Transcriptional noise and cellular heterogeneity as sources of information in developing embryos

21 November 2008

Alfonso Martinez-Arias
Department of Genetics
University of Cambridge

Abstract

The development of an embryo requires the generation of many different cells and their coordinated organization into organs and structures which together configure an animal. The engine for these processes relies on an interplay between fixed lineages and conditional fates acting upon growing and diversifying cell ensembles. The notion of conditional fates is a very important one as its existence allows for pattern regulation: in a cell fate transition a cell spends sometime in an in-between state in which it has an equal probability to adopt the new fate or keep the original one. The choice—ie: the probability—of a transition, is regulated. Nowhere is this notion more spectacularly exemplified than in the development of early mammalian embryos when during the first five divisions cells do not commit to any particular fate and this results in a highly regulative mode of development; up to the four and sometimes even the eight cell stage, each cell can give rise to a whole mouse. Conversely mixing two or three embryos at these early stages results in only one mouse. Embryonic Stem (ES) cells are an extreme example of this behaviour. They are derived from the early embryo and appear to have captured the pluripotency characteristic of the cells of the early embryo.

I plan to consider an extrapolation of ideas about transcriptional noise in prokaryotic gene regulatory networks to multicellular developmental systems. Specifically I shall discuss the possibility that transcriptional noise affords a substrate for pattern formation and regulation and that for this reason multicellular organisms have evolved molecular networks dedicated to the promotion, maintenance and filtering of transcriptional noise.

References

  1. H H Chang, M Hemberg, M Barahona, D E Ingber, S Huang S, "Transcriptome-wide noise controls lineage choice in mammalian progenitor cells", Nature 453:544-547 2009. PubMed
  2. J E Dietrich, T Hiiragi, "Stochastic patterning in the mouse pre-implantation embryo", Development 134:4219-4231 2007. PubMed
  3. M Hoffmann, H H Chang, S Huang, D E Ingber, M Loeffler, J Galle, "Noise-driven stem cell and progenitor population dynamics", PLoS ONE 3:e2922 2008. PubMed
  4. P Hayward, T Kalmar, A Martinez Arias, "Wnt/Notch signalling and information processing during development", Development 135:411-424 2008. PubMed
  5. A Martinez Arias, P Hayward"Filtering transcriptional noise during development: concepts and mechanisms", Nat Rev Genet 7:34-44 2006. PubMed
  6. J Silva, A Smith, "Capturing pluripotency", Cell 132:532-536 2008. PubMed

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