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Purpose: In recent years, the increase in the biopesticides synthesis for alternative agricultural uses has required their impacts study. Among these compounds, several of them are known to exert endocrinedisrupting (EDs) effects causing deregulation of physiological functions affecting cell signaling pathways involved in neural cell differentiation leading to developmental neurotoxicity. The objective of our study was to determine the impact of the biopesticide A6 structurally related to estrogenic EDs on zebrafish larvae, to define its toxicity, the mechanisms responsible, and to monitor the locomotors activity at nanomolar concentrations (0. 0.5, 5 and 50 nM). Materials and methods: Using imaging analysis tools, immunohistochemistry, quantitative PCR, and an automated behavior recording system (Zebrabox) we were able to assess these effects. Results: We have shown through its blue fluorescence properties that it accumulates in different parts of the body such as the intestine, adipose tissue, muscles, yolk sac and head. A6 also disrupted swimming behavior by affecting the expression of tyrosine hydroxylase (TH) in dopaminergic neurons. Conclusions: In conclusion, our study provided a mechanistic understanding of the A6 neurotoxic effect which could be the result of its binding to the estrogen receptor. [ABSTRACT FROM AUTHOR]

Summary Dorsal root ganglia (DRG) sensory neurons arise from heterogeneous precursors that differentiate in two neurogenic waves, respectively controlled by Neurog2 and Neurog1 . We show here that transgenic mice expressing a Zeb1/2 dominant-negative form (DBZEB) exhibit reduced numbers of nociceptors and altered pain sensitivity. This reflects an early impairment of Neurog1 -dependent neurogenesis due to the depletion of specific sensory precursor pools, which is slightly later partially compensated by the contribution of boundary cap cells (BCCs). Indeed, combined DBZEB expression and genetic BCCs ablation entirely deplete second wave precursors and, in turn, nociceptors, thus recapitulating the Neurog1 − / − neuronal phenotype. Altogether, our results uncover roles for Zeb family members in the developing DRGs; they show that the Neurog1 -dependent sensory neurogenesis can be functionally partitioned in two successive phases; and finally, they illustrate plasticity in the developing peripheral somatosensory system supported by the BCCs, thereby providing a rationale for sensory precursor diversity. [ABSTRACT FROM AUTHOR]