Dissection of gene function at clonal level using mosaic analysis with double markers

doi:10.1007/s11515-013-1279-6

Front Biol

2013, Vol. 8

Issue (6) : 557-568 https://doi.org/10.1007/s11515-013-1279-6

REVIEW

Dissection of gene function at clonal level using mosaic analysis with double markers

Simon HIPPENMEYER(

)

IST Austria (Institute of Science and Technology Austria), Am Campus 1, A-3400 Klosterneuburg, Austria

Download: PDF(595 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

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.

Keywords MADM genetic mosaic clonal analysis lineage tracing neural development genomic imprinting

Corresponding Author(s): HIPPENMEYER Simon,Email:simon.hippenmeyer@ist.ac.at

Issue Date: 01 December 2013

Cite this article:

Simon HIPPENMEYER. Dissection of gene function at clonal level using mosaic analysis with double markers[J]. Front Biol, 2013, 8(6): 557-568.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-013-1279-6
https://academic.hep.com.cn/fib/EN/Y2013/V8/I6/557

Fig.1 The MADM principle. MADM utilizes Cre/LoxP-dependent interchromosomal recombination to generate distinctly labeled homozygous mutant cells in an otherwise heterozygous background in mice. For MADM, two reciprocal chimeric marker genes – GT and TG – are targeted separately to identical loci on homologous chromosomes. Following recombinase-mediated interchromosomal recombination, functional green and red fluorescent proteins are reconstituted. If recombination occurred at the G2 phase and the two recombinant chromosomes were segregated into different daughter cells (X-Segregation, G2-X events), each daughter cell would express a single fluorescent protein. When a mutation of interest is introduced distal to one MADM cassette, then one of the daughter cells would be homozygous mutant (here the green cell) for the gene of interest, whereas its sibling, labeled by a different color (red), would be homozygous wild-type. In addition to G2-X events, recombination in G2 followed by Z-Segregation (G2-Z events, right branch), G1, or postmitoticrecombinations (not shown) do not alter the heterozygote genotype, but can produce double-labeled (yellow) cells. Adapted with permission from ().

Fig.2 MADM-labeled Neurons in Different Brain Regions.
A-DOverview of MADM-labeled cells in cortex (A), olfactory bulb (B), cerebellum (C) and hippocampus (D).
E-H Examples of excitatory pyramidal cells in cortex (E; MADM/), inhibitory interneurons in cortex (F; MADM/), Purkinje and granule cells in cerebellum (G; MADM/) and CA1 pyramidal cells in hippocampus (H; MADM/). E and G are adapted and modified with permission after ().

Fig.3 Mosaic Generation of Chromosomal Disomy to Probe Genomic Imprinting.
AG2-X MADM events result in near complete uniparental chromosomal disomy labeled in green (GFP) and red (tdT) fluorescent colors, respectively. The GT MADM cassette is inherited from the mother (♀) and the TG MADM cassette from the father (♂), as shown in this schematic, red cells harbor unimaternal chromosomal disomy (♀♀) and green cells unipaternal chromosomal disomy (♂♂). Consequently, maternally expressed genes (Mat, pink) are expressed at twice the normal dose and paternally expressed genes (Pat, blue) are not expressed in red cells with unimaternaldisomy. In contrast, paternally expressed genes are expressed at twice the normal dose and maternally expressed genes are not expressed in green, unipaternaldisomy cells. Thus, genes subject to imprinting are differentially expressed depending on the uniparental chromosomal disomy. Biallelically expressed genes (Bi, black) are not affected.
B-DMADM labeling of Chr.7 UPDs in the liver (B), heart (C) and brain (hippocampus) (D) at P21. The allele was introduced from the mother (pink), and theallele from the father (blue), consequently, the ♂♂ cells are green and ♀♀cells are red. Note the increased number of green ♂♂ cells in the liver (B) but equal number of green ♂♂ and red ♀♀ cells in heart (C) and brain (D). DAPI staining (blue) outline the general organization of the hippocampus. Adapted with permission from ().

1	Armakolas A, Klar A J (2006). Cell type regulates selective segregation of mouse chromosome 7 DNA strands in mitosis. Science , 311(5764): 1146-1149 doi: 10.1126/science.1120519 pmid:16497932
2	Ayala R, Shu T, Tsai L H (2007). Trekking across the brain: the journey of neuronal migration. Cell , 128(1): 29-43 doi: 10.1016/j.cell.2006.12.021 pmid:17218253
3	Badea T C, Wang Y, Nathans J (2003). A noninvasive genetic/pharmacologic strategy for visualizing cell morphology and clonal relationships in the mouse. J Neurosci , 23(6): 2314-2322
4	Barlow D P (2011). Genomic imprinting: a mammalian epigenetic discovery model. Annu Rev Genet , 45(1): 379-403 doi: 10.1146/annurev-genet-110410-132459 pmid:21942369
5	Bartolomei M S, Ferguson-Smith A C (2011). Mammalian genomic imprinting. Cold Spring Harb Perspect Biol , 3(7): 3 doi: 10.1101/cshperspect.a002592 pmid:21576252
6	Bi W, Yan J, Stankiewicz P, Park S S, Walz K, Boerkoel C F, Potocki L, Shaffer L G, Devriendt K, Nowaczyk M J, Inoue K, Lupski J R (2002). Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse. Genome Res , 12(5): 713-728 doi: 10.1101/gr.73702 pmid:11997338
7	Blair S S (2003). Genetic mosaic techniques for studying Drosophila development. Development , 130(21): 5065-5072 doi: 10.1242/dev.00774 pmid:12975340
8	Bonaguidi M A, Wheeler M A, Shapiro J S, Stadel R P, Sun G J, Ming G L, Song H (2011). In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell , 145(7): 1142-1155 doi: 10.1016/j.cell.2011.05.024 pmid:21664664
9	Branda C S, Dymecki S M (2004). Talking about a revolution: The impact of site-specific recombinases on genetic analyses in mice. Dev Cell , 6(1): 7-28 doi: 10.1016/S1534-5807(03)00399-X pmid:14723844
10	Brennand K, Huangfu D, Melton D (2007). All beta cells contribute equally to islet growth and maintenance. PLoS Biol , 5(7): e163 doi: 10.1371/journal.pbio.0050163 pmid:17535113
11	Buckingham M E, Meilhac S M (2011). Tracing cells for tracking cell lineage and clonal behavior. Dev Cell , 21(3): 394-409 doi: 10.1016/j.devcel.2011.07.019 pmid:21920310
12	Cajal S R y (1911). Histology of the Nervous System of Man and Vertebrates. Oxford University Press, Inc, Oxford 1995 Translation
13	Cepko C, Ryder E F, Austin C P, Walsh C, Fekete D M (1995). Lineage analysis using retrovirus vectors. Methods Enzymol , 254: 387-419 doi: 10.1016/0076-6879(95)54027-X pmid:8531701
14	Chow B Y, Han X, Boyden E S (2012). Genetically encoded molecular tools for light-driven silencing of targeted neurons. Prog Brain Res , 196: 49-61 doi: 10.1016/B978-0-444-59426-6.00003-3 pmid:22341320
15	Cowan W M (1998). The emergence of modern neuroanatomy and developmental neurobiology. Neuron , 20(3): 413-426 doi: 10.1016/S0896-6273(00)80985-X pmid:9539119
16	De Paola V, Arber S, Caroni P (2003). AMPA receptors regulate dynamic equilibrium of presynaptic terminals in mature hippocampal networks. Nat Neurosci , 6(5): 491-500 pmid:12692557
17	Desgraz R, Herrera P L (2009). Pancreatic neurogenin 3-expressing cells are unipotent islet precursors. Development , 136(21): 3567-3574 doi: 10.1242/dev.039214 pmid:19793886
18	Dessaud E, Yang L L, Hill K, Cox B, Ulloa F, Ribeiro A, Mynett A, Novitch B G, Briscoe J (2007). Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism. Nature , 450(7170): 717-720 doi: 10.1038/nature06347 pmid:18046410
19	Dymecki S M, Kim J C (2007). Molecular neuroanatomy’s “Three Gs”: a primer. Neuron , 54(1): 17-34 doi: 10.1016/j.neuron.2007.03.009 pmid:17408575
20	Espinosa J S, Luo L (2008). Timing neurogenesis and differentiation: insights from quantitative clonal analyses of cerebellar granule cells. J Neurosci , 28: 2301-2312
21	Espinosa J S, Wheeler D G, Tsien R W, Luo L (2009). Uncoupling dendrite growth and patterning: single-cell knockout analysis of NMDA receptor 2B. Neuron , 62(2): 205-217 doi: 10.1016/j.neuron.2009.03.006 pmid:19409266
22	Feil R, Brocard J, Mascrez B, LeMeur M, Metzger D, Chambon P (1996). Ligand-activated site-specific recombination in mice. Proc Natl Acad Sci USA , 93(20): 10887-10890 doi: 10.1073/pnas.93.20.10887 pmid:8855277
23	Feinberg A P (2007). Phenotypic plasticity and the epigenetics of human disease. Nature , 447(7143): 433-440 doi: 10.1038/nature05919 pmid:17522677
24	Feng G, Mellor R H, Bernstein M, Keller-Peck C, Nguyen Q T, Wallace M, Nerbonne J M, Lichtman J W, Sanes J R (2000). Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron , 28(1): 41-51 doi: 10.1016/S0896-6273(00)00084-2 pmid:11086982
25	Foo L C, Allen N J, Bushong E A, Ventura P B, Chung W S, Zhou L, Cahoy J D, Daneman R, Zong H, Ellisman M H, Barres B A (2011). Development of a method for the purification and culture of rodent astrocytes. Neuron , 71(5): 799-811 doi: 10.1016/j.neuron.2011.07.022 pmid:21903074
26	Franco S J, Müller U (2013). Shaping our minds: stem and progenitor cell diversity in the mammalian neocortex. Neuron , 77(1): 19-34 doi: 10.1016/j.neuron.2012.12.022 pmid:23312513
27	Gao P, Sultan K T, Zhang X J, Shi S H (2013). Lineage-dependent circuit assembly in the neocortex. Development , 140(13): 2645-2655 doi: 10.1242/dev.087668 pmid:23757410
28	Gorski J A, Talley T, Qiu M, Puelles L, Rubenstein J L, Jones K R (2002). Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J Neurosci , 22: 6309-6314
29	Hallonet M E, Le Douarin N M (1993). Tracing neuroepithelial cells of the mesencephalic and metencephalic alar plates during cerebellar ontogeny in quail-chick chimaeras. Eur J Neurosci , 5(9): 1145-1155 doi: 10.1111/j.1460-9568.1993.tb00969.x pmid:8281319
30	Hayashi S, McMahon A P (2002). Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse. Dev Biol , 244(2): 305-318 doi: 10.1006/dbio.2002.0597 pmid:11944939
31	Hegemann P, M?glich A (2011). Channelrhodopsin engineering and exploration of new optogenetic tools. Nat Methods , 8(1): 39-42 doi: 10.1038/nmeth.f.327 pmid:21191371
32	Hippenmeyer S, Johnson R L, Luo L (2013). Mosaic analysis with double markers reveals cell-type-specific paternal growth dominance. Cell Rep , 3: 960-967
33	Hippenmeyer S, Vrieseling E, Sigrist M, Portmann T, Laengle C, Ladle D R, Arber S (2005). A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol , 3(5): e159 doi: 10.1371/journal.pbio.0030159 pmid:15836427
34	Hippenmeyer S, Youn Y H, Moon H M, Miyamichi K, Zong H, Wynshaw-Boris A, Luo L (2010). Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration. Neuron , 68(4): 695-709 doi: 10.1016/j.neuron.2010.09.027 pmid:21092859
35	Imayoshi I, Ohtsuka T, Metzger D, Chambon P, Kageyama R (2006). Temporal regulation of Cre recombinase activity in neural stem cells. Genesis , 44(5): 233-238 doi: 10.1002/dvg.20212 pmid:16652364
36	Indra A K, Warot X, Brocard J, Bornert J M, Xiao J H, Chambon P, Metzger D (1999). Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases. Nucleic Acids Res , 27(22): 4324-4327 doi: 10.1093/nar/27.22.4324 pmid:10536138
37	Jefferis G S, Livet J (2012). Sparse and combinatorial neuron labelling. Curr Opin Neurobiol , 22(1): 101-110 doi: 10.1016/j.conb.2011.09.010 pmid:22030345
38	Lao Z, Raju G P, Bai C B, Joyner A L (2012). MASTR: a technique for mosaic mutant analysis with spatial and temporal control of recombination using conditional floxed alleles in mice. Cell Rep , 2: 386-396
39	Lee T, Luo L (1999). Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron , 22(3): 451-461 doi: 10.1016/S0896-6273(00)80701-1 pmid:10197526
40	Legué E, Joyner A L (2010). Genetic fate mapping using site-specific recombinases. Methods Enzymol , 477: 153-181 doi: 10.1016/S0076-6879(10)77010-5 pmid:20699142
41	Lehtinen M K, Walsh C A (2011). Neurogenesis at the brain-cerebrospinal fluid interface. Annu Rev Cell Dev Biol , 27(1): 653-679 doi: 10.1146/annurev-cellbio-092910-154026 pmid:21801012
42	Lewandoski M (2001). Conditional control of gene expression in the mouse. Nat Rev Genet , 2(10): 743-755 doi: 10.1038/35093537 pmid:11584291
43	Liang H, Xiao G, Yin H, Hippenmeyer S, Horowitz J M, Ghashghaei H T (2013). Neural development is dependent on the function of specificity protein 2 in cell cycle progression. Development , 140(3): 552-561 doi: 10.1242/dev.085621 pmid:23293287
44	Liu C, Sage J C, Miller M R, Verhaak R G, Hippenmeyer S, Vogel H, Foreman O, Bronson R T, Nishiyama A, Luo L, Zong H (2011). Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell , 146(2): 209-221 doi: 10.1016/j.cell.2011.06.014 pmid:21737130
45	Liu P, Jenkins N A, Copeland N G (2002). Efficient Cre-loxP-induced mitotic recombination in mouse embryonic stem cells. Nat Genet , 30(1): 66-72 doi: 10.1038/ng788 pmid:11740496
46	Lui J H, Hansen D V, Kriegstein A R (2011). Development and evolution of the human neocortex. Cell , 146(1): 18-36 doi: 10.1016/j.cell.2011.06.030 pmid:21729779
47	Luo L (2007). Fly MARCM and mouse MADM: genetic methods of labeling and manipulating single neurons. Brain Res Brain Res Rev , 55(2): 220-227 doi: 10.1016/j.brainresrev.2007.01.012 pmid:17408568
48	Mabb A M, Judson M C, Zylka M J, Philpot B D (2011). Angelman syndrome: insights into genomic imprinting and neurodevelopmental phenotypes. Trends Neurosci , 34(6): 293-303 doi: 10.1016/j.tins.2011.04.001 pmid:21592595
49	Madisen L, Zwingman T A, Sunkin S M, Oh S W, Zariwala H A, Gu H, Ng L L, Palmiter R D, Hawrylycz M J, Jones A R, Lein E S, Zeng H (2010). A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci , 13(1): 133-140 doi: 10.1038/nn.2467 pmid:20023653
50	Marín O, Valiente M, Ge X, Tsai L H (2010). Guiding neuronal cell migrations. Cold Spring Harb Perspect Biol , 2(2): a001834 doi: 10.1101/cshperspect.a001834 pmid:20182622
51	McConnell S K (1988). Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation. J Neurosci , 8: 945-974
52	Merkle F T, Mirzadeh Z, Alvarez-Buylla A (2007). Mosaic organization of neural stem cells in the adult brain. Science , 317(5836): 381-384 doi: 10.1126/science.1144914 pmid:17615304
53	Metzger D, Chambon P (2001). Site- and time-specific gene targeting in the mouse. Methods , 24(1): 71-80 doi: 10.1006/meth.2001.1159 pmid:11327805
54	Ming G L, Song H (2011). Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron , 70(4): 687-702 doi: 10.1016/j.neuron.2011.05.001 pmid:21609825
55	Miyoshi G, Hjerling-Leffler J, Karayannis T, Sousa V H, Butt S J, Battiste J, Johnson J E, Machold R P, Fishell G (2010). Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. J Neurosci , 30: 1582-1594
56	Morgan T H (1914). Mosaics and gynandromorphs in Drosophila. Proc Soc Exp Biol Med , 11(6): 171-172 doi: 10.3181/00379727-11-105
57	Muzumdar M D, Luo L, Zong H (2007). Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM). Proc Natl Acad Sci USA , 104(11): 4495-4500 doi: 10.1073/pnas.0606491104 pmid:17360552
58	Nelson S B, Sugino K, Hempel C M (2006). The problem of neuronal cell types: a physiological genomics approach. Trends Neurosci , 29(6): 339-345 doi: 10.1016/j.tins.2006.05.004 pmid:16714064
59	Nicholls R D, Knepper J L (2001). Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes. Annu Rev Genomics Hum Genet , 2(1): 153-175 doi: 10.1146/annurev.genom.2.1.153 pmid:11701647
60	Ninkovic J, Gotz M (2013). Fate specification in the adult brain-lessons for eliciting neurogenesis from glial cells. BioEssays , 35: 242-252
61	Novak A, Guo C, Yang W, Nagy A, Lobe C G (2000). Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision. Genesis , 28(3-4): 147-155 doi: 10.1002/1526-968X(200011/12)28:3/4<147::AID-GENE90>3.0.CO;2-G pmid:11105057
62	Petersen P H, Zou K, Hwang J K, Jan Y N, Zhong W (2002). Progenitor cell maintenance requires numb and numblike during mouse neurogenesis. Nature , 419(6910): 929-934 doi: 10.1038/nature01124 pmid:12410312
63	Reiner O, Carrozzo R, Shen Y, Wehnert M, Faustinella F, Dobyns W B, Caskey C T, Ledbetter D H (1993). Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats. Nature , 364(6439): 717-721 doi: 10.1038/364717a0 pmid:8355785
64	Ross M E, Walsh C A (2001). Human brain malformations and their lessons for neuronal migration. Annu Rev Neurosci , 24(1): 1041-1070 doi: 10.1146/annurev.neuro.24.1.1041 pmid:11520927
65	Sanes J R (1989). Analysing cell lineage with a recombinant retrovirus. Trends Neurosci , 12(1): 21-28 doi: 10.1016/0166-2236(89)90152-5 pmid:2471334
66	Schnütgen F, Doerflinger N, Calléja C, Wendling O, Chambon P, Ghyselinck N B (2003). A directional strategy for monitoring Cre-mediated recombination at the cellular level in the mouse. Nat Biotechnol , 21(5): 562-565 doi: 10.1038/nbt811 pmid:12665802
67	Shaner N C, Campbell R E, Steinbach P A, Giepmans B N, Palmer A E, Tsien R Y (2004). Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol , 22(12): 1567-1572 doi: 10.1038/nbt1037 pmid:15558047
68	Smith G B, Fitzpatrick D (2012). Specifying cortical circuits: a role for cell lineage. Neuron , 75(1): 4-5 doi: 10.1016/j.neuron.2012.06.032 pmid:22794254
69	Soriano P (1999). Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet , 21(1): 70-71 doi: 10.1038/5007 pmid:9916792
70	Stern C (1936). Somatic Crossing over and Segregation in Drosophila Melanogaster. Genetics , 21(6): 625-730 pmid:17246815
71	Tasic B, Miyamichi K, Hippenmeyer S, Dani V S, Zeng H, Joo W, Zong H, Chen-Tsai Y, Luo L (2012). Extensions of MADM (mosaic analysis with double markers) in mice. PLoS ONE , 7(3): e33332 doi: 10.1371/journal.pone.0033332 pmid:22479386
72	Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, Orban P C, Bock R, Klein R, Schütz G (1999). Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet , 23(1): 99-103 doi: 10.1038/12703 pmid:10471508
73	Tsai J W, Chen Y, Kriegstein A R, Vallee R B (2005). LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. J Cell Biol , 170(6): 935-945 doi: 10.1083/jcb.200505166 pmid:16144905
74	Walsh C, Cepko C L (1992). Widespread dispersion of neuronal clones across functional regions of the cerebral cortex. Science , 255(5043): 434-440 doi: 1734520" target="_blank">10.1126/science. pmid:1734520 pmid:1734520
75	Wingate R J, Hatten M E (1999). The role of the rhombic lip in avian cerebellum development. Development , 126(20): 4395-4404 pmid:10498676
76	Woodruff A, Xu Q, Anderson S A, Yuste R (2009). Depolarizing effect of neocortical chandelier neurons. Front Neural Circuits 3: 15.
77	Wynshaw-Boris A, Pramparo T, Youn Y H, Hirotsune S (2010). Lissencephaly: mechanistic insights from animal models and potential therapeutic strategies. Semin Cell Dev Biol , 21(8): 823-830 doi: 10.1016/j.semcdb.2010.07.008 pmid:20688183
78	Xu Q, Tam M, Anderson S A (2008). Fate mapping Nkx2.1-lineage cells in the mouse telencephalon. J Comp Neurol , 506(1): 16-29 doi: 10.1002/cne.21529 pmid:17990269
79	Xu T, Rubin G M (1993). Analysis of genetic mosaics in developing and adult Drosophila tissues. Development , 117(4): 1223-1237 pmid:8404527
80	Yang S B, Mclemore K D, Tasic B, Luo L, Jan Y N, Jan L Y (2012). Kv1.1-dependent control of hippocampal neuron number as revealed by mosaic analysis with double markers. J Physiol , 590(Pt 11): 2645-2658 pmid:22411008
81	Yingling J, Toyo-Oka K, Wynshaw-Boris A (2003). Miller-Dieker syndrome: analysis of a human contiguous gene syndrome in the mouse. Am J Hum Genet , 73(3): 475-488 doi: 10.1086/378096 pmid:12905154
82	Yingling J, Youn Y H, Darling D, Toyo-Oka K, Pramparo T, Hirotsune S, Wynshaw-Boris A (2008). Neuroepithelial stem cell proliferation requires LIS1 for precise spindle orientation and symmetric division. Cell , 132(3): 474-486 doi: 10.1016/j.cell.2008.01.026 pmid:18267077
83	Youn Y H, Pramparo T, Hirotsune S, Wynshaw-Boris A (2009). Distinct dose-dependent cortical neuronal migration and neurite extension defects in Lis1 and Ndel1 mutant mice. J Neurosci , 29: 15520-15530
84	Young P, Qiu L, Wang D, Zhao S, Gross J, Feng G (2008). Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice. Nat Neurosci , 11(6): 721-728 doi: 10.1038/nn.2118 pmid:18454144
85	Zhang F, Aravanis A M, Adamantidis A, de Lecea L, Deisseroth K (2007). Circuit-breakers: optical technologies for probing neural signals and systems. Nat Rev Neurosci , 8(8): 577-581 doi: 10.1038/nrn2192 pmid:17643087
86	Zhu X, Bergles D E, Nishiyama A (2008). NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development , 135(1): 145-157 doi: 10.1242/dev.004895 pmid:18045844
87	Zhuo L, Theis M, Alvarez-Maya I, Brenner M, Willecke K, Messing A (2001). hGFAP-cre transgenic mice for manipulation of glial and neuronal function in vivo. Genesis , 31(2): 85-94 doi: 10.1002/gene.10008 pmid:11668683
88	Zong H, Espinosa J S, Su H H, Muzumdar M D, Luo L (2005). Mosaic analysis with double markers in mice. Cell , 121(3): 479-492 doi: 10.1016/j.cell.2005.02.012 pmid:15882628

[1]	Fatih Semerci,Mirjana Maletic-Savatic. Transgenic mouse models for studying adult neurogenesis[J]. Front. Biol., 2016, 11(3): 151-167.
[2]	Daniel A. Berg,Ki-Jun Yoon,Brett Will,Alex Y. Xiao,Nam-Shik Kim,Kimberly M. Christian,Hongjun Song,Guo-li Ming. Tbr2-expressing intermediate progenitor cells in the adult mouse hippocampus are unipotent neuronal precursors with limited amplification capacity under homeostasis[J]. Front. Biol., 2015, 10(3): 262-271.
[3]	Gary R. HIME,Nicole SIDDALL,Katja HORVAY,Helen E. ABUD. Analyzing stem cell dynamics: use of cutting edge genetic approaches in model organisms[J]. Front. Biol., 2015, 10(1): 1-10.
[4]	Feng C. ZHOU. DNA methylation program during development[J]. Front Biol, 2012, 7(6): 485-494.

Viewed

Full text

Abstract

Cited

Shared

Discussed