Opposing Nodal/Vg1 and BMP signals mediate axial patterning in embryos of the basal chordate amphioxus

Onai, Takayuki; Yu, Jr-Kai; Blitz, Ira L.; Cho, Ken W.Y.; Holland, Linda Z.

doi:10.1016/j.ydbio.2010.05.016

Cited by 81 publications

(160 citation statements)

References 100 publications

(139 reference statements)

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“…This suggests that the role of the FGF signal in mesoderm and neural induction was acquired in the chordate lineage after cephalochordate divergence. These results lead us to propose that the "default model" could be applied to amphioxus, supported by the fact that activation of the BMP signaling pathway in amphioxus is sufficient to abolish neural induction (22,23).…”

Section: Discussion Evolution Of the Fgf Gene Family Inmentioning

confidence: 94%

Amphioxus FGF signaling predicts the acquisition of vertebrate morphological traits

Bertrand

Camasses

Somorjai

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

102

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FGF signaling is one of the few cell-cell signaling pathways conserved among all metazoans. The diversity of FGF gene content among different phyla suggests that evolution of FGF signaling may have participated in generating the current variety of animal forms. Vertebrates possess the greatest number of FGF genes, the functional evolution of which may have been implicated in the acquisition of vertebrate-specific morphological traits. In this study, we have investigated the roles of the FGF signal during embryogenesis of the cephalochordate amphioxus, the best proxy for the chordate ancestor. We first isolate the full FGF gene complement and determine the evolutionary relationships between amphioxus and vertebrate FGFs via phylogenetic and synteny conservation analysis. Using pharmacological treatments, we inhibit the FGF signaling pathway in amphioxus embryos in different time windows. Our results show that the requirement for FGF signaling during gastrulation is a conserved character among chordates, whereas this signal is not necessary for neural induction in amphioxus, in contrast to what is known in vertebrates. We also show that FGF signal, acting through the MAPK pathway, is necessary for the formation of the most anterior somites in amphioxus, whereas more posterior somite formation is not FGF-dependent. This result leads us to propose that modification of the FGF signal function in the anterior paraxial mesoderm in an amphioxus-like vertebrate ancestor might have contributed to the loss of segmentation in the preotic paraxial mesoderm of the vertebrate head.O nly a few cell-cell signaling molecules are known to play a major role during metazoan embryonic development. Among them, the FGFs were discovered in the mid-1970s in vertebrates. FGFs are small proteins, generally secreted, characterized by a conserved functional domain and acting through binding to their transmembrane receptors [FGF receptors (FGFRs)], causing them to homodimerize. This leads to intracellular autophosphorylation and further activation of cytoplasmic signaling cascades, such as the MAPK and the PI3K pathways (1).Sequencing of several complete metazoan genomes has shown that FGF and FGFR genes were already present in the common ancestor of diploblastic and bilaterian animals (2). In vertebrates, at least 22 genes coding for FGFs and 4 coding for their FGFRs are known. In contrast, only 3 genes coding for FGFs and 2 coding for FGFRs have been described in Drosophila (2). In the urochordate Ciona intestinalis, a member of the sister group of vertebrates, only 6 FGF genes are present, for which some orthology relationships with vertebrate FGFs are still not resolved (3). This large number of FGFs and FGFRs in vertebrates raises the question of their implication in the evolution of vertebrate-specific morphological characteristics.In vertebrates, FGF signaling is involved in different developmental processes, among which are neural and mesoderm induction in the early embryo, and somitogenesis and limb bud formation at later stages (4)....

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Section: Discussion Evolution Of the Fgf Gene Family Inmentioning

confidence: 94%

Amphioxus FGF signaling predicts the acquisition of vertebrate morphological traits

Bertrand

Camasses

Somorjai

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

102

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“…Cer, Nodal, Lefty, and Pitx are known to be asymmetrically expressed in amphioxus embryos (18)(19)(20)(21), however the relative timing of their expression has yet to be elucidated. We therefore examined whether these genes are spatiotemporally activated in patterns consistent with a regulatory hierarchy.…”

Section: Resultsmentioning

confidence: 99%

Cerberus–Nodal–Lefty–Pitx signaling cascade controls left – right asymmetry in amphioxus

Liu

Xing

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Many bilaterally symmetrical animals develop genetically programmed left-right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left-right asymmetry as a larva. We show that Cerberus, Nodal, Lefty, and their target transcription factor Pitx are sequentially activated in amphioxus embryos. We then address their function by transcription activator-like effector nucleases (TALEN)-based knockout and heat-shock promoter (HSP)-driven overexpression. Knockout of Cerberus leads to ectopic right-sided expression of Nodal, Lefty, and Pitx, whereas overexpression of Cerberus represses their left-sided expression. Overexpression of Nodal in turn represses Cerberus and activates Lefty and Pitx ectopically on the right side. We also show Lefty represses Nodal, whereas Pitx activates Nodal. These data combine in a model in which Cerberus determines whether the left-sided gene expression cassette is activated or repressed. These regulatory steps are essential for normal left-right asymmetry to develop, as when they are disrupted embryos may instead form two phenotypic left sides or two phenotypic right sides. Our study shows the regulatory cassette controlling left-right asymmetry was in place in the ancestor of amphioxus and vertebrates. This includes the Nodal inhibitors Cerberus and Lefty, both of which operate in feedback loops with Nodal and combine to establish asymmetric Pitx expression. Cerberus and Lefty are missing from most invertebrate lineages, marking this mechanism as an innovation in the lineage leading to modern chordates.B ilaterians share three primary developmental axes. The anterior-posterior (AP) and dorsal-ventral (DV) axes define bilaterally symmetrical organization. The third axis, orthogonal to these, is known as the medial-lateral or left-right (LR) axis and displays mirror-image symmetry. However, many bilaterian species deviate consistently from true symmetry, raising fundamental questions of how symmetry is broken and how different developmental programs can unfold on the left and right sides of an organism (1). In vertebrates, this includes asymmetric development of the heart and viscera, disruption of which during embryogenesis causes a range of human disorders (2).Correct LR organization in vertebrates is regulated by a gene cassette in which right-sided Cerberus (Cer) and left-sided Nodal and Lefty regulate left-sided expression of the Pitx family gene Pitx2 and hence morphological LR asymmetry (3). Cer expression on the right of the embryonic node is required to repress Nodal signaling, which happens by Cer protein binding directly to Nodal protein. This restricts the ability of Nodal protein to activate the expression of the Nodal gene, leading to an up-regulation of Nodal on the left of the embryo. Lefty expression is also up-regulated by Nodal and, like Cer, acts as an extracellular inhibitor of Nodal. Coexpression o...

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“…In addition, ascidian embryos do not possess an organizer region on the circum-notochord side, which is critical for the development of vertebrate embryos. On the other hand, cephalochordate embryos also have an organizer on the circum-notochord side secreting a BMP antagonist (Yu et al, 2007;Onai et al, 2010). Thus, the molecular strategies leading to the similar fate maps appear to be more diverse than was suspected hitherto, suggesting that organisms could generate the same fate map and eventually the same body plan while developing along divergent routes.…”

Section: Comparison Of Tunicate Fate Maps With Those Of Vertebratesmentioning

confidence: 99%

An Advanced Filter-Feeder Hypothesis for Urochordate Evolution

Satoh

2009

Zoological Science

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Opposing Nodal/Vg1 and BMP signals mediate axial patterning in embryos of the basal chordate amphioxus

Cited by 81 publications

References 100 publications

Amphioxus FGF signaling predicts the acquisition of vertebrate morphological traits

Amphioxus FGF signaling predicts the acquisition of vertebrate morphological traits

Cerberus–Nodal–Lefty–Pitx signaling cascade controls left – right asymmetry in amphioxus

An Advanced Filter-Feeder Hypothesis for Urochordate Evolution

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