When the embryo is developing, the body's construction plan will be formulated and implemented within a few days. Known as the "architect", the Hox gene family is responsible for coordinating the development of the limbs and spine, and issuing precise instructions at specific times.
Researchers at the University of Geneva and the Swiss Federal Institute of Technology found that the arrangement of the Hox gene on the chromosome follows the order in which the corresponding structures appear, such as from the shoulder to the arm to the hand. Studies have shown that, based on the above arrangement, different regulatory domains can coordinate the development of limb components at the topological level.
In the process of limb formation in mice, the Hoxd gene cluster is divided into two batches for transcription, first developing into upper and lower limbs, and then forming palms. "
In this study, the researchers discovered another regulatory region, which is located at the other end of the Hoxd gene cluster and is responsible for the development of the upper and lower limbs. They found that some Hoxd genes are only associated with one of the two regulatory domains, and some interact with both.
In order to analyze the molecular process of limb formation and understand the developmental transition from upper limbs, wrists to palms, the researchers used complex genetic engineering and molecular biology techniques to study the mouse embryonic cell lines. "What makes us curious is that some Hoxd genes are involved in both the formation of the upper and lower limbs and the formation of the palm, but these genes are not expressed during wrist development," said Dr. Guillaume Andrey, the first author of the article.
The researchers pointed out that there are two topological domains at each end of the Hoxd gene cluster, and these two domains perform distinct regulatory functions. The regulatory domain near the telomere first initiates transcription related to upper and lower limb development, while the regulatory domain near the centromere then initiates transcription related to palm development. At different stages of development, specific Hoxd genes switch between the above two regulatory domains and interact with the two through conformational changes, respectively. This is equivalent to a genetic transcription switch, which sends signals to achieve the developmental transition from upper limbs to palms.
However, there is still a middle zone between these two regulatory domains, which is separated from the control of the two regulatory domains, which is equivalent to the switch's gap and does not activate gene transcription. It is this area that creates morphological joints between the upper and lower limbs and the palm.
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