Autophagy is an evolutionarily conserved process that is essential for cellular homeostasis and organismal viability in eukaryotes. However, the extent of its functions in higher-order processes of organismal physiology and behavior is still unknown. Here, we report that autophagy is essential for the maintenance of balance in mice and that its deficiency leads to severe balance disorders. We generated mice deficient in autophagin-1 protease (Atg4b) and showed that they had substantial systemic reduction of autophagic activity. Autophagy reduction occurred through defective proteolytic processing of the autophagosome component LC3 and its paralogs, which compromised the rate of autophagosome maturation. Despite their viability, Atg4b-null mice showed unusual patterns of behavior that are common features of inner ear pathologies. Consistent with this, Atg4b-null mice showed defects in the development of otoconia, organic calcium carbonate crystals essential for sense of balance (equilibrioception). Furthermore, these abnormalities were exacerbated in Atg5 -/-mice, which completely lack the ability to perform autophagy, confirming that autophagic activity is necessary for otoconial biogenesis. Autophagy deficiency also led to impaired secretion and assembly of otoconial core proteins, thus hampering otoconial development. Taken together, these results describe an essential role for autophagy in inner ear development and equilibrioception and open new possibilities for understanding and treating human balance disorders, which are of growing relevance among the elderly population.

The neurotrophins are a family of polypeptide growth factors that are essential for the development and maintenance of the vertebrate nervous system. In recent years, data have emerged indicating that neurotrophins could have a broader role than their name might suggest. In particular, the putative role of NGF and its receptor TrkA in immune system homeostasis has become a much studied topic, whereas information on the other neurotrophins is scarce in this regard. This paper reviews what is known about the expression and possible functions of neurotrophins and their receptors in different immune tissues and cells, as well as recent data obtained from studies of transgenic mice in our laboratory. Results from studies to date support the idea that neurotrophins may regulate some immune functions. They also play an important role in the development of the thymus and in the survival of thymocytes.

The brain-derived neurotrophic factor (BDNF) gene is expressed in differentiating and post-mitotic neurons of the zebrafish embryo, where it has been implicated in Huntington's disease. Little is known, however, about the full complement of neuronal cell types that express BDNF in this important vertebrate model. Here, we further explored the transcriptional profiles during the first week of development using real-time quantitative polymerase chain reaction (RT-qPCR) and whole-mount in situ hybridization (WISH). RT-qPCR results revealed a high level of maternal contribution followed by a steady increase of zygotic transcription, consistent with the notion of a prominent role of BDNF in neuronal maturation and maintenance. Based on WISH, we demonstrate for the first time that BDNF expression in the developing brain of zebrafish is structure specific. Anatomical criteria and co-staining with genetic markers (shh, pax2a, emx1, krox20, lhx2b and lhx9) visualized major topological domains of BDNF-positive cells in the pallium, hypothalamus, posterior tuberculum and optic tectum. Moreover, the relative timing of BDNF transcription in the eye and tectum may illustrate a mechanism for coordinated development of the retinotectal system. Taken together, our results are compatible with a local delivery and early role of BDNF in the developing brain of zebrafish, adding basic knowledge to the study of neurotrophin functions in neural development and disease.

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The European sea bass, a member of the Moronidae family, is a food fish, considered one of the first models for the intensive breeding in salt water. It has nowadays an important and increasing presence in the international fishing markets. Sea basses are carnivorous, feeding on little fishes and invertebrates. Considering the important role of the tongue during the intraoral transport and the swallowing of food, scarce data are present in literature about its morphology. The aim of this study was to analyze the morphology of the tongue by means of scanning electron and light microscopy. Adult sea basses were obtained from the aquarium of the Sicilian Center of Experimental Ichthyiopathology of the University of Messina. The fishes were anaesthetized with MS 222 and the heads were then quickly removed and processed for the paraffin embedding and SEM processing. Three different tongue regions could be distinguished: an apex, a body, and a root. Scanning electron and light microscopy showed the presence of numerous canine-like teeth, surrounded by taste buds and numerous fungiform and conical papillae. The teeth were curved and their tips were posteriorly oriented. The results confirm, in teleosts too, the fundamental role of the tongue in the mechanics of food ingestion. Moreover, the presence of taste buds demonstrates the interaction of food processing and taste. These data could be a potential source to identify new and better methods of nutrition in the breeding of this fish.

The gilthead seabream is a food fish, one of the most frequently used in aquaculture. In the species of commercial interest, feeding in captivity is very important and this process is strictly related to the morphological characteristics of the oral cavity. The aim of this study is, using the standard procedures for light and scanning electron microscopy, to analyze the morphology of the tongue dorsal surface to show if relationships are present between the tongue morphology and the nutritional habits and choices of this farmed species. The main characteristic of the gilthead seabream oral cavity floor is the presence of an apical pouch, with, probably, a protective role mainly for the apical, free part of the tongue. Three zones, like in other teleosts, an apex, a body and a root, can be clearly distinguished. In the pouch foliate-like papillae were observed, while the whole tongue is characterized by the presence of two types of papillae, respectively with a fungiform and cylindroid aspect, both randomly distributed throughout the whole dorsal surface of the tongue. Scattered and numerous taste buds, with the typical pear-onion shape, together with small and numerous taste pores are also present, distributed throughout the tongue surface. Our results demonstrate that in the gilthead seabream important mechanic and sensory roles are carried out by specific anatomical structures. Our anatomical data could give, together with further biochemical and physiological data, an important support with the aim of improving the nutrition of aquaculture species.

The zebrafish is a common model for developmental studies including those regarding tooth, palate and tongue. Nevertheless, little information is available about the morphology of the oral cavity in this teleost, especially in adult animals. In this study we used light, scanning and transmission electron microscopy to describe in detail the morphology of the oral cavity of adult zebrafish. The oral cavity could be divided into three different zones: the outer containing the lips, the intermediate corresponding to the internal valves and the internal that corresponds to the tongue. In the upper and lower intermediate zones, there were semilunar shaped valves, more prominent in the upper part. The internal lower zones correspond to the palate and the tongue, which is an individualized structure filled with numerous transversal ridges. Both the intermediate and internal zones were covered by a stratified epithelium containing numerous mucous and rodlet cells. Present data provide the first description of the morphology and structure of the oral cavity in the adult zebrafish and might serve as a baseline for developmental studies of the oral cavity using this teleost as a model.