Current projects in our laboratory address three fundamental aspects of the development, homeostasis, and pathology of the peripheral nervous system

Development and homeostasis of sensory epithelial architecture

Epithelia represent the most common tissue in metazoa. The epithelium of the skin, the lung or gut form the most effective barrier to environmental insult, such as infections or pollution. Using the zebrafish as experimental system, we are studying cell-fate aquisition and epithelial structure during sensory-organ growth, homeostasis and regeneration. We employ state-of-the-art in toto live imaging. Our recent work has resulted is the discovery of a novel tissue-level cellular behavior called "planar cell inversion". This remarkable tissue reorganization offers insights into the process that underlies epithelial mirror symmetry. In collaboration with physicists and mathematicians, we have begun to systematically quantify cellular behavior. We are also investigating how mechanical forces are transmitted between cell during tissue remodeling. This line of work should unveil the link between the genetic and mechanical bases of epithelial architecture. We also want to understand the influence of epithelial architecture on receptor-cell innervation.

Genetics and cell biology of sensorineural circuits

Peripheral sensory organs sense external signals to inform the central nervous system about the environment, which ultimately triggers appropriate behavioral reactions. We are systematically dissecting the assembly of neuronal first-order projections, whose study is important because is likely to form the basis of a neuroanatomical code that relays sensory information to the brain to create a central map of the sensory field. This projects combine the zebrafish and the fly Drosophila. We have recently discovered that the birth order of sensory neurons in the zebrafish mechanosensory latera line diversifies the lateral-line neural circuit, forming a convergent submap that triggers fast startle reactions, and a divergent submap that governs navigation accuracy. The assembly of neural submaps is a simple and elegant strategy to control appropriate behavioral reactions to the sensory context. Currently, we are researching on the combined activity of neurons, and whether neural submaps form the bases of sensory-range fractionation. We are also testing the hypothesis that the central encoding of the hydrodynamic field is based on the integration of the spatial distribution of sensory organs and the planar polarization of their constituent mechanosensory hair cells.

Integrative biology and medicine of peripheral neuropathies

Neuropathies of the peripheral nervous system that develop in patients suffering from diabetes, for example, are complex and difficult to study. The experimental advantages afforded by the zebrafish are allowing us to model diabetic neuropathies in the whole organism, and to combine genetic, molecular and bioinformatic approaches with optical methods to sense or reprogram the metabolic status of the relevant cells. This approach is aimed at testing specific hypotheses about fundamental aspects of disease development and progression, whose results are integrated to collaborative efforts with physicians to test their clinical relevance. We hope that this integrative biological and medical approach will provide a framework for the development of strategies of regenerative or palliative medicine aimed at ameliorating the negative effects of peripheral neuropathies in humans.