Serotonin signaling contribution to an evolutionary success: the jaw joint of vertebrates

Serotonin (5-HT) is an ancient molecule that appeared very early during evolution, and it is present in different phyla. The 5-HT signaling system includes several G-coupled receptors and it is widely conserved in vertebrates. 5-HT is implicated in an astonishing number of biological processes and it has a key role as a morphogen in several complex networks during development before it can act as a neurotransmitter. Recent advances on how serotonin signaling can influence early development and its role in vertebrate morphogenesis come from mice and Xenopus. The emergence of jawed vertebrates (gnathostomes) from jawless vertebrates (agnathans) represents a major event in the evolution of vertebrates. The acquisition of a jaw is assumed to have occurred after the split between gnathostomes and jawless vertebrates. A crucial question concerns what changes were introduced in the developmental patterning programme to obtain a jaw joint that is one of the most innovative inventions in the history of vertebrates. Molecular and developmental studies performed in Xenopus revealed for the first time that serotonin, through the 5-HT2B receptor signaling, is both sufficient and necessary to modulate the shape and functionality of the jaw, including the jaw joint. Accordingly, serotonin can be added to the complex interactive network of extrinsic factors that regulates mandibular arch development, thus contributing to one of the major vertebrate successes in evolution

Platelet derived growth factor B gene expression in the Xenopus laevis developing central nervous system

Platelet-derived growth factor B (PDGF-B) belongs to the mitogen and growth factor family and like the other members it has many roles in cell differentiation, proliferation and migration during development, adult life and in pathological conditions. Among them it has been observed that aberrant PDGF signalling is frequently linked to glioma development and progression, and Pdgf-b over-expression in mouse neural progenitors leads to the formation of gliomas. Despite this evidence, the mechanisms underlying PDGF-B driven tumorigenesis and its role during brain development are not fully understood. In order to contribute to clarifying possible new roles of pdgf-b signalling, we present here the embryonic gene expression pattern of pdgf-b, so far unknown in early vertebrate development. By using Xenopus laevis as a model system we performed qRT-PCR and whole mount in situ hybridization. Pdgf-b mRNA is expressed in discrete regions of the developing central nervous system, in the cranial nerve placodes and in the notochord. We also compared the gene expression of pdgf-b with that of its receptor pdgfr-a suggesting so far unsuspected roles for this signalling pathway during the development of specific embryonic structures

The age-regulated zinc finger factor ZNF367 is a new modulator of neuroblast proliferation during embryonic neurogenesis.

Global population aging is one of the major social and economic challenges of contemporary society. During aging the progressive decline in physiological functions has serious consequences for all organs including brain. The age-related incidence of neurodegenerative diseases coincides with the sharp decline of the amount and functionality of adult neural stem cells. Recently, we identified a short list of brain age-regulated genes by means of next-generation sequencing. Among them znf367 codes for a transcription factor that represents a central node in gene co-regulation networks during aging, but whose function in the central nervous system (CNS), is completely unknown. As proof of concept, we analysed the role of znf367 during Xenopus laevis neurogenesis. By means of a gene loss of function approach limited to the CNS, we suggested that znf367 might act as a key controller of the neuroblast cell cycle, particularly in the progression of mitosis and spindle checkpoint. A candidate gene approach based on a weighted-gene co-expression network analysis, revealed fancd2 and ska3 as possible targets of znf367. The age-related decline of znf367 correlated well with its role during embryonic neurogenesis, opening new lines of investigation also in adult neurogenesis to improved maintenance and even repair of neuronal function

Immobilization of Monolayer Protected Lipophilic Gold Nanorods on a Glass Surface

We present a novel process of immobilization of gold nanorods (GNRs) on a glass surface. Wedemonstrate that by exploiting monolayer protection of the GNRs, their unusual opticalproperties can be completely preserved. UV–visible spectroscopy and atomic forcemicroscopy analysis are used to reveal the optical and morphological properties of monolayerprotected immobilized lipophilic GNRs, and molecular dynamics simulations are used toelucidate their surface molecule arrangements

Phantoms in medicine: the case of ophthalmology

Physical and in-silico phantoms have revealed extremely useful in the development of new surgical techniques and medical devices and for training purposes. The fabrication of eye phantoms requires knowledge of anatomy and physical principles beyond the eye physiology and medical instruments used in the clinical scenario. After a proper definition of phantoms and the discussion about their classification, the present work reviews the various phantoms developed in ophthalmology, illustrating the rationale of their design

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress

Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy

Converging Role for REEP1/SPG31 in Oxidative Stress

Mutations in the receptor expression-enhancing protein 1 gene (REEP1) are associated with hereditary spastic paraplegia type 31 (SPG31), a neurological disorder characterized by lengthdependent degeneration of upper motor neuron axons. Mitochondrial dysfunctions have been observed in patients harboring pathogenic variants in REEP1, suggesting a key role of bioenergetics in disease-related manifestations. Nevertheless, the regulation of mitochondrial function in SPG31 remains unclear. To elucidate the pathophysiology underlying REEP1 deficiency, we analyzed in vitro the impact of two different mutations on mitochondrial metabolism. Together with mitochondrial morphology abnormalities, loss-of-REEP1 expression highlighted a reduced ATP production with increased susceptibility to oxidative stress. Furthermore, to translate these findings from in vitro to preclinical models, we knocked down REEP1 in zebrafish. Zebrafish larvae showed a significant defect in motor axon outgrowth leading to motor impairment, mitochondrial dysfunction, and reactive oxygen species accumulation. Protective antioxidant agents such as resveratrol rescued free radical overproduction and ameliorated the SPG31 phenotype both in vitro and in vivo. Together, our findings offer new opportunities to counteract neurodegeneration in SPG31

RHAMM mRNA expression in proliferating and migrating cells of the developing central nervous system

Extracellular matrix components can influence cell behaviour by modulating a wide variety of events. In particular, the glycosaminoglycan hyaluronan is involved in many processes of the normal and pathological adult cells and it is essential for embryonic development. Two main HA receptors have been characterized in vertebrate developing embryos: CD44 and RHAMM. These receptors display completely different characteristics apart from their ability to bind hyaluronan. RHAMM is still the most mysterious hyaluronan receptor as it can act as cell surface receptor but it can also be localized in the cytoplasm or in the cell nucleus, displaying both hyaluronan dependent and independent functions. In particular, the role of RHAMM during embryogenesis is still largely unclear. We reported a detailed gene expression analysis of RHAMM during Xenopus laevis development comparing its mRNA distribution with that of the hyaluronan synthases and CD44 genes, in order to provide a first insight into the possible role of RHAMM during vertebrate embryogenesis. Our findings point out that RHAMM mRNA displays a specific distribution in proliferating regions of the developing neural tube and retina where synthesis of hyaluronan is not detected. On the contrary, RHAMM expression correlates with the expression of hyaluronan synthase-1 and hyaluronan-receptor CD44 gene expression in migrating cranial neural crest. These results suggest that during the central nervous system development RHAMM could be involved in cell proliferation and migration processes both in a hyaluronan independent and dependent manner