@article{2855,
  abstract     = {Genomic imprinting leads to preferred expression of either the maternal or paternal alleles of a subset of genes. Imprinting is essential for mammalian development, and its deregulation causes many diseases. However, the functional relevance of imprinting at the cellular level is poorly understood for most imprinted genes. We used mosaic analysis with double markers (MADM) in mice to create uniparental disomies (UPDs) and to visualize imprinting effects with single-cell resolution. Although chromosome 12 UPD did not produce detectable phenotypes, chromosome 7 UPD caused highly significant paternal growth dominance in the liver and lung, but not in the brain or heart. A single gene on chromosome 7, encoding the secreted insulin-like growth factor 2 (IGF2), accounts for most of the paternal dominance effect. Mosaic analyses implied additional imprinted loci on chromosome 7 acting cell autonomously to transmit the IGF2 signal. Our study reveals chromosome- and cell-type specificity of genomic imprinting effects.},
  author       = {Hippenmeyer, Simon and Johnson, Randy and Luo, Liqun},
  journal      = {Cell Reports},
  number       = {3},
  pages        = {960 -- 967},
  publisher    = {Cell Press},
  title        = {{Mosaic analysis with double markers reveals cell type specific paternal growth dominance}},
  doi          = {10.1016/j.celrep.2013.02.002},
  volume       = {3},
  year         = {2013},
}

@article{2264,
  abstract     = {Faithful progression through the cell cycle is crucial to the maintenance and developmental potential of stem cells. Here, we demonstrate that neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs) employ a zinc-finger transcription factor specificity protein 2 (Sp2) as a cell cycle regulator in two temporally and spatially distinct progenitor domains. Differential conditional deletion of Sp2 in early embryonic cerebral cortical progenitors, and perinatal olfactory bulb progenitors disrupted transitions through G1, G2 and M phases, whereas DNA synthesis appeared intact. Cell-autonomous function of Sp2 was identified by deletion of Sp2 using mosaic analysis with double markers, which clearly established that conditional Sp2-null NSCs and NPCs are M phase arrested in vivo. Importantly, conditional deletion of Sp2 led to a decline in the generation of NPCs and neurons in the developing and postnatal brains. Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain.},
  author       = {Liang, Huixuan and Xiao, Guanxi and Yin, Haifeng and Hippenmeyer, Simon and Horowitz, Jonathan and Ghashghaei, Troy},
  journal      = {Development},
  number       = {3},
  pages        = {552 -- 561},
  publisher    = {Company of Biologists},
  title        = {{Neural development is dependent on the function of specificity protein 2 in cell cycle progression}},
  doi          = {10.1242/dev.085621},
  volume       = {140},
  year         = {2013},
}

@article{2303,
  abstract     = {MADM (Mosaic Analysis with Double Markers) technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cre recombinase/loxP-dependent interchromosomal mitotic recombination to reconstitute two split marker genes—green GFP and red tdTomato—and can label sparse clones of homozygous mutant cells in one color and wild-type cells in the other color in an otherwise unlabeled background. At present, major MADM applications include lineage tracing, single cell labeling, conditional knockouts in small populations of cells and induction of uniparental chromosome disomy to assess effects of genomic imprinting. MADM can be applied universally in the mouse with the sole limitation being the specificity of the promoter controlling Cre recombinase expression. Here I review recent developments and extensions of the MADM technique and give an overview of the major discoveries and progresses enabled by the implementation of the novel genetic MADM tools.},
  author       = {Hippenmeyer, Simon},
  journal      = {Frontiers in Biology},
  number       = {6},
  pages        = {557 -- 568},
  publisher    = {Springer},
  title        = {{Dissection of gene function at clonal level using mosaic analysis with double markers}},
  doi          = {10.1007/s11515-013-1279-6},
  volume       = {8},
  year         = {2013},
}

@article{2263,
  abstract     = {Nestin-cre transgenic mice have been widely used to direct recombination to neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs). Here we report that a readily utilized, and the only commercially available, Nestin-cre line is insufficient for directing recombination in early embryonic NSCs and NPCs. Analysis of recombination efficiency in multiple cre-dependent reporters and a genetic mosaic line revealed consistent temporal and spatial patterns of recombination in NSCs and NPCs. For comparison we utilized a knock-in Emx1cre line and found robust recombination in NSCs and NPCs in ventricular and subventricular zones of the cerebral cortices as early as embryonic day 12.5. In addition we found that the rate of Nestin-cre driven recombination only reaches sufficiently high levels in NSCs and NPCs during late embryonic and early postnatal periods. These findings are important when commercially available cre lines are considered for directing recombination to embryonic NSCs and NPCs.},
  author       = {Liang, Huixuan and Hippenmeyer, Simon and Ghashghaei, H.},
  journal      = {Biology open},
  number       = {12},
  pages        = {1200 -- 1203},
  publisher    = {The Company of Biologists},
  title        = {{A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors}},
  doi          = {10.1242/bio.20122287},
  volume       = {1},
  year         = {2012},
}