Nodal

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Nodal or NODAL is a protein that is encoded in humans by the NODAL gene , which is located on the long arm of chromosome 10 ( gene locus 10q22.1). As a signal protein, Nodal is one of the cytokines from the TGF-β superfamily of growth and differentiation factors.

The human NODAL is homologous to the Nodal (354 AA ) encoded by the mouse gene Nodal . It is a 347 amino acid long polypeptide , which in the human cell - as well as in the mouse by cleavage of the 110 AS long C-terminal end - to a precursor protein of processed is out of the turn, which is 26 formed AS long actual signal peptide by cleavage, which differs from the mouse of the same length in its amino acid sequence . This short peptide can be secreted into the extracellular environment and then acts as a signal (signal transfer) on cells receptive to it in the vicinity.

As a cytokine homologous, Nodal plays an important role in human ontogenetic development because it is involved in the development of the left-right asymmetry for the location of organs, such as the heart.

It is found in a similar function not only in other species of vertebrates ( vertebrates ), but also in other chordates ( chordata ), both skullless and tunicates , as well as in other new mouths ( deuterostomia ), such as echinoderms ; In addition, it was found within the trunk group of the primordial mouths ( Protostomia ) in snails - but not in the nematode C. elegans and in the arthropod Drosophila - which also belong to the subdivision of bilaterals ( Bilateria ) in the realm of multicellular animals ( Metazoa ).

During the very early embryogenesis , in the third week of development, the (anterior-posterior) longitudinal axis of the body for the human germ is self-organized by the primitive knot as the morphogenetic organizer. These (nodal) cells at the front end of the primitive stripe form signaling substances and distribute them from the primitive pit via the flow in the extraembryonic fluid generated by them through the rotation of the cilia . Since each of the monocilia rotates with the same direction of rotation and all are inclined in the same direction (towards posterior), this results in a directed flow (seen from the dorsal, counterclockwise), even with only two cilia. Therefore, other cells may be the outer seed layer of these signals are dependent on the direction different reached and different reply NODAL is produced by cells on one side of significantly stronger expressed than on the other side (by which further steps initiated induces be), which later for the asymmetric position of some organs lead in the bilateral organism. If the direction of flow is reversed, their position is reversed ( situs inversus ).

In addition, NODAL also plays a role in other steps in the development process, for example in the formation of patterns and differentiations in the neural tissue, which can also be different in different species.

Notes and individual references

  1. ↑ On the spelling: The names, short names and symbols of genes are - if it is necessary, as in this context, to distinguish between gene and gene product - following the conventions in italic font, those of proteins are not; capital letters are common for humans.
  2. ↑ a b see entry UniProtKB - Q96S42 (NODAL_HUMAN) in the bioinformatic database for proteins UniProt .
  3. ↑ S. Nonaka, Y. Satoko, W. Daisuk, I. Shingo, G. Tomonobu, M. Wallace, H. Hamada: De Novo Formation of Left-Right Asymmetry by Posterior Tilt of Nodal Cilia . In: PLoS Biology . Volume 3, No. 8, August 2005, p. 268. doi : 10.1371 / journal.pbio.0030268 . PMID 16035921 .
  4. ↑ K. Shinohara, A. Kawasumi, A. Takamatsu, S. Yoshiba, Y. Botilde, N. Motoyama, W. Reith, B. Durand, H. Shiratori, H. Hamada: Two rotating cilia in the node cavity are sufficient to break left-right symmetry in the mouse embryo . In: Nature Communications . Volume 3, January 2012, p. 622. doi : 10.1038 / ncomms1624 . PMID 22233632 .
  5. ↑ N. Hirokawa, Y. Tanaka, Y. Okada, S. Takeda: Nodal flow and the generation of left-right asymmetry . In: Cell . Volume 125, No. 1, April 2006, pp. 33-45. doi : 10.1016 / j.cell.2006.03.002 . PMID 16615888 .
  6. ^ S. Nonaka: Modification of mouse nodal flow by applying artificial flow . In: Methods in Cell Biology . Volume 91, December 2009, pp. 287-297. doi : 10.1016 / S0091-679X (08) 91015-3 . PMID 20409792 .

literature

  • W. Janning, E. Knust: Genetics . Thieme, Stuttgart 2008, ISBN 978-3-13-128772-4 , Chapter 30.2 Formation of the left-right asymmetry, p. 461ff.
  • C. Brokaw: Symmetry breaking in a model for nodal cilia . Library Caltech, Pasadena, 2005, pdf .