Chun-Li Zhang, Yuhua Zou, Weimin He, Fred H. Gage, Ronald M. Evans.
Nature, Advance online publication | doi:10.1038/nature06562
Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress. Although newly generated neurons are able to migrate and preferentially incorporate into the neural network, how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions. The adult neural stem cell pool is composed of orphan nuclear receptor TLX-positive cells. Here, using genetic approaches in mice, we demonstrate that TLX (also called NR2E1) regulates adult neural stem cell proliferation in a cell-autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.# 学習や記憶には神経新生が関与しているらしい
John C. Crocker.
Nature 451, 528-529 (2008) | doi:10.1038/451528a
Dmytro Nykypanchuk, Mathew M. Maye, Daniel van der Lelie, Oleg Gang.
Nature 451, 549-552 (2008) | doi:10.1038/nature06560
Many nanometre-sized building blocks will readily assemble into macroscopic structures. If the process is accompanied by effective control over the interactions between the blocks and all entropic effects, then the resultant structures will be ordered with a precision hard to achieve with other fabrication methods. But it remains challenging to use self-assembly to design systems comprised of different types of building blocks―to realize novel magnetic, plasmonic and photonic metamaterials, for example. A conceptually simple idea for overcoming this problem is the use of 'encodable' interactions between building blocks; this can in principle be straightforwardly implemented using biomolecules. Strategies that use DNA programmability to control the placement of nanoparticles in one and two dimensions have indeed been demonstrated. However, our theoretical understanding of how to extend this approach to three dimensions is limited, and most experiments have yielded amorphous aggregates and only occasionally crystallites of close-packed micrometre-sized particles. Here, we report the formation of three-dimensional crystalline assemblies of gold nanoparticles mediated by interactions between complementary DNA molecules attached to the nanoparticles' surface. We find that the nanoparticle crystals form reversibly during heating and cooling cycles. Moreover, the body-centred-cubic lattice structure is temperature-tuneable and structurally open, with particles occupying only ~4% of the unit cell volume. We expect that our DNA-mediated crystallization approach, and the insight into DNA design requirements it has provided, will facilitate both the creation of new classes of ordered multicomponent metamaterials and the exploration of the phase behaviour of hybrid systems with addressable interactions.
Sung Yong Park, Abigail K. R. Lytton-Jean, Byeongdu Lee, Steven Weigand, George C. Schatz, Chad A. Mirkin.
Nature 451, 553-556 (2008) | doi:10.1038/nature06508
It was first shown more than ten years ago that DNA oligonucleotides can be attached to gold nanoparticles rationally to direct the formation of larger assemblies. Since then, oligonucleotide-functionalized nanoparticles have been developed into powerful diagnostic tools for nucleic acids and proteins, and into intracellular probes and gene regulators. In contrast, the conceptually simple yet powerful idea that functionalized nanoparticles might serve as basic building blocks that can be rationally assembled through programmable base-pairing interactions into highly ordered macroscopic materials remains poorly developed. So far, the approach has mainly resulted in polymerization, with modest control over the placement of, the periodicity in, and the distance between particles within the assembled material. That is, most of the materials obtained thus far are best classified as amorphous polymers, although a few examples of colloidal crystal formation exist. Here, we demonstrate that DNA can be used to control the crystallization of nanoparticle–oligonucleotide conjugates to the extent that different DNA sequences guide the assembly of the same type of inorganic nanoparticle into different crystalline states. We show that the choice of DNA sequences attached to the nanoparticle building blocks, the DNA linking molecules and the absence or presence of a non-bonding single-base flexor can be adjusted so that gold nanoparticles assemble into micrometre-sized face-centred-cubic or body-centred-cubic crystal structures. Our findings thus clearly demonstrate that synthetically programmable colloidal crystallization is possible, and that a single-component system can be directed to form different structures.# なんだか一気にDNAのナノ材料応用が進みそうな予感…
# 昔の実家の裏かと思った
# 確かにずいぶんと月とは違うな
Genta Ohno, Masatoshi Hagiwara, Hidehito Kuroyanagi.
Genes and Development, Advance Online Artivles | DOI: 10.1101/gad.1620608
Alternative splicing of pre-mRNAs greatly contributes to the spatiotemporal diversity of gene expression in metazoans. However, the molecular basis of developmental regulation and the precise sequence of alternative pre-mRNA processing in vivo are poorly understood. In the present study, we focus on the developmental switching of the mutually exclusive alternative splicing of the let-2 gene of Caenorhabditis elegans from the exon 9 form in embryos to the exon 10 form in adults. By visualizing the usage of the let-2 mutually exclusive exons through differential expression of green fluorescent protein (GFP) and red fluorescent protein (RFP), we isolated several switching-defective mutants and identified the alternative splicing defective-2 (asd-2) gene, encoding a novel member of the evolutionarily conserved STAR (signal transduction activators of RNA) family of RNA-binding proteins. Comparison of the amounts of partially spliced let-2 RNAs in synchronized wild-type and asd-2 mutant worms suggested that either of the introns downstream from the let-2 mutually exclusive exons is removed prior to the removal of the upstream ones, and that asd-2 promotes biased excision of intron 10 in the late larval stages. We propose that the developmental switching between alternative sequences of intron removal determines the ratio between the mature let-2 mRNA isoforms.#
# まさか「米国の専門誌」＝「Genes and Development」だとは思い及ばず…
# しかし、このラボ、このネタで論文出しまくってるな
Hidehito Kuroyanagi, Tetsuo Kobayashi, Shohei Mitani, Masatoshi Hagiwara.
Nature Methods 3, 909-915 (2006) | doi:10.1038/nmeth944
# ちなみに方法論は既にNature Methodsに出ています
# これもある意味、サイボーグ化
# ますます厳しくなるなぁ…けど、製造してなければ関係ないよね？
