Hemichordates’ diffuse “skin brain” shows unexpected complexity

Hemichordates are close relatives of chordates. Their nervous system patterning is chordate-like, but their neural architecture remains unexplored. A new study in PLOS Biology reveals an unexpected neuroanatomical complexity in these animals, also informing chordate origins.

However, the nature of the neural net and whether it can be homologised to the nerve net in cnidarians or is more akin to a peripheral nervous system has remained unclear.
Another puzzle that emerged from molecular studies of nervous system patterning in hemichordates related to the disparity between molecular coordinates and the underlying anatomy.While the expression of anterior-posterior patterning genes and the position and molecular makeup of brain signalling centres-such as the zona limitans intrathalamica and the isthmic organiser-is strikingly similar between hemichordates and chordates, there is no apparent similarity in the neuroanatomy that develops [5,[8][9][10].
What has been lacking to resolve these long-standing questions is more details of the anatomy of the hemichordate nervous system.Our knowledge of hemichordate neuroanatomy has still largely been based on classic investigations with a resolution that was not sufficient to reveal many individual neurons, neurite paths, or synapses [11].Andrade Lope ´z and colleagues [3] have now utilised a comprehensive set of tools to provide the most complete description of neuroanatomy in the acorn worm Saccoglossus kowalewskii to date.Their work combines conventional histological staining, labelling for neurotransmitter markers, dye filling, and the use of transgenic reporters.These approaches allowed them to characterise the detailed anatomy of several neuron classes, including the location of their soma, the morphology of dendrites and axons, and the distribution of putative synapses.One key finding was that several neuron types exhibit strong anteroposterior and dorsoventral concentrations.For example, several conserved neuropeptides show strong expression at the dorsal proboscis base, suggesting the presence of a neuroendocrine centre possibly releasing neuropeptides into the underlying coelomic fluid or circulatory system.Andrade Lope ´z and colleagues also identified neuron types that distinguish the 2 nerve cords in the trunk.Glutamatergic neurons flank the dorsal cord, whereas histaminergic neurons mark the ventral cord, supporting early observations that the dorsal and ventral cords have different functions [11].Neuronal labelling also revealed the detailed cell morphology of several neuron classes [3].The authors found that the majority of the neurons they labelled were sensory neurons.These have a flask shape, with an apically projecting dendrite, often continuing in a sensory cilium.Some of these, like serotonergic sensory neurons, tiled the entire proboscis and projected posteriorly.Individually labelled neurons showed several varicosities (indicative of synapses) along their axons.Some neurons had very long projections spanning almost the entire body.
Overall, the data suggest a hitherto unseen regionalization and complexity of the hemichordate nervous system.It is likely that the complex molecular regionalisation observed by gene expression analyses [5,8] patterns an underlying distribution of specific neuronal cell types, even if this does not manifest in a macroscopic morphological pattern.Regarding the nerve net, the authors found no evidence that the acorn worm nerve plexus has an organisation like that of the simple nets of cnidarians, with neurons directly synapsing on their immediate neighbours [3].This cautions against homologising the cnidarian, hemichordate, or other nerve plexuses as "nerve nets." The rich anatomical resource also helps to reinterpret early observations of acorn worm behaviour [11].The worms move by the combined action of cilia and muscles.They can burrow in the sediment through the peristaltic action of the proboscis.They also react to light, mechanical, or chemical stimuli.Mechanical stimulation of the trunk can lead to ciliary arrest and reversal.The entire body appears photosensitive, as dissected pieces can contract on illumination [11].The tiling of the body by various sensory neurons with long-range projections suggests a diffuse sensory-motor organisation, controlling muscles and ciliated cells, enabling the pieces to behave as the whole.Autonomous nervous activity seems to be centred in the proboscis, which is also the most active region and affects the movement of the rest of the body [11].This agrees with the new anatomical data, which identify the base of the proboscis as a likely integrative centre [3].
The study by Andrade Lope ´z and colleagues revealed a hidden complexity of nervous system organisation in hemichordates hinting at a complex bilaterian brain under their skin with specific connections formed by a large number of neuron types with specific functions.This should attract new attention to these enigmatic animals and stimulate work on their behaviour, neuronal function, and wiring (connectome), also helping to reconstruct chordate origins.