The function of many transcriptional regulators and long non-coding RNAs in neural development and the SVZ are poorly understood. KAP1 is an important transcriptional and epigenetic regulator that mediates silencing and heterochromatin formation. Here, we studied the function of KAP1 on postnatal and adult SVZ neurogenesis. We showed that knockdown of KAP1 in vivo disrupted normal SVZ neurogenesis and reduced the number of newborn neurons in the olfactory bulb. We also showed that KAP1 directly binds to Paupar, a vertebrate conserved lncRNA and forms a trimeric complex with Pax6. Similar to Kap1 we showed that Paupar is necessary for OB neurogenesis as Paupar knockdown decreased the number of newborn OB neurons. In both loss-of-function studies, newborn OB granule neurons appeared to have delayed morphological differentiation. Neither Kap1 or Paupar loss affected cell death. We have however generated data suggesting Paupar and Kap1 may regulate stem cell maintenance and self-renewal in vivo. Finally, we found that KAP1 and Paupar co-regulated genes important in self-renewal and differentiation. Together, these results provide understanding about the role of the transcription coregulator KAP1 and the lncRNA Paupar in SVZ neurogenesis.
I am a DPhil candidate at Francis Szele lab and obtained my master’s degree in molecular biology from the University of Southern California and my bachelor’s degree from King Saud University in Riyadh, Saudi Arabia.