Amphioxus: The invertebrate that can model for vertebrates

I know you came here to learn about amphioxus, but first, a song. This song was regularly taught to undergrads at various universities in the past (see history here), new articles suggest that it may be wrong! Keep reading to find out more about what’s right, what’s wrong, and what we can learn about vertebrate development from an invertebrate.

Background

Amphioxus is named for the Greek for “both ends pointed” and are animals found in warm oceans mainly buried in the sand.

The lancelets retain all normal chordate features, including dorsal nerve cord with support from a notochord, gill slits, myomeres for muscular structure, and a post-anal tail. Their relationship with vertebrates makes them an excellent animal model; however, they don’t have true vertebral features and lack a true vertebrate and have poorly developed brains.

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Figure 1. An amphioxus. Holland et al. 2015.

Previous work on invertebrates has yielded crucial information for developmental biology and the understanding of conserved signal cascades. A main reason that invertebrates are so elucidative is their smaller genome size with decreased duplication. This allows the easier identification of genes that are evolutionary conserved. However, this approach is challenging to translate to vertebrates, highlighting the need to have a vertebrate model with a “relatively unduplicated genome” (Holland et al. 2015). Chordates occupy this niche as a “proxy for the ancestral vertebrate”(Holland et al. 2015), specifically lancelets and amphioxus, because they share certain features including kidneys and segmental paraxial muscles.

Conservation and amphioxus as a model

The structure of the amphioxus tail bud has been related to the development of the vertebrate tail bud. Both organisms generate the neural tube, somites, and posterior portions of the notochord. The development of the tail bud is controversial, as it is unclear whether it is a continuation of gastrulation or is separate from the formation of the trunk. The latter view was established in studies on chicks and mice, with the results suggesting that the tail bud is a blastema of pluripotent mesenchymal cells. This means the tail bud retains the ability to differentiate into multiple tissues. The other side of the argument is derived from the use of frogs as a model organism, which shows that the tail bud is pre-partioned and an extension of gastrulation. Amphioxus gastrulation process is thought to reflect the fundamental processes in vertebrates because it is widely accepted that vertebrates are derived from an amphioxus-like ancestor with “relatively small, non-yolky eggs” (Holland et al. 2015). Several genes, including Wnts are preserved and expressed in the tail buds of both vertebrates and amphioxus (see Figure 2 below). The expression of these Wnts can compensate for each other, with their genes being partially overlapped in ampioxus and xenopus. These genes are responsible for tail elongation and tail formation. The conserved interaction of these genes suggests that amphoxious structures can offer insight for vertebrate homologs.

Figure 5.

Figure 2. Gene expression in amphioxus bud development. Holland et al. 2015.

Similarly, the pharynx formation of amphioxus offers unique insight to the role of endoderm and neural crest in vertebrates. Primarily, amphioxus do not have neural crests or derivatives, allowing separation between what is caused due to pharyngeal endoderm patterning and what is neural crest. When amphioxus were exposed to retinoic acid, the same chemical that is in Accutane and causes craniofacial birth defects when taken early in pregnancy, they expressed a similar phenotype. This defect has also been exhibited in mice, chicks, and quail, with its cause identified as the retinoic acid shifting the pharynx anteriorly. The affected downstream genes are in the Pax family, and the amphioxus genome has no duplication in this region. Both amphioxus and vertebrates expressed Pax1 and Pax9 genes in their pharyngeal endoderm, exhibiting roles in the prevention of tissue fusion and promoting cell proliferation.

The final morphological element of invertebrate development that can be examined through the use of amphioxus as a model organism is neural crest formation. This is an interesting use of an amphioxus, as they do not have a neural crest! The neurulation, however, is related to several vertebrates including frogs, birds, and mammals; this conserved process is the formation of the dorsal ectoderm into a neural plate. This conserved gene patterning between an organism that does not form a neural crest and one that does has raised questions about the true function of these genes. The answer to these inconsistencies are accounted by the location of the gene expression, like the FoxD gene which is expressed in the edges of the non-neural plate of amphioxus and in the neural crest of vertebrates.

Genetic experiments in amphioxus are inhibited by the lack of continuous breeding, currently, but this element is rapidly changing. While there are obvious differences in the actual processes, certain elements are easily translatable, making a simply invertebrate easily translatable in the lab. The amphioxus model has several benefits not explained here (but is mentioned in the article that this is based on) including the importance of the implications of the use of amphioxus as a genomic model and the evolution of processes throughout increasing species complexity.

Wnts in amphioxus and vertebrate appendage development

The use of amphioxus to determine the evolution of Wnt-roles in vertebrate appendage development has shown that the AmphiTbx4/5 gene has evolved into the Tbx4 and Tbx5 genes, which are responsible for limb acquisition. Existing research has suggested that there is a strong relationship between the formation of the amphioxus and vertebral tail buds. Wnt expression around the formation of these buds varies between the two organisms, but Wnts can compensate for each other in the same pathway, explaining evolved variation. Figure 4 (below) shows that the TBx4/5 gene from amphioxus can rescue limb growth in a mouse with a conditional knockout of Tbx5. This indicates that the Tbx4/5 gene has been evolutionarily preserved in the progression from invertebrate to vertebrate. The explanation of the separation of regulation behind this development can be shown in Figure 5 below (Minguillon et al. 2009).

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Figure 5. This image shows the locations of Tbx4/5 compared to Tbx 4 and Tbx 5 in fish and amphioxus. Minguillon et al. 2009.

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Figure 4. A’-C’ show the rescued phenotype of mouse forelimb development. Minguillon et al. 2009.

 

 

 

 

 

 

 

 

 

Why do we care?

The amphioxus is a rising model organism for vertebrate development. We’ve seen that the Wnt and Tbx pathways are conserved through evolution, hinting that amphioxus has potential for a laboratory model organism.  Here is another video explaining some more reasoning behind this model organism:

So maybe it isn’t actually “A Long Way From Amphioxus” after all.

Weaknesses in the paper

The body was incredibly extensive, but the conclusion left a lot to be desired. Because the paper is a review paper, however, this is a common error. Additionally, the primary paper discussed is a review that lacks obvious quantitative data.

References

Holland, L., Laudet, V., & Schubert, M. (n.d.). The chordate amphioxus: An emerging model organism for developmental biology. Cellular and Molecular Life Sciences. Retrieved March 13, 2015, from http://www.ncbi.nlm.nih.gov/pubmed/15378201

“It’s a Long Way from Amphioxus.” YouTube. Ed. AWisconsinBestiary. YouTube, 16 Feb. 2014. Web. 26 Apr. 2015.

Minguillon, C., Gibson-Brown, J. J., & Logan, M. P. (2009). Tbx4/5 gene duplication and the origin of vertebrate paired appendages. Proceedings of the National Academy of Sciences of the United States of America, 106(51), 21726–21730. doi:10.1073/pnas.0910153106

 

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