Functional and ultrastructural analysis of reafferent mechanosensation in larval zebrafish.

All animals need to differentiate between exafferent stimuli, which are caused by the environment, and reafferent stimuli, which are caused by their own movement. In the case of mechanosensation in aquatic animals, the exafferent inputs are water vibrations in the animal's proximity, which need to be distinguishable from the reafferent inputs arising from fluid drag due to locomotion. Both of these inputs are detected by the lateral line, a collection of mechanosensory organs distributed along the surface of the body. In this study, we characterize in detail how hair cells-the receptor cells of the lateral line-in zebrafish larvae discriminate between such reafferent and exafferent signals. Using dye labeling of the lateral line nerve, we visualize two parallel descending inputs that can influence lateral line sensitivity. We combine functional imaging with ultra-structural EM circuit reconstruction to show that cholinergic signals originating from the hindbrain transmit efference copies (copies of the motor command that cancel out self-generated reafferent stimulation during locomotion) and that dopaminergic signals from the hypothalamus may have a role in threshold modulation, both in response to locomotion and salient stimuli. We further gain direct mechanistic insight into the core components of this circuit by loss-of-function perturbations using targeted ablations and gene knockouts. We propose that this simple circuit is the core implementation of mechanosensory reafferent suppression in these young animals and that it might form the first instantiation of state-dependent modulation found at later stages in development.

Evolution of sensory systems.

Sensory systems evolve and enable organisms to perceive their sensory Umwelt, the unique set of cues relevant for their survival. The multiple components that comprise sensory systems - the receptors, cells, organs, and dedicated high-order circuits - can vary greatly across species. Sensory receptor gene families can expand and contract across lineages, resulting in enormous sensory diversity. Comparative studies of sensory receptor function have uncovered the molecular basis of receptor properties and identified novel sensory receptor classes and noncanonical sensory strategies. Phylogenetically informed comparisons of sensory systems across multiple species can pinpoint when sensory changes evolve and highlight the role of contingency in sensory system evolution.

Early origin of sweet perception in the songbird radiation.

Early events in the evolutionary history of a clade can shape the sensory systems of descendant lineages. Although the avian ancestor may not have had a sweet receptor, the widespread incidence of nectar-feeding birds suggests multiple acquisitions of sugar detection. In this study, we identify a single early sensory shift of the umami receptor (the T1R1-T1R3 heterodimer) that conferred sweet-sensing abilities in songbirds, a large evolutionary radiation containing nearly half of all living birds. We demonstrate sugar responses across species with diverse diets, uncover critical sites underlying carbohydrate detection, and identify the molecular basis of sensory convergence between songbirds and nectar-specialist hummingbirds. This early shift shaped the sensory biology of an entire radiation, emphasizing the role of contingency and providing an example of the genetic basis of convergence in avian evolution.

Erratum: A novel mechanism for mechanosensory-based rheotaxis in larval zebrafish.

This corrects the article DOI: 10.1038/nature23014.

A novel mechanism for mechanosensory-based rheotaxis in larval zebrafish.

When flying or swimming, animals must adjust their own movement to compensate for displacements induced by the flow of the surrounding air or water. These flow-induced displacements can most easily be detected as visual whole-field motion with respect to the animal's frame of reference. Despite this, many aquatic animals consistently orient and swim against oncoming flows (a behaviour known as rheotaxis) even in the absence of visual cues. How animals achieve this task, and its underlying sensory basis, is still unknown. Here we show that, in the absence of visual information, larval zebrafish (Danio rerio) perform rheotaxis by using flow velocity gradients as navigational cues. We present behavioural data that support a novel algorithm based on such local velocity gradients that fish use to avoid getting dragged by flowing water. Specifically, we show that fish use their mechanosensory lateral line to first sense the curl (or vorticity) of the local velocity vector field to detect the presence of flow and, second, to measure its temporal change after swim bouts to deduce flow direction. These results reveal an elegant navigational strategy based on the sensing of flow velocity gradients and provide a comprehensive behavioural algorithm, also applicable for robotic design, that generalizes to a wide range of animal behaviours in moving fluids.

Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ.

Organ formation requires the precise assembly of progenitor cells into a functional multicellular structure. Mechanical forces probably participate in this process but how they influence organ morphogenesis is still unclear. Here, we show that Wnt11- and Prickle1a-mediated planar cell polarity (PCP) signalling coordinates the formation of the zebrafish ciliated laterality organ (Kupffer's vesicle) by regulating adhesion properties between organ progenitor cells (the dorsal forerunner cells, DFCs). Combined inhibition of Wnt11 and Prickle1a reduces DFC cell-cell adhesion and impairs their compaction and arrangement during vesicle lumen formation. This leads to the formation of a mis-shapen vesicle with small fragmented lumina and shortened cilia, resulting in severely impaired organ function and, as a consequence, randomised laterality of both molecular and visceral asymmetries. Our results reveal a novel role for PCP-dependent cell adhesion in coordinating the supracellular organisation of progenitor cells during vertebrate laterality organ formation.

Origin and shaping of the laterality organ in zebrafish.

Handedness of the vertebrate body plan critically depends on transient embryonic structures/organs that generate cilia-dependent leftward fluid flow within constrained extracellular environments. Although the function of ciliated organs in laterality determination has been extensively studied, how they are formed during embryogenesis is still poorly understood. Here we show that Kupffer's vesicle (KV), the zebrafish organ of laterality, arises from a surface epithelium previously thought to adopt exclusively extra-embryonic fates. Live multi-photon confocal imaging reveals that surface epithelial cells undergo Nodal/TGFbeta signalling-dependent ingression at the dorsal germ ring margin prior to gastrulation, to give rise to dorsal forerunner cells (DFCs), the precursors of KV. DFCs then migrate attached to the overlying surface epithelium and rearrange into rosette-like epithelial structures at the end of gastrulation. During early somitogenesis, these epithelial rosettes coalesce into a single rosette that differentiates into the KV with a ciliated lumen at its apical centre. Our results provide novel insights into the morphogenetic transformations that shape the laterality organ in zebrafish and suggest a conserved progenitor role of the surface epithelium during laterality organ formation in vertebrates.

RE-1 silencer of transcription/neural restrictive silencer factor modulates ectodermal patterning during Xenopus development.

RE-1 silencer of transcription/neural restrictive silencer factor (REST/NRSF), a transcriptional repressor, binds to the RE-1 element present in many vertebrate genes. In vitro studies indicate that REST/NRSF plays important roles in several stages of neural development. However, a full understanding of its physiological function requires in vivo approaches. We find that impairment of REST/NRSF function in Xenopus embryos leads to the perturbation of neural tube, cranial ganglia, and eye development. The origin of these defects is the abnormal patterning of the ectoderm during gastrulation. Interference of REST/NRSF function during the late blastula stage leads to an expansion of the neural plate, concomitant with a decrease of the expression of epidermal keratin and neural crest markers. Furthermore, neurogenesis proceeds abnormally, with loss of the expression of proneural, neurogenic, and neuronal genes. The interference of REST/NRSF mimics several features associated with a decreased bone morphogenetic protein (BMP) function and counteracts some effects of BMP4 misexpression. Our results indicate that REST/NRSF function is required in vivo for the acquisition of specific ectodermal cell fates.