Left-right axis development: examples of similar and divergent strategies to generate asymmetric morphogenesis in chick and mouse embryos

Abstract

Left-right asymmetry of internal organs is widely distributed in the animal kingdom. The chick and mouse embryos have served as important model organisms to analyze the mechanisms underlying the establishment of the left-right axis. In the chick embryo many genes have been found to be asymmetrically expressed in and around the node, while the same genes in the mouse show symmetric expression patterns. In the mouse there is strong evidence for an establishment of left-right asymmetry through nodal cilia. In contrast, in the chick and in many other organisms left-right asymmetry is probably generated by an early-acting event involving membrane depolarization. In both birds and mammals a conserved Nodal-Lefty-Pitx2 module exists that controls many aspects of asymmetric morphogenesis. This review also gives examples of divergent mechanisms of establishing asymmetric organ formation. Thus there is ample evidence for conserved and non-conserved strategies to generate asymmetry in birds and mammals.

Laterality defects are influenced by timing of treatments and animal model

“…In the second step, chiral information established in the first step is translated to asymmetric gene expression. Several genes, including nodal, lefty and pitx2, have well characterized asymmetric expression patterns that have been observed in multiple species; the positive- and negative-feedbacks among members of these signaling pathways are well understood (Burdine and Schier, 2000; Schlueter and Brand, 2007; Duboc and Lepage, 2008). Finally, in the third step, information from asymmetric gene expression is amplified and transmitted to several organ systems, and differential migration, proliferation, tension, and adhesion of cells allows for asymmetric development and position of organs (Yost, 1991; Yost, 1992; Gros et al, 2009; Tabin, 2006).…”

Consistent left-right asymmetry cannot be established by late organizers inXenopusunless the late organizer is a conjoined twin

“…While the degree of evolutionary conservation is far from clear (Levin, 2006;Okumura et al, 2008;Schlueter and Brand, 2007), these mechanisms have been worked out in the most detail in Xenopus embryos. The development of normal LR asymmetry in Xenopus embryos requires four specific ion transporters: two H + pumps, V-ATPase (Adams et al, 2006) and H,K-ATPase (Levin et al, 2002), and two K + channels, KvLQT-1 (Morokuma et al, 2008) and K atp (Chen and Levin, 2004).…”

A right-sided pathway involving FGF8 / Snai1 controls asymmetric development of the proepicardium in the chick embryo

“…This pathway might be of general relevance for setting up L-R asymmetries at the venous pole of the heart. left-right asymmetry ͉ Tbx18 ͉ Pitx2 ͉ venous pole morphogenesis T he left-right (L-R) axis controls asymmetric organogenesis in vertebrates (1)(2)(3). In lower chordates, Xenopus, and chick, breaking of the initial bilateral body symmetry involves the asymmetric distribution of ion channels and transporters, resulting in the development of membrane potential differences between the left and right body side, which may drive an asymmetric transport of small molecules through gap junctions (4,5).…”

“…In mammals, this nodal flow is believed to be the sole mechanism by which L-R asymmetry is initiated (7). In the chicken embryo, asymmetric gene expression in Hensen's node of gastrula stage embryos is an important intermediate step of establishing L-R asymmetry (2). Shh, for example, is asymmetrically expressed on the left side of Hensen's node and induces Nodal expression in a small left-sided domain adjacent to Hensen's node (8).…”