Identification of molecular mechanisms underlying regeneration in vertebrate brains

In the adult zebrafish brain, life-long proliferation and neurogenesis occur in several ventricular stem cell zones. The widespread neurogenesis is associated with remarkable regenerative potential. In contrast to mammals, the regeneration in the zebrafish brain is characterized by the long-term survival of new neurons generated in response to injury. Therefore, the comparative studies of reaction to the injury in zebrafish and mammals are important approach to identify mechanisms limiting regenerative potential observed in mammals. To identify specific molecular programs and genes that are governing neurogenesis and tissue regeneration in the adult zebrafish telencephalon after injury, we performed a gene expression analysis after stab wound injury in the adult zebrafish brains. In order to compare different molecular responses to injury between the neurogenic ventricular zone (VZ), where the telencephalic progenitors are located, and the parenchyma (P), where new neurons gradually integrate, we collected samples by laser capture from both regions 2 and 7 days post lesion (dpl) and compared their gene expression pattern to the samples obtained from the intact brains. Amongst the pathways that are modulated after lesion, we characterized a new signaling pathway that is specifically regulated in the neurogenic VZ at 2dpl when the proliferative reaction to stab wound lesion is detected. The identified pathway and its role in regeneration both in the zebrafish brain and the mammalian brain will be discussed.