Trends in Genetics
ReviewHead in the WNT: the molecular nature of Spemann’s head organizer
Section snippets
Tissues involved in head induction
The organizer is not a homogeneous tissue but a dynamic structure; while cells involute during gastrulation they acquire different fates, inducing properties and gene expression profiles9, 10, 11, 12, 13. At the neurula stage at least four different regions derived from the gastrula organizer can be distinguished (Fig. 2; Table 1). From anterior to posterior these tissues are designated as anterior endoderm (also leading edge or yolky endoderm), prechordal plate (mesendodermal) as well as
Anti-BMPs as trunk inducers
In search of inducers that mediate inductions by the organizer, initially three secreted factors, Noggin, Chordin and Follistatin were identified in Xenopus. Our view of organizer function changed dramatically when it was realized that these inducers acted in a permissive fashion. They all antagonize signalling by bone morphogenetic proteins (BMP) and do so by sequestering BMP proteins into inactive complexes (reviewed in Ref. 9). When expressed at the ventral side of Xenopus embryos they
Two phases of class I WNT signalling in early Xenopus embryos
WNT glycoproteins are implicated in diverse processes during embryonic patterning in all metazoa tested32, 33. They bind to seven-transmembrane proteins of the frizzled type containing a conserved cysteine-rich extracellular domain (CRD)34. Two classes of WNT proteins can be distinguished, class I acting via β-catenin (e.g. Wnt-1 and Wnt-8) and class II transducing via phosphatidylinositol (e.g. Wnt-5a)35, although Xwnt-5a can also signal via the β-catenin route, if a matching frizzled receptor
Two-inhibitor model
Currently, the model most frequently applied for neural induction and regionalization is Nieuwkoop’s two-signal concept based on a neuralizing activator and a posteriorizing transformer. The two-inhibitor model49 (Fig. 1b) is a molecular interpretation thereof, extending the neural default concept according to which competent embryonal cells will differentiate to neural cells unless antagonized by BMP signalling8, 9, 63.
BMP and WNT signals from ectoderm and ventral mesoderm prevent
Posterior dominance revisited
Nieuwkoop’s experiments leading to the two-step model suggested that all neural tissue must pass through an anterior neural state, which is subsequently patterned by a transforming signal. This model was commonly interpreted as posterior differentiation being dominant over anterior (not to be confused with posterior prevalence in Hox gene function). Posterior dominance was indeed observed when both anterior and posterior organizer were used together as inducer in many experimental set-ups;
Conclusion
Head and trunk formation in the amphibian embryo are separate processes that require distinct inducing signals emanating from the Spemann organizer. Head induction is antagonized by growth factors of the TGF-β and WNT superfamilies. In this context, Nodals initially induce and later inhibit the head organizer, BMPs (1) ventralize dorsal mesoderm and (2) antagonize neuralization of ectoderm. WNTs (1) ventralize dorsal mesoderm, (2) posteriorize neuroectoderm, and (3) antagonize neuralization of
Acknowledgements
I thank T. Bouwmeester and M. Kessel as well as members of my lab for critically reading the manuscript. Scanning electron microscopy was skilfully carried out by N. Paweletz and A. Glinka.
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