Neural induction: 10 years on since the ‘default model’
Introduction
It is now just over 10 years since data from the laboratories of Eddy De Robertis, Richard Harland, Ali Hemmati-Brivanlou and Doug Melton started to converge to a view that has become very influential: that in the early embryo, ectodermal cells have a ‘default’ neural fate, which they adopt if they receive no signals at all from neighbouring cells, and that during normal development, bone morphogenetic proteins (BMPs) inhibit this fate and specify epidermis on the ventral side of the embryo (reviewed in [1, 2, 3, 4]). While new data strongly suggest that this view may be a little too simplistic, the model continues to hang on.
Section snippets
Current status of the default model
Apparently supporting the model, two important papers from the De Robertis laboratory [5••, 6••] now show that when three different members of the BMP family (BMPs 2, 4 and 7) are inhibited by injection of morpholino antisense oligonucleotides at the one- or two-cell stage, the embryos have severe trunk defect but still display some dorsoventral polarity, including ventral tissues. However, when a more divergent member of the same family (anti-dorsalising morphogenetic factor, or ADMP) is
The elusive Notch
In the fly, the Notch receptor plays several key roles in specifying neuronal fates. It is therefore surprising that so little is known about its possible involvement in similar processes during the early stages of neural development in vertebrates, except perhaps in the choices between glial and neuronal fates and in neural crest identity, both of which occur at relatively later stages of development (see [21] for review). Two new studies begin to address this, both relating not only to the
Heads or tales?
From very early on, when Spemann and Mangold discovered the organiser and the phenomenon of neural induction in 1924 [25], neural induction has been intimately connected with head–tail patterning. The original study discovered that grafts of the organiser generate complete ectopic neural axes, extending from the brain to the tip of the tail. However, some investigators subsequently suggested that induction of the brain and of the trunk and tail are mediated by signals from different (‘head’,
The view from the nucleus
The neural induction field has traditionally concentrated on identifying signalling factors secreted by the organiser that are able to induce neural fates in other cells. While ultimately we need to understand such signals and when and how they act, a full understanding of the process will only be gleaned when we can also uncover the mechanisms responsible for directly activating neural-specific genes and repressing those required for specifying other cell identities. Studies such as these have
Conclusions
Classical experiments (starting from Spemann's original finding that a graft of the organiser induces a complete nervous system in ectopic regions of the host embryo) have often been interpreted as indicating that neural induction is a single event, occurring at a discrete time in development and involving not just the generation of a neural plate but of one that already displays a considerable amount of organisation. This view was even enhanced by the influential ‘default model’, whose most
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
Our research on these topics is currently funded by grants from the Medical Research Council, the National Institute of Mental Health (NIMH), the BBSRC and the European Union FP6 Network of Excellence ‘Cells into Organs’.
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