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J. Cardiovasc. Dev. Dis. 2018, 5(1), 1; https://doi.org/10.3390/jcdd5010001

Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us?

Institute of Zoology, University of Hohenheim, 70593 Stuttgart, Germany
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Received: 11 December 2017 / Revised: 25 December 2017 / Accepted: 25 December 2017 / Published: 29 December 2017
(This article belongs to the Special Issue Left–Right Asymmetry and Cardiac Morphogenesis)
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Abstract

Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure. View Full-Text
Keywords: left-right asymmetry; symmetry breaking; cilia; Nodal; leftward flow; left-right organizer; Nodal cascade; heterotaxia; situs ambiguus; situs inversus left-right asymmetry; symmetry breaking; cilia; Nodal; leftward flow; left-right organizer; Nodal cascade; heterotaxia; situs ambiguus; situs inversus
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Schweickert, A.; Ott, T.; Kurz, S.; Tingler, M.; Maerker, M.; Fuhl, F.; Blum, M. Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us? J. Cardiovasc. Dev. Dis. 2018, 5, 1.

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