Eric Wieschaus

Are there Common Genetic Principles that Govern Embryonic Development of all Organisms?


Abstract

The development of a fertilized egg into a complex individual with well-defined patterns of tissues and organs is an extraordinary process, one that that had fascinated biologists since Aristotle. In the past twenty years, many of the genes and developmental pathways that control cell behavior have been identified and their biochemical activities characterized. They fall into two general functional groups. A large fraction are transcription factors that bind directly to specific DNA sequences and control expression of adjacent genes. Specific combination of these transcription factors appear to define specific cell fates and after initial transient periods of expression, they are often maintained in cells throughout the course of their differentiation. The second group of gene activities that control cell behavior in the embryo appear to define signaling pathways that allow cells to communicate with each other and coordinated decisions across large regions of cells. The genes involved in these cell communication pathways encode proteins that are secreted into the extracellular environment, as well as cell surface receptors that allow cells to detect the signals secreted by their neighbors. Analysis of the genomic sequences, coupled with various experimental approaches, indicate that both the transcription factors and signaling pathways are remarkable conserved between organisms as diverse as flies, worm, frog, fish and humans. This conservation is consistent with the view that a common genetic strategy evolved to control embryonic development in the shared ancestor of all multicellular organisms and that this strategy has been generally maintained in the intervening 500 million years.

Despite the conservation of genes and signaling pathways, the initial stages of embryonic development are remarkably diverse. This diversity extends only to the size and morphology of embryos in individual species, but also in the mechanisms that that establish the initial assignment of cell fate. In some embryos, the cell fate choice of cells in a particular region of the embryo can be traced back to molecular distribution that exist in the cytoplasm of the egg cell prior to fertilization. Among the best-studied examples are the localized RNAs that are anchored at the future anterior and posterior pole of the Drosophila embryo. Translation of these RNAs establish gradients of protein within the egg that control cell fate. Because the RNAs themselves are make and localized during oogenesis in the mother, the pattern of embryonic development in Drosophila is prefigured and strictly correlated with patterning events occurring in the previous generation. Similar patterns of localized RNA are observed in the embryos of fish and frogs. In other organisms however, developmental patterns appear to arise in eggs with no obvious localized prepatterns. In such cases, complex spatial patterns arise (and appear to depend on a self organizing capacity of the embryo. The gene circuits for such self-organizing system are beginning to be identified. In the simplest models, they involve positive and negative feedbacks that amplify what are stochastic or high-variable spatial cues in the environment.

The mechanisms that establish patter in the early human embryo are not yet known but the general plasticity of mammalian embryo is likely that human embryos depend heavily signaling pathways that can generate de novo pattern. In my talk I will present experiment data from a large number of lab studying development in many different organism and will argue that the fundamental feature of the patterning process as well as specific gene activities are likely to be maintained in all organisms.


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