Establishment of Left–Right Asymmetry in Chick and Mouse Embryos

Yoshihiro Komatsu, University of Texas Health Science Center at Houston, Houston, Texas, USA
Yuji Mishina, University of Michigan, Ann Arbor, Michigan, USA

Published online: July 2014

DOI: 10.1002/9780470015902.a0000727.pub2

Abstract

All vertebrates have consistent left–right structural asymmetry, and deviations from the typical asymmetry in humans are clinically important. Studies elucidating the mechanisms that establish left–right asymmetry have lead to some of the most elegant advances in the field of embryology. In the past several decades, while we have gained an extensive understanding of the development of left–right asymmetry during embryogenesis, many questions remain to be addressed to fully appreciate the molecular mechanisms underlying its establishment. In this review article, the authors summarise the gene regulatory network that controls left–right patterning. They also focus on our current understanding of how left–right symmetry is broken.

Key Concepts:

  • Primary cilia rotating in a clockwise direction generate a unidirectional leftward fluid flow at a structure called the node, resulting in left–right symmetry breakage in mouse embryos. Similar leftward flow is observed in many vertebrate embryos.

  • Planar cell polarity (PCP) signalling, initially identified in the fruitfly, controls the uniform orientation of hairs and bristles on the body.

  • A primary cilium is a microtubule‐based antenna‐like structure lacking the central pairs of microtubules. This ‘9+0’ microtubular structure and lack of dynein arms render them immotile, whereas motile cilia have a ‘9+2’ microtubular structure with dynein arms.

  • BMP signalling negatively regulates cell cycle at the ventral surface of the node.

  • The posterior tilt of nodal cilia regulated by planar cell polarity is critical to generate a unilateral leftward flow from the rotation of the nodal cilia.

  • The ventral surface of the node is quiescent that allows formation of cilia.

Keywords: chick; cilia; gene expression; left–right patterning; mouse; node

Figure 1.

The known left–right cascade of gene activity in chick embryo. (a–d) show four successive stages (see text) as seen in plan view from above, with anterior at top. (a) Primitive streak stage; (b) a short ‘head process’ stage, with mesoderm emerging laterally and ahead of the regressing Hensen's node; (c) a late headfold or neurula stage (about four somites segmenting in mesoderm). Dotted line in (c) showing the level of transverse section in (f); (d) stage with the newly looped heart tube, and onset of embryo torsion (twisting); (e) transverse section through posterior Hensen's node at stage of (b). Note consistent anatomically asymmetrical appearance, as well as gene expressions, in node whose deep structure is in continuity with (upper) epiblast layer. Separate bilateral lower layer is mesoderm; (f) transverse section, ahead of regressed node but posterior to segmented somites, at stage of (c). Colour code for gene expressions: green, Act‐RIIa; blue, Shh; yellow, nodal and red, cSnR. Note that in (f), the lefty genes known from other vertebrates (see text) would occupy a left lateral position similar to nodal but also a narrow domain at the left lateral side of the Shh expression domain at the neural midline (floorplate) above the notochord. Abbreviations: Hn, Hensen's node; nc, notochord; s, somite and h, formed heart tube.

Figure 2.

Autonomy and interference in left–right patterning between twinned axial plans. (a) Shows a plan view from above of a case in which anteriorly opposed streaks have formed by earlier events at near‐opposite sites at a blastular (103–104 cell) stage. The gene expression colours around each node, and corresponding asymmetrical appearance, represent how in such a case each streak autonomously sets up the same, correct left–right asymmetry cascade in relation to its anteroposterior (and dorsoventral) aspects, ruling out prior use of any blastoderm‐wide left–right information (symbolised by double arrowheads from right). (b) Shows a similar view of a case where events initiating streaks were not fully opposed, so that convergence movements of streak development have led them to a more parallel, though separated, conformation. Frequent disturbance or reversal of laterality in just the right‐hand axis of such cases suggests that a preferential gene expression on the right normally first ‘converts’ a molecular chirality aligned in the vicinity of each streak into differential right‐ and left‐specific gene expressions. Right‐hand twin members are thus at risk of abnormal symmetrisation. Colour code for gene expressions: green, Act‐RIIa; blue, Shh; yellow, nodal and red, cSnR.

Figure 3.

Scanning electron microscopic analysis of the node at mouse embryonic day (E) E7.75. (a) Wild‐type mouse embryo shows a cup shaped structure with evenly distributed ciliated cells when viewed from the ventral side. (b) High‐magnification images from (a). At E7.75, around 1–2 µm length of primary cilia (red arrows) is formed in node cells (pit cells).

Figure 4.

Cell cycle quiescence regulates the nodal cilia formation in mouse embryos. Immunohistochemical analysis at E8.0 shows the expression of Ki‐67 (a) and p27Kip1 (b). Tissue section was counterstained by DAPI (c, e). Note that Ki‐67 is not detectable in cells of the ventral surface of node where nodal cilia are developed whereas p27Kip1 is produced exclusively in the ventral surface of node (d). Reproduced from Komatsu et al. (). © The Company of Biologists Ltd.

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Related Sub-Topics:

Determination of Cell Fate | Cleavage and Gastrulation | Genes, Molecules and Cellular Processes
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Article Title: Establishment of Left–Right Asymmetry in Chick and Mouse Embryos
 
How to Cite close
Komatsu, Yoshihiro, and Mishina, Yuji(Jul 2014) Establishment of Left–Right Asymmetry in Chick and Mouse Embryos. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000727.pub2]