Human pathology

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ventral node

Hansen node

The establishment of left-right asymmetry in mammals is a good example of how multiple cell biological processes coordinate in the formation of a basic body plan.

The leftward movement of fluid at the ventral node, called nodal flow, is the central process in symmetry breaking on the left-right axis.

Nodal flow is autonomously generated by the rotation of cilia that are tilted toward the posterior on cells of the ventral node. These cilia are built by transport via the KIF3 motor complex.

How nodal flow is interpreted to create left-right asymmetry has been a matter of debate.

The leftward movement of membrane-sheathed particles, called nodal vesicular parcels (NVPs), may result in the activation of the non-canonical Hedgehog signaling pathway, an asymmetric elevation in intracellular Ca(2+) and changes in gene expression.

Three steps for L-R assymetry

- step 1: initial break of symetry
- step 2: asymmetric expression in LPM
- step 3: asymmetric organ morphogenesis

Pathology

Three steps for L-R assymetry and mutated gene in humans

- step 1: initial break of symetry: DNAI1, DNAH5, DNAH1 (LRD), INVS
- step 2: asymmetric expression in LPM: CFC1, LEFTYA, ACVR2B, CFC1-NODAL +/-,
- step 3: asymmetric organ morphogenesis

See also

- nodal flow

References

- Tian T, Meng AM. Nodal signals pattern vertebrate embryos. Cell Mol Life Sci. 2006 Mar;63(6):672-85. PMID: 16465442

- Hirokawa N, Tanaka Y, Okada Y, Takeda S. Nodal flow and the generation of left-right asymmetry. Cell. 2006 Apr 7;125(1):33-45. PMID: 16615888