Multi Slim Como Tomar,

We show that Merkel cells are required for the molecular and functional maturation of the SAI neurons that innervate them. We conclude that BDNF produced by Merkel cells during a precise embryonic period guides SAI neuron development, providing the first direct evidence that the skin instructs sensory neuron molecular and functional maturation. Uranium, As and Ni were mainly present as low molecular mass LMM, less than 10 kDa species in all samples, indicating that these elemental species are mobile and potentially bioavailable. Furthermore, prototypical SAI electrophysiological signatures were absent from skin regions where Bdnf was deleted in embryonic Merkel cells.

The concentrations of U in water within the Kadji Sai area varied from 0. Uranium concentrations in the drinking water of Kadji Sai village were about the level recommended by the WHO for drinking water.

Uranium, As and Ni were mainly present as low molecular mass LMM, less than 10 kDa species in all samples, indicating that these elemental species are mobile and potentially bioavailable. The soils from the mining sites were enriched in U, As and trace metals.

Hot spots with elevated radioactivity levels were easily detected in Kadji Sai and radioactive particles were observed.

We studied this question in Merkel cell-neurite complexes, where slowly adapting type I SAI neurons innervate skin-derived Merkel cells.

Merkel cell ablation also decreased downstream TrkB signaling in DRGs, and altered the expression of genes associated with SAI development and function. Skin- and Merkel cell-specific deletion of Bdnf during embryogenesis, but not postnatal Bdnf deletion or Ntf3 deletion, reproduced these results.

Furthermore, prototypical SAI electrophysiological signatures were absent from skin regions where Bdnf was deleted in embryonic Merkel cells.

We conclude that BDNF produced by Merkel cells during a precise embryonic period guides SAI neuron development, providing the first direct evidence that the skin instructs sensory neuron molecular and functional maturation.