The Role of Sdf1/Cxcr4 Chemokine Signaling in Neurovascular Niche within the Adult Zebrafish Telencephalic Ventricular Zone

Hideto Nagai1,,Norihito Kishimoto1,2,Kohei Shimizu1,Kazuhide Asawakawa3, Akihiro Urasaki3, Holger Knaut4, Shigenori Nonaka5, Koichi Kawakami3, and Kazunobu Sawamoto1

1)Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences
2)Center for Integrated Medical Research, Keio University
3)Division of Molecular and Developmental Biology, National Institute of Genetics, and Department of Genetics, Graduate University for Advanced Studies (SOKENDAI)
4)NYU School of Medicine
5)Laboratory for Spatiotemporal Regulation, National Institute for Basic Biology

In the adult mammalian brain, newborn cells generated in the subventricular zone migrate towards the olfactory bulb (OB) through the rostral migratory stream (RMS), which are aligned with blood vessels. We have shown that adult zebrafish also possesses a comparable stem-cell niche in the telencephalic ventricular zone (TVZ), in which newly generated neuronal precursor cells (NPCs) migrate to the OB along blood vessels in the RMS. However, the molecular mechanisms underlying the formation of such structure and migration of NPCs in the migratory stream remain unclear. A stromal-derived factor (Sdf1) and CXC chemokine receptor 4 (Cxcr4) are candidate factors involved in the neurovascular niche, because they have been implicated in various types of CNS cell migration and homing to the blood vessels. Here, we investigated whether Sdf1/Cxcr4 signaling is involved in the adult zebrafish RMS. Initially, we found that Sdf1 and Cxcr4 are expressed in the blood vessels and NPCs in the TVZ, respectively. We found that perturbation of the Sdf1/Cxcr4 signaling resulted in the dispersion of NPCs from the migratory stream without affecting cell proliferation in the TVZ, eventually leading to the decreased number of mature neurons in the OB. Thus, our data suggest that the Sdf1/Cxcr4 chemokine signaling plays an important role in the neurovascular niche to maintain the RMS structure within the adult zebrafish TVZ for the migration of NPCs to the OB.