The Origin Of Neonatal Neurons In The Striatum After Brain Injury And The Neurodevelopment Of The Septum

Neural stem cells from different regions within the subventricular zone (SVZ) are able to produce several different subtypes of interneurons in the olfactory bulb throughout life. Previous studies have shown that ischemic stroke induces the production of new interneurons in the damaged striatum from the SVZ. However, the origins and genetic profiles of these newborn neurons still remain largely unknown as SVZ neural stem cells are heterogeneous. In the present study, using a mouse model of perinatal hypoxic-ischemic brain injury combined with BrdU labeling methods, we found that, like in rat brains, virtually all newborn neuroblasts that migrate from the SVZ into the ischemic injured striatum exclusively express the transcription factor Sp8. Furthermore, although newborn neuroblasts are plentiful in the damaged striatum, only a few can differentiate into calretinin-expressing (CR+) interneurons that continuously express Sp8. Genetic fate mapping reveals that newly born CR+interneurons are generated from Emxl-expressing neural stem cells in the dorsal-lateral SVZ. These results suggest that the fate of Emxl-expressing lineage in the ischemic damaged striatum is restricted. However, when Sp8was conditionally inactivated in the Emxl-lineage cells, Pax6was ectopically expressed by a subpopulation of Emxl-derived, CR+cells in the normal and damaged striatum. Interestingly, these cells possessed large cell bodies and long processes. Our work identifies the origin of the newly born CR+interneurons in the damaged striatum after ischemic brain injury and bran neural stem cell can be modified in vivo by using transgenic methods. During the past few decades, tremendous progress has been achieved in the developmental research of CNS structures such as the cortex. The septum, with diverse projection neurons connecting a variety of brain structures, if not more, is at least as complicated as the cortex. However, the mechanism underlying its development remains poorly understood. Here, we defined this structure as a five-layer onion skin-like structure with different neuronal markers. However, the birth of septal neurons follows a sequence in a rough outside-in order. By examining three specific transgenic mouse lines and utilizing focal in utero electroporation, we provided evidence that not only the embryonic septal progenitor domains in itself but also three neighboring subpallial progenitor domains could contribute to the septal development. Thus, the neuronal diversity of the septum is achieved by sequential production of cell types in a defined spatial-temporal order through radial and tangential migrations.