PMID- 24139738
OWN - NLM
STAT- MEDLINE
DCOM- 20140708
LR  - 20211021
IS  - 1879-0445 (Electronic)
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 23
IP  - 21
DP  - 2013 Nov 4
TI  - Quantitative imaging of transcription in living Drosophila embryos links 
      polymerase activity to patterning.
PG  - 2140-5
LID - S0960-9822(13)01113-5 [pii]
LID - 10.1016/j.cub.2013.08.054 [doi]
AB  - Spatiotemporal patterns of gene expression are fundamental to every developmental 
      program. The resulting macroscopic domains have been mainly characterized by 
      their levels of gene products. However, the establishment of such patterns 
      results from differences in the dynamics of microscopic events in individual 
      cells such as transcription. It is unclear how these microscopic decisions lead 
      to macroscopic patterns, as measurements in fixed tissue cannot access the 
      underlying transcriptional dynamics. In vivo transcriptional dynamics have long 
      been approached in single-celled organisms, but never in a multicellular 
      developmental context. Here, we directly address how boundaries of gene 
      expression emerge in the Drosophila embryo by measuring the absolute number of 
      actively transcribing polymerases in real time in individual nuclei. 
      Specifically, we show that the formation of a boundary cannot be quantitatively 
      explained by the rate of mRNA production in each cell, but instead requires 
      amplification of the dynamic range of the expression boundary. This amplification 
      is accomplished by nuclei randomly adopting active or inactive states of 
      transcription, leading to a collective effect where the fraction of active nuclei 
      is modulated in space. Thus, developmental patterns are not just the consequence 
      of reproducible transcriptional dynamics in individual nuclei, but are the result 
      of averaging expression over space and time.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Garcia, Hernan G
AU  - Garcia HG
AD  - Joseph Henry Laboratories of Physics, Princeton University, Princeton, NJ 08544, 
      USA.
FAU - Tikhonov, Mikhail
AU  - Tikhonov M
FAU - Lin, Albert
AU  - Lin A
FAU - Gregor, Thomas
AU  - Gregor T
LA  - eng
GR  - P50 GM071508/GM/NIGMS NIH HHS/United States
GR  - R01 GM097275/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131017
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Drosophila Proteins)
RN  - EC 2.7.7.7 (DNA-Directed DNA Polymerase)
SB  - IM
CIN - Nat Rev Genet. 2013 Dec;14(12):823. PMID: 24166030
CIN - Curr Biol. 2013 Nov 4;23(21):R965-7. PMID: 24200326
MH  - Animals
MH  - Animals, Genetically Modified/embryology/genetics/metabolism
MH  - *Body Patterning
MH  - DNA-Directed DNA Polymerase/*genetics/metabolism
MH  - Drosophila Proteins/*genetics/metabolism
MH  - Drosophila melanogaster/embryology/*genetics/metabolism
MH  - Embryo, Nonmammalian/embryology/metabolism
MH  - *Gene Expression Regulation, Developmental
MH  - In Situ Hybridization, Fluorescence
MH  - Microscopy, Confocal
PMC - PMC3828032
MID - NIHMS523625
EDAT- 2013/10/22 06:00
MHDA- 2014/07/09 06:00
PMCR- 2014/11/04
CRDT- 2013/10/22 06:00
PHST- 2013/07/26 00:00 [received]
PHST- 2013/08/23 00:00 [revised]
PHST- 2013/08/28 00:00 [accepted]
PHST- 2013/10/22 06:00 [entrez]
PHST- 2013/10/22 06:00 [pubmed]
PHST- 2014/07/09 06:00 [medline]
PHST- 2014/11/04 00:00 [pmc-release]
AID - S0960-9822(13)01113-5 [pii]
AID - 10.1016/j.cub.2013.08.054 [doi]
PST - ppublish
SO  - Curr Biol. 2013 Nov 4;23(21):2140-5. doi: 10.1016/j.cub.2013.08.054. Epub 2013 
      Oct 17.