Highlights in DD

Abstract

, Dev Dyn 238:302-314) Multipotent neural stem/progenitor cells (NSPCs) are touted for their therapeutic potential in treating diseases of the nervous system. Here, Chiu and colleagues describe an improved method for isolating cell populations enriched for NSPCs. Previously, they showed that an isoform of fibroblast growth factor 1 (FGF1), FGF1B, is selectively expressed in NSPC habitats including the brain, brain stem, and spinal cord. Here, they tested whether an FGF1B-green fluorescent protein (F1B-GFP) reporter could be used to isolate NSPCs. The reporter was transfected into the human glioblastoma line, U-1240 MG, and cells were fluorescence-activated cell sorted for GFP and/or another NSPC marker, CD133. Cells positive for both markers had a significantly higher potential to make self-renewing neurospheres than cells positive for CD133 alone. Moreover, the double-positive cells could be induced to differentiate into neurons, glia, and oligodendrocytes. Transfecting and sorting for F1B-GFP was also successful for isolation of NSPCs from cultured T-antigen-positive brain tumors from mice transgenic for F1B driving expression of T-antigen (F1B-Tag), and from primary cultures of wild-type (wt) mouse brains. F1B-GFP(ϩ) neurospheres from E14.5 wt brains could more efficiently differentiate as neuronal, glia, and oligodendrocyte than F1B-GFP(Ϫ) cells, but at later stages (embryonic day 17.5, postnatal day 1) were only more efficient at generating neurons. Future work will determine whether isolating F1B-GFP(ϩ) embryonic stem (ES) or induced pluripotent stem (iPS) cells could be a useful way to harvest patient-specific NSPCs. Small siPs (Small interfering peptide (siP) for in vivo examination of the developing lung interactonome, by J. Craig Cohen, Erin Killeen, Avinash Chander, Ken-Ichi Takemaru, Janet E. Larson, Kate J. Treharne, Anil Mehta, Dev Dyn 238:386 -393) This work, investigating the interactome of the lung stretch response, gives a flavor of the potential of small interfering peptide (siP) technology. As the lung fills with fluid during development, changes in pressure launch a stretch induced differentiation pathway. The pathway involves an interaction between casein kinase 2 (CK2) and cystic fibrosis transmembrane conductance regulator (CFTR) that regulates phosphorylation and activation of NADPH oxidase (NOX), and changes in Wnt/␤-catenin signaling. Cohen et al. disrupted NOX activity in three ways, with siPs that (1) blocked binding between NOX's two subunits, (2) blocked NOX phosphorylation, and (3) interfered with the CK2/CFTR interaction. All three siPs caused both failure of NOX to associate with the plasma membrane, and alteration of Wnt/␤-catenin signaling. The former two also triggered a significant decrease of phosphorylated myosin light chain 20 (P-MLC 20 ), a marker for contracted smooth muscle, indicating activation of stretch-induced differentiation. The third caused decreased expression of MLC 20 , consistent with a previously reported finding that the CK2-CFTR interaction is required f...