Reconstitution of the central and peripheral nervous system during salamander tail regeneration.

We show that after tail amputation in Ambystoma mexicanum (Axolotl) the correct number and spacing of dorsal root ganglia are regenerated. By transplantation of spinal cord tissue and nonclonal neurospheres, we show that the central spinal cord represents a source of peripheral nervous system cells. Interestingly, melanophores migrate from preexisting precursors in the skin. Finally, we demonstrate that implantation of a clonally derived spinal cord neurosphere can result in reconstitution of all examined cell types in the regenerating central spinal cord, suggesting derivation of a cell with spinal cord stem cell properties.

CXCL5 into the upper airways of children with influenza A virus infection

BACKGROUND: Neutrophil infiltration is a major feature in the pathogenesis of influenza infection. The factors regulating the neutrophil influx are not fully understood. The chemokine CXCL5/ENA-78 is a potent neutrophil chemoattractant, that has been implicated in several inflammatory diseases. Our objectives was to study the release of CXCL5 in children with natural acquired influenza. METHODS: CXCL5 concentration was investigated by immunoenzyme assay in nasal aspirates of children (n = 18) in whom respiratory symptoms were precipitated predominantly by influenza A virus. RESULTS: There were increased CXCL5 levels in nasal aspirates when children were symptomatic as compared with samples from the same children when they had been asymptomatic for four weeks (medians 1850 pg/mL vs. 30 pg/mL, p < 0.005). We purified CXCL5 from these samples, and demonstrated biological neutrophil chemotactic activity. CONCLUSIONS: It is the first in vivo data that suggest an important role for CXCL5 in neutrophil influx in proven upper respiratory influenza infection. We suggest that CXCL5 might provide a target for therapeutic intervention in influenza induced respiratory diseases.

Germline transgenic methods for tracking cells and testing gene function during regeneration in the axolotl.

The salamander is the only tetrapod that regenerates complex body structures throughout life. Deciphering the underlying molecular processes of regeneration is fundamental for regenerative medicine and developmental biology, but the model organism had limited tools for molecular analysis. We describe a comprehensive set of germline transgenic strains in the laboratory-bred salamander Ambystoma mexicanum (axolotl) that open up the cellular and molecular genetic dissection of regeneration. We demonstrate tissue-dependent control of gene expression in nerve, Schwann cells, oligodendrocytes, muscle, epidermis, and cartilage. Furthermore, we demonstrate the use of tamoxifen-induced Cre/loxP-mediated recombination to indelibly mark different cell types. Finally, we inducibly overexpress the cell-cycle inhibitor p16 (INK4a) , which negatively regulates spinal cord regeneration. These tissue-specific germline axolotl lines and tightly inducible Cre drivers and LoxP reporter lines render this classical regeneration model molecularly accessible.

Reprogramming to pluripotency is an ancient trait of vertebrate Oct4 and Pou2 proteins.

The evolutionary origins of the gene network underlying cellular pluripotency, a central theme in developmental biology, have yet to be elucidated. In mammals, Oct4 is a factor crucial in the reprogramming of differentiated cells into induced pluripotent stem cells. The Oct4 and Pou2 genes evolved from a POU class V gene ancestor, but it is unknown whether pluripotency induced by Oct4 gene activity is a feature specific to mammals or was already present in ancestral vertebrates. Here we report that different vertebrate Pou2 and Oct4 homologues can induce pluripotency in mouse and human fibroblasts and that the inability of zebrafish Pou2 to establish pluripotency is not representative of all Pou2 genes, as medaka Pou2 and axolotl Pou2 are able to reprogram somatic cells into pluripotent cells. Therefore, our results indicate that induction of pluripotency is not a feature specific to mammals, but existed in the Oct4/Pou2 common ancestral vertebrate.