ID4 · Role of Id4 in the adult subventricular zone of normal and injured brain

Role of Id4 in the adult subventricular zone of normal and injured brain

The subventricular zone (SVZ) is one of the largest neurogenic niches in the adult brain of mammals. The SVZ harbours self-renewing neural stem cells (NSCs), which give rise to neural progenitor cells. These progenitor cells generate neuroblasts that migrate tangentially in chains to the olfactory bulb, where they differentiate into olfactory interneurons. Neurogenesis in the SVZ is tightly regulated by several intrinsic and extrinsic factors. Among extrinsic factors, the bone morphogenic protein (BMP) signalling pathway has been shown to positively regulate neurogenesis while inhibiting oligodendrocyte differentiation. However, the downstream transcriptional factors mediating the effects of BMPs on adult neurogenesis are not well characterized. Inhibitor of DNA binding 4 (Id4) is a helix-loop-helix (HLH) transcriptional regulator activated by BMP signalling. Id proteins participate in numerous cellular processes such as differentiation, proliferation and apoptosis, by dimerizing with bHLH transcription factors, preventing them from binding DNA. Id4 is strongly expressed in the developing central nervous system and regulates neural progenitor proliferation and differentiation. However, Id4 function in adult neurogenesis is unknown. Moreover, SVZ activation in response to stroke has been widely reported in several mouse models. Nevertheless, the molecular mechanisms driving this activation remain largely unknown. Understanding the mechanism triggering SVZ response to stroke can be essential to pave the way for the development of success regenerative strategies after this event. This is of vital importance for the society since stroke is the main cause of disability worldwide causing enormous personal and socioeconomics costs. Additionally, bringing an insight into stem cell regulation will path the way to better understand deregulation in a tumorigenic context. In the present work, we sought to understand the function of Id4 in adult neurogenesis in normal and ischemic conditions. The main objectives of this project where (i) to determine the function of Id4 in adult NSC by gain and loss of function experiments and (ii) to understand the role of Id4 in SVZ-induced response upon ischemic stroke.

Data: CORDIS, © European Union