Abstract
BackgroundNodal is an important determinant of the left-right (LR) body axis in bilaterians, specifying the right side in protostomes and non-chordate deuterostomes as opposed to the left side in chordates. Amphioxus represents an early-branching chordate group, rendering it especially useful for studying the character states that predate the origin of vertebrates. However, its anatomy, involving offset arrangement of axial structures, marked asymmetry of the oropharyngeal region, and, most notably, a mouth positioned on the left side, contrasts with the symmetric arrangement of the corresponding regions in other chordates.ResultsWe show that the Nodal signaling pathway acts to specify the LR axis in the cephalochordate amphioxus in a similar way as in vertebrates. At early neurula stages, Nodal switches from initial bilateral to the left-sided expression and subsequently specifies the left embryonic side. Perturbation of Nodal signaling with small chemical inhibitors (SB505124 and SB431542) alters expression of other members of the pathway and of left/right-sided, organ-specific genes. Upon inhibition, larvae display loss of the innate alternation of both somites and axons of peripheral nerves and loss of left-sided pharyngeal structures, such as the mouth, the preoral pit, and the duct of the club-shaped gland. Concomitantly, the left side displays ectopic expression of otherwise right-sided genes, and the larvae exhibit bilaterally symmetrical morphology, with duplicated endostyle and club-shaped gland structures.ConclusionsWe demonstrate that Nodal signaling is necessary for establishing the LR embryonic axis and for developing profound asymmetry in amphioxus. Our data suggest that initial symmetry breaking in amphioxus and propagation of the pathway on the left side correspond with the situation in vertebrates. However, the organs that become targets of the pathway differ between amphioxus and vertebrates, which may explain the pronounced asymmetry of its oropharyngeal and axial structures and the left-sided position of the mouth.Electronic supplementary materialThe online version of this article (doi:10.1186/2041-9139-6-5) contains supplementary material, which is available to authorized users.
Highlights
Nodal is an important determinant of the left-right (LR) body axis in bilaterians, specifying the right side in protostomes and non-chordate deuterostomes as opposed to the left side in chordates
Asymmetric expression of developmental regulatory genes across the left-right axis during amphioxus embryogenesis and larval development To establish whether cephalochordates use a conserved genetic network for LR patterning, we first surveyed the expression patterns of amphioxus homologs of the Nodal signaling cascade and genes known to be responsible for vertebrate LR asymmetric development
We have shown here that Nodal signaling is responsible for establishment of the bilateral asymmetry of amphioxus paraxial structures, reminiscent of the role of Nodal in LR asymmetry on the pharyngeal region
Summary
Nodal is an important determinant of the left-right (LR) body axis in bilaterians, specifying the right side in protostomes and non-chordate deuterostomes as opposed to the left side in chordates. Bilaterians exhibit varying degrees of asymmetry along the left-right (LR) body axis. A transforming growth factor beta (TGF-β) superfamily factor, has been previously identified to be central to determining LR asymmetry through unilateral activation of downstream genes. Nodal activates its own expression and triggers expression of the TGF-β factor Lefty and transcription factor Pitx. Pitx subsequently triggers expression of downstream targets and promotes tissue-specific proliferation and differentiation, leading to asymmetrical development of the affected organs ([14] and literature therein)
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