Despite their differences, vertebrates, worms and insects are all believed to be descended from a common ancestor – a worm-like organism, named Urbilateria, which lived some 600 million years ago. Urbilateria displayed bilateral symmetry – its body was symmetrical along its longitudinal axis – and this body plan was inherited by the diverse array of organisms descended from it. But, according to new research, just published in the journal Cell, it wasn’t just bilateral symmetry that Urbilateria’s descendants inherited: at the earliest stages of their evolution, vertebrates – including humans – may have inherited the organization of their nervous systems from Urbilateria as well.
The simplest nervous systems lack a “brain”, and instead consist of diffuse networks of nerves. The nervous systems of vertebrates and annelid worms, however, are organized in another way, with nerve fibres arranged in centralized cords, and large groups of nerve cells (called ganglia, singular ganglion). The major differences between them are, of course, the level of complexity, and the positioning – the nerve cord of invertebrates is located ventrally (toward the belly), whereas the vertebrate spinal cord is located dorsally (toward the back). In 1875, Anton Dohrn proposed the “annelid” theory, according to which, the vertebrate central nervous system arose after a proto-vertebrate inverted itself along the dorsal-ventral axis. This conflicts with the view that the vertebrate and invertebrate nervous systems evolved separately, on the dorsal and ventral sides of the body, respectively.
During vertebrate development, different types of neurons are generated in a specific pattern across the dorso-ventral axis, as well as along the anterior-posterior (longitudinal) axis, of the neural tube (the early developing nervous system). This pattern is brought about by the differential expression of genes encoding diffusible chemical signals. The concentration of a signal in a given location specifies a spatial domain within which a particular type of neuron will be generated. Each domain contains undifferentiated cells that express a unique combination of these chemical signals. The combination of signals in a domain constitutes a “molecular fingerprint” that determines the differentiation pathway of cells within that domain. Each signal is a transcription factor – it binds to DNA and switches a specific gene or set of genes on or off (and each is itself regulated by a diffusible signalling factor belonging to the BMP protein family). This drives the differentiation of the cell along a particular pathway. In this way, sensory neurons are generated in the dorsal half of the neural tube, and motor neurons are generated more ventrally.
In the new study, Detlev Arendt and his colleagues, of the European Molecular Biology Laboratory in Germany, determined the patterns of these developmental signals in the marine ragworm, Platynereis dumerilii (above), and compared them with the patterns found in development of the zebrafish, which is a vertebrate. The genes encoding the annelid versions of three proteins known to be involved in dorso-ventral patterning of the vertebrate nervous system (Nk2.2, Pax6 and Msx) were fused with genes encoding fluorescent proteins, and the constructs were inserted into worm larvae. Confocal microscopy was then used to visualize the gene expression patterns – the molecular fingerprints in each part of the D-V axis. It was found that the developing nervous system of the ragworm, just like that of the zebrafish and other vertebrates, is subdivided into discrete domains, each of which is characterized by the same molecular fingerprint as its counterpart in the zebrafish. Thus, in the ragworm, as in vertebrates, one combination of signals generates motor neurons near the ventral midline, another generates sensory neurons near the dorsal midline, and a third generates interneurons in between. Furthermore, the chemical signals in the ragworm were found to be sensitive to the same regulatory factors that are involved in patterning the dorso-ventral axis of the neural tube of the zebra fish and other vertebrates. They locally increased the concentration of a member of the BMP family; this inhibited expression of the chemical signals that would normally be found in the targetted domain, changing the fingerprint of the cells in that domain and the pattern of cell types acorss the dorso-ventral axis.
There are, of course, no Urbilateria fossils in which these gene expression patterns can be investigated. But Platynereis is considered to be a “living fossil”, and, as such, is thought to resemble the common ancestor more closely than any other extant organism. The study by Arendt’s group therefore supports Dohrn’s annelid theory by providing evidence that vertebrates, worms and insects all inherited their central nervous system from their common ancestor, Urbilateria. But Chris Lowe, an assistant professor in the University of Chicago’s Department of Organismal Biology and Anatomy, has evidence that suggests otherwise. Lowe works with another descendant of Urbilateria, a worm whose nervous system consists of a diffuse network of cells (unlike vertebrates and Platynereis, in which the nervous system is centralized). He points out that this animal uses the same signals as vertebrates for patterning the anterior-posterior axes, even though its nervous system is organized in a different way. So, in Urbilateria, central nervous system development and axis patterning could well have been separate mechanisms that evolved independently.
“Such a complex arrangement could not have been invented twice throughout evolution. It must be the same system,” says co-author Gáspár Jékely. For him, and other members of Arendt’s lab, the question is: how did the inversion from ventral to dorsal take place? According to Dohrn, the ventral-to-dorsal relocation of the central nervous system was simply the result of an inversion of the entire body, so that the belly became the back, and vice versa, after which gill slits nearest the front of the body formed a mouth. Arendt suggests another possibility – that Urbilateria went from being a burrowing worm that spent much of its life partially buried in the seabed to a free-swimming one. With this adaptive change in lifestyle, the pioneer of the vertebrate lineage would have been surrounded by water in all directions, and the body would have been fixed in a new belly-up orientation.
Denes, A. S., et al. (2007). Molecular architecture of annelid nerve cord supports common origin of nervous system centralization in Bilateria. Cell 129: 277-288. [Abstract]