Hox gene

The blueprints of organisms are deeply anchored genetically: the so-called Hox genes ensure that they form during embryonic development. HOX and TALE genes encode homeodomain (HD)-containing transcription factors that interact in different tissues to coordinate cell fate and morphogenesis during embryonic development (Jia Y et al. 2018).

In the course of embryonic development, various axes must be created in the developing embryo, for example the primary body axis from the head to the tail or close to the body to far from the body in the extremities. The family of Hox genes, a highly conserved subgroup of the homeobox superfamily, a family of transcription factors, plays an important role in this process. This gene family, which in turn regulates other factors, is characterized by the presence of the eponymous homeobox, a conserved sequence that encodes a specific DNA-binding motif and thus enables the regulation of other genes.

Hox genes are organized in clusters and are thought to have evolved from a common ancestor through duplication events. The fruit fly has one cluster consisting of the Antennapedia and Bithorax complex. Vertebrates, on the other hand, have four clusters - HoxA, HoxB, HoxC and HoxD - comprising a total of 39 genes. During embryonic development, Hox genes follow the principle of spatial and temporal colinearity. This means that Hox genes, which are precisely controlled, are switched on one after the other in a precisely defined manner. Not only the time, but also the position on the body axis at which the respective gene is activated is precisely defined.

Hox genes play a crucial role in development and regulate numerous processes such as apoptosis, receptor signaling, differentiation, motility and angiogenesis. Abnormalities in Hox gene expression have been found in abnormal development and malignancy, suggesting that altered expression of Hox genes may be important for both oncogenesis and tumor suppression, depending on the context. Therefore, the expression of Hox genes could be important for diagnosis and therapy (Shah N et al. 2010).

Mutations in the Hox genes lead to malformations such as synpolydactyly (SPD), a hereditary skeletal malformation of the distal extremities. The malformation of the hands and feet is caused by a dominant mutation in the Hoxd13 gene. The disease is inherited dominantly, meaning that one copy of the mutated gene (from the mother or father) is sufficient to develop the clinical picture. If both copies of the Hoxd13 gene are altered (homozygous), the mutation has an even more serious effect.

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