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  • Review Article
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Chordate roots of the vertebrate nervous system: expanding the molecular toolkit

Key Points

  • The neural plate border region of vertebrate embryos gives rise to the neural crest and cranial placodes. Although the basal chordate amphioxus lacks a neural crest and most placodes, comparisons of developmental gene expression and neuroanatomy indicate that vertebrates built these features on a foundation already present in the common ancestor of amphioxus and vertebrates.

  • In vertebrate embryos, the midbrain–hindbrain boundary region functions as an organizer. Amphioxus has the part of the gene network that positions the midbrain–hindbrain boundary, but lacks the portion that confers organizer properties.

  • Tunicates may have more of the gene network for the midbrain–hindbrain organizer than amphioxus, but diverged rapidly from both other organisms and each other.

  • Evolution of the neural crest, placodes and a midbrain–hindbrain organizer has involved the recruitment of old genes for new functions and an expansion of the molecular toolkit by both genetic and epigenetic means.

  • Expansion of the toolkit occurred in part by two rounds of whole genome duplication followed by preferential retention of gene duplicates coding for transcription factors and proteins involved in signalling pathways.

  • Epigenetic mechanisms including DNA methylation and acetylation, alternative splicing, and gene silencing by miRNAs and siRNAs increase the size of the molecular toolkit. Their roles in development and evolution have only begun to be appreciated.

  • Transposons are major contributors to the evolution of new gene regulatory elements and, when located within introns, can mediate exonization whereby introns are recruited into the mature mRNA.

Abstract

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The vertebrate brain is highly complex with millions to billions of neurons. During development, the neural plate border region gives rise to the neural crest, cranial placodes and, in anamniotes, to Rohon-Beard sensory neurons, whereas the boundary region of the midbrain and hindbrain develops organizer properties. Comparisons of developmental gene expression and neuroanatomy between vertebrates and the basal chordate amphioxus, which has only thousands of neurons and lacks a neural crest, most placodes and a midbrain–hindbrain organizer, indicate that these vertebrate features were built on a foundation already present in the ancestral chordate. Recent advances in genomics have provided insights into the elaboration of the molecular toolkit at the invertebrate–vertebrate transition that may have facilitated the evolution of these vertebrate characteristics.

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Figure 1: Major events in nervous system evolution mapped onto the phylogenetic tree of the chordates.
Figure 2: Migration of neuroblasts from neurogenic placodes in the chick resembles that of ectodermal sensory cells in amphioxus.
Figure 3: Patterns of gene expression in neural plate border region, neural tube and underlying mesendoderm in amphioxus and a generic jawed vertebrate.
Figure 4: Comparison of midbrain–hindbrain gene expression in amphioxus, tunicates, and a generic jawed vertebrate.

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Acknowledgements

The author thanks J. Begbie for critical comments on Figure 2, N.D. Holland for critical comments on the manuscript, R.W. Zeller for the photograph of the ascidian Ciona savignyi and F.H. Morris for the human/mouse chimaera in Figure 1. The author is supported by grants from the National Science Foundation (USA).

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Glossary

Tunicates

The sister group of the vertebrates. Tunicates include the appendicularians or larvaceans, ascidians and the thaliaceans. In phylogenetic analyses, appendicularians typically fall basal to ascidians and thaliaceans, although the branch length is long. The thaliaceans, thought to have evolved from ascidians, include three taxa: doliolids, salps and pyrosomes.

Organizer

An embryonic tissue that, when ectopically transplanted, can redirect the fate of the recipient tissue. Organizers in vertebrate embryos include the dorsal blastopore lip or Spemann's organizer in amphibians and its equivalent in other vertebrate embryos, and the tissue spanning the midbrain–hindbrain boundary.

Rohon-Beard sensory neurons

Large, mechanosensory neurons in the dorsal portion of the spinal cord of larval anamniote vertebrates. They typically degenerate later in development.

Protostomes

One of the two main groups of bilaterally symmetrical animals. The protostomes are divided into the Ecdysozoa, including nematodes and arthropods (insects, spiders, crustaceans and some smaller groups) and the Lophotrochozoa (annelids, molluscs and some smaller groups).

Deuterostomes

One of the two main groups of bilaterally symmetrical animals. The deuterostomes include the Ambulacraria (echinoderms plus hemichordates) and the Chordata or chordates (cephalochordates (amphioxus or lancelets), tunicates and vertebrates).

Direct development

A developmental mode in which the fertilized egg progresses to adult without a drastic metamorphosis. By contrast, the larva of indirect developing organisms is radically different from the adult to which it gives rise to by metamorphosis, often with the loss of most larval tissues.

Nerve net

A de-centralized nervous system consisting of interconnected neurons without a brain. Nerve nets occur in cnidarians (for example, sea anemones, jellyfish and corals) echinoderms and hemichordates.

Ptychoderid hemichordates

Hemichordates include the free-living enteropneusts and the sessile pterobranchs. In phylogenetic analyses based on 18s rDNA, enteropneusts are not monophyletic. Instead, two groups of enteropneusts, the Saxipendiidae and the Harrimaniidae (which includes Saccoglossus kowalevskii) plus the pterobranchs form one clade, which is sister group to the third group of enteropneusts, the Ptychoderidae.

Derived

A derived character is one occurring in a particular lineage of a larger taxon which was not present in the last common ancestor of the larger group. An organism with a number of derived characters can be said to be derived within the group.

Siphon

Tunicates are marine, ciliary feeders. In ascidian tunicates, a current of water is pulled in through the incurrent siphon by cilia around the gill slits. After food particles are filtered out, the water exits through the excurrent siphon.

Cis-regulatory elements

Also known as enhancers. 200–300 bp stretches of non-coding DNA to which trans-acting transcription factors bind (along with their co-factors and/or other interacting molecules) in order to upregulate or downregulate the transcription of a gene on the same strand of DNA.

Transposable elements

DNA sequences that can move within a genome. They include DNA transposons (rolling-circle transposons or Helitrons, cut-and-paste transposons and Mavericks or Polintrons) and retrotransposons (retrovirus-like LTR (long terminal repeat) transposons and non-LTR retrotransposons including LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements)), which transpose through an RNA intermediate.

Exonization

The creation of a new exon by incorporation of intronic sequences into the coding region of a gene.

Purifying selection

Also called stabilizing selection, it is natural selection that tends to maintain the status quo.

Locked nucleic acids

Nucleic acids modified by a methylene bridge connecting the 2′ oxygen of ribose with the 4′ carbon, reducing the conformational flexibility of the ribose. Oligonucleotides containing locked nucleic acids have an increased melting temperature and are useful for in situ hybridizations with short target sequences as in miRNAs or siRNAs.

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Holland, L. Chordate roots of the vertebrate nervous system: expanding the molecular toolkit. Nat Rev Neurosci 10, 736–746 (2009). https://doi.org/10.1038/nrn2703

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