Violations of the regulation of genes by transcription factors: polysyndactyly

Fundamental mechanisms during development

  • Regulation of genes by transcription factors.
  • Intercellular signaling through direct contact and morphogeny.
  • Induction of shape and cell polarity.
  • Moving cells.
  • Programmable cell death.

Regulation of genes by transcription factors

Transcription factors control the development by altering the expression of genes, including other transcription factors. Group functioning together of transcription factors called transcriptional regulatory modules, and the separation of the functions of these modules is an important task for developmental genetics.

Some transcription factors activate target genes, others suppress them. Still other transcription factors have functions as activators and repressors (the so-called bifunctional transcription factors). Regulatory modules control the development, forcing various combinations of transcription factors expressed in different places and at different times, which changes the spatial-temporal development indicators. Directing differential expression of genes in space and in time, a transcription regulatory modules are the Central element in the development of the embryo.

Transcriptional regulatory complex consists of many General transcription factors combine with the specific factors responsible for the selectivity of the transcription complex.

Most of the General transcription factors detected thousands of transcriptional complexes throughout the genome, and although each of them needed, their role in the development of nonspecific. Specific transcription factors are also involved in the formation of complexes of transcription factors, but only in certain cells or at specific times of development, thus providing a fine regulation of gene expression, respectively, of development processes. The importance of transcription factors for normal development seen, for example, unusual mutation Noh D13, causing polysyndactyly — incompletely dominant disease. Heterozygotes have interphalangeal webbed and additional fingers and toes. Rare homozygotes had similar, but more pronounced abnormalities as well as malformations of bones of the hands, wrists, feet and ankles.

Mutation Noh D13, causing polysyndactyly caused by the expansion polulineinogo plot in the N-terminal region of the protein; the normal protein contains 15 alanine residues, and the mutant from 22 to 24 residues. Heterozygosity for mutations with loss of function of the gene Noh D13 has a small influence on the development of the limbs, like a vestigial extra finger between the first and second bones of the Tarsus or between the fourth and fifth tarsal bones of the feet.

The expansion of the alanine that causes polysyndactyly probably uses a mechanism of gain of function. Regardless of the precise mechanism of this disease shows that the overall function of the gene Noh — definition of local matching along the main axis in the course of development.