of the hindlimb/genital area of tetrapods and identifies an additional mechanism for Tgfbr1 activity that might also contribute to the control of other physiological or pathological processes,” the scientists note in the study.
