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

21 November 2008

Alfonso Martinez-Arias
Department of Genetics
University of Cambridge


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.


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