The path to the five -falsehood

When the vertebrates began to be selected on land, their fins turned into paws, and the rays of fins into the fingers. The first notebooks (terrestrial vertebrates with four limbs) had a lot of fingers, but then there were five of them, and since then, five -pound is characteristic of all terrestrial vertebrates.

Until recently, the reason for this phenomenon remained a mystery, which, perhaps, was unraveled by the specialists of the Montreal Institute of Clinical Research, the University of Montreal and the University of McGill (Canada) under the leadership of Dr. Marie Kmita. According to scientists, the five -fad arose as a result of a change in the regulation of the HOXA11 gene in embryonic rudiments of the limbs [1] .

NOKh genes - transcription factors that regulate the embryonic development of animals. These genes are several dozen, they are grouped into four complexes: Noh, NOKhV, Nohs and Nohd. The clusters of Noh and Nohd participate in the formation of fins and paws, including NOKHA11 , NOHA13 and NoHD13 genes.

However, there are two significant differences between fish and tetrapods. In terrestrial verts, the extremities in the kidneys is expressed much more actively than in the rudiments of the fins. In addition, at the tetrav (frogs, mice and birds), the NOX11 genes work in the proximal part of the kidney kidney (closer to the body), and Noh13 in the distal one, where fingers should form [2]. Their expression zones practically do not overlap. Meanwhile, in different fish having paired fins (sharks, jeselonos, Danio), there is no such disunity (Fig. 1).

Rice. 1. The genes of Noha11 and Noh13 are expressed together in the rudiments of the fins; In the buds of the limbs of the tetrae of their area, expression do not overlap (Leite-Castro et al., 2016, with modification)

There are two hypotheses explaining why Noha11 does not work in the distal part of the limb. According to one of them, the activity of the gene is suppressed by NOKHA13 / NohD13 proteins, which are a lot in this area (Fig. 2). According to the second, the expression of NOKHA11 is prevented by the antislayed RNA, which is associated with the sequence of the gene.

Rice. 2. Fields of expression of the genes of NOHA11 and NOHA13 in the kidney of the limb of the mouse (Kherdjemil et al., 2016)

Canadian scientists suggested that it was the mutually exclusive expression of NOHA11 and NOKHA13 in the rudiments of the limbs of Tetra -Plane led to the formation of five -falsehood. They proved this with the help of numerous lines of transgenic mice, and this is the picture as a result.

NOKHA11 consists of two encoding areas (exons), separated by an intron - non -dodging DNA. In the first exon of NOHA11 and the antisectional RNA is synthesized. These molecules are associated with the encoding part of the gene, actually blocking its reading and protein synthesis (Fig. 3). Antimatic RNA RNA11 was found only in the distal part of the kidney, the area of their presence coincides with the area of the "silence" of the gene.

Rice. 3. Regulation of the work of NOHA11. NOKHA13/NohD13 proteins interact with the Enhanser located in Intron, and initiate the transcription of the antislay RNA, which blocks the expression of the gene. The numbers indicate exons

The transcription of antisectional RNA is initiated by NOKHA13 / NohD13 proteins, which are actively synthesized in the distal region of the future limb. They interact with a special area - an enhane, who is located in the intron Noha11. Enhananser, in turn, triggers the synthesis of antislayed RNA.

Thus, Canadian researchers have combined both hypotheses: the NOX13 protein regulates the synthesis of the antislay molecule and the expression of the NOKHA gene11. In mice, mutant according to NOX13 , antislayed RNAs are not formed, and the Noha11 gene works in the zone of fingers. The same picture is observed when the NOX13 genes are in order, and Noha11 is deprived of the Enhanerar. In both cases, polydactylia develops in mutant mice, and up to seven fingers form on the paw (Fig. 4).

Rice. 4. The mice on the paws of five fingers (left), but if the NOHA11 gene is active in the distal part of the future limb, the number of fingers reaches seven (on the right). Kherdjemil et al., 2016, with modification

The fish have neither anti -sample RNA NOHA11 nor ENCHANSERS. This method of regulating the activity of NOCHA11 appeared in the first tetrand, and in modern enhancer sequence is very conservative. The emergence of Enhanser led to the mutually exclusive expression of Noha11 and Noh13 and the formation of five -falsehood.

Natalia Reznik

1. Kherdjemil Y., Lalonde RL, Sheth R., Dumouchel A., De Martino G., Pineault KM, Wellik DM, Stadler HS, Akimenko Ma, Kmita M. Evolution of Hoxa11 Regulation in Vertebrates is Linked to the Pentadactyl state // Nature. 2016. 539. 89–92. Doi: 10.1038/Nature19813

2. Leite-Castro J., Beviano V., Rodrigues Pn, Freitas R. Hoxa Genes and the Fin-to-Limb Transition in Vertebrates // J. Dev. Biol. 2016, 4, 10; DOI: 10.3390/JDB4010010