title: Mcl-1 regulates the survival of adult neural precursor cells.
abstract: Since the discovery of neural precursor cells (NPCs) in the adult mammalian brain, there has been a lot of excitement surrounding the potential for regeneration in the adult brain. For instance, many studies have shown that a significant number of NPCs will migrate to a site of injury and differentiate into all of the neural lineages. However, one of the main challenges affecting endogenous neural regeneration is that many of the NPCs that migrate to the injury site ultimately undergo apoptosis. Therefore, we sought to determine whether myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic Bcl-2 protein, would promote the survival of adult NPCs by impeding apoptosis. To do this, we first confirmed that Mcl-1 is endogenously expressed within the adult NPC population using BrdU labeling assays. Next, we conditionally deleted Mcl-1 in adult NPCs using cre/lox technology and expressed Cre from the NPC-specific promoter Nestin. In vitro, cells that had Mcl-1 conditionally deleted had a 2-fold increase in apoptosis when compared to controls. In vivo, we used electroporation to conditionally delete Mcl-1 in adult NPCs and assessed apoptosis at 72h. after electroporation. As in our in vitro results, there was a 2-fold increase in apoptosis when Mcl-1 was conditionally deleted. Finally, we found that Mcl-1 over-expression reduced the endogenous rate of adult NPC apoptosis 2-fold in vitro. Collectively, these results demonstrate that Mcl-1 is crucial for the survival of adult NPCs and may be a promising target for future neural regeneration therapies.
authors.affiliation: Division of BioMedical Sciences, Memorial University of Newfoundland, St. John's, NL, Canada, A1B 3V6.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Malone
authors.forename: S M Mahmudul
authors.initials: SM
authors.lastname: Hasan
authors.forename: R Brian
authors.initials: RB
authors.lastname: Roome
authors.forename: Jieying
authors.initials: J
authors.lastname: Xiong
authors.forename: Michael
authors.initials: M
authors.lastname: Furlong
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Opferman
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Vanderluit
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014162:Transfection
chemical_list: C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2