Highlights in DD


  • Julie Kiefer

“Highlights” is a new feature that calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section will spotlight significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms.

Smart choice (Brain-specific 1B promoter of FGF1 gene facilitates the isolation of neural stem/progenitor cells with self-renewal and multipotent capacities, by Yi-Chao Hsu, Don-Ching Lee, Su-Liang Chen, Wei-Chih Liao, Jia-Wei Lin, Wen-Ta Chiu, Ing-Ming Chiu, Dev Dyn238:302–314) 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(+) neurospheres from E14.5 wt brains could more efficiently differentiate as neuronal, glia, and oligodendrocyte than F1B-GFP(−) 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(+) 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 Dyn238:386–393) 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/β-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/β-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 for MLC 20 production. These data show that siPs are an effective means of understanding tissue- and stage-specific in vivo protein interactions, making siPs a technology that's easy to swallow.

Exquisite timing (The Caenorhabditis elegans heterochronic gene lin-14 coordinates temporal progression and maturation in the egg-laying system, by Ryan W. Johnson, Leah Y. Liu, Wendy Hanna-Rose, Helen M. Chamberlin, Dev Dyn238:394–404) Developmental timing is regulated by either sequential or modular mechanisms. In modular timing, independent events occur in a certain order (Mom receives a gift on her birthday and at Christmas). In sequential timing, each step is dependent on the one previous (buy a gift, wrap it, Mom opens it). In Caenorhabditis elegans, the modular heterochronic gene lin-14 ensures that certain developmental events occur appropriately at the L1 larval stage. Here, identification of a new allele, lin-14(sa485), reveal defects not previously seen in other lin-14 alleles, suggesting new functions for the gene. First, vulva inversion, an early step in vulva development, occurs precociously relative to gonad development. Second, delayed expression of a ventral uterine, uv1 cell-specific transgene shows retarded specification of these cells. Third, the mature vulva everts late. Although the latter two processes are both delayed, they are not linked. This conclusion is supported by the observation that animals engineered to lack uv1 cells do not exhibit vulva eversion delay. However, the delayed processes may be parallel, downstream consequences of an unidentified primary abnormality because animals that exhibit one defect also exhibit the other. These results show that lin-14 can control developmental timing of increments less than a full larval stage, supporting the idea that the gene can function as a sequential regulator. Thus, both modes of developmental timing are dependent upon at least one common regulator (the gift giver).