Embryological and genetic evidence indicates that the vertebrate head is induced by a different set of signals from those that organize trunk-tail development. The gene cerberus encodes a secreted protein that is expressed in anterior endoderm and has the unique property of inducing ectopic heads in the absence of trunk structures. Here we show that the cerberus protein functions as a multivalent growth-factor antagonist in the extracellular space: it binds to Nodal, BMP and Wnt proteins via independent sites. The expression of cerberus during gastrulation is activated by earlier nodal-related signals in endoderm and by Spemann-organizer factors that repress signalling by BMP and Wnt. In order for the head territory to form, we propose that signals involved in trunk development, such as those involving BMP, Wnt and Nodal proteins, must be inhibited in rostral regions.

The competence of a cell to respond to the signalling molecule retinoic acid (RA) is thought to depend largely on its repertoire of cognate zinc finger nuclear receptors. XCYP26 is an RA hydroxylase that is expressed differentially during early Xenopus development. In Xenopus embryos, XCYP26 can rescue developmental defects induced by application of exogenous RA, suggesting that the enzymatic modifications introduced inhibit RA signalling activities in vivo. Alterations in the expression pattern of a number of different molecular markers for neural development induced upon ectopic expression of XCYP26 reflect a primary function of RA signalling in hindbrain development. Progressive inactivation of RA signalling results in a stepwise anteriorization of the molecular identity of individual rhombomeres. The expression pattern of XCYP26 during gastrulation appears to define areas within the prospective neural plate that develop in response to different concentrations of RA. Taken together, these observations appear to reflect an important regulatory function of XCYP26 for RA signalling; XCYP26‐mediated modification of RA modulates its signalling activity and helps to establish boundaries of differentially responsive and non‐responsive territories.

In a search for novel developmental genes expressed in a spatially restricted pattern in dorsal ectoderm of Xenopus we have identified XAG-2, a cement gland-specific gene with a putative role in ectodermal patterning. XAG-2 encodes a secreted protein, which is expressed in the anterior region of dorsal ectoderm from late gastrula stages onwards. Activation of XAG-2 transcription is observed in response to organizer-secreted molecules including the noggin, chordin, follistatin and cerberus gene products. Overexpression of XAG-2 but not of the related cement gland marker XAG-1 induces both cement gland differentiation and expression of anterior neural marker genes in the absence of mesoderm formation. Further, we show that XAG-2 signaling depends on an intact fibroblast growth factor (FGF) signal transduction pathway and that XAG-2-induced anterior neural fate of ectodermal cells can be transformed to a more posterior character by retinoic acid. Based on these findings we propose a role for XAG-2 in the specification of dorsoanterior ectodermal fate, i.e. in the formation of cement gland and induction of forebrain fate of Xenopus.

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Development of the nervous system in the amphibian embryo is initiated during gastrulation by an inductive interaction between chordamesoderm and dorsal ectoderm. The induced ectoderm forms the neural plate while uninduced ectoderm generates epidermis. We screened for genes activated during gastrulation and expressed specifically in the nervous system of Xenopus laevis in the expectation that clones representing such genes will constitute useful markers for the study of early neurogenesis. Probes were prepared from adult brain RNA by subtraction with RNA from ovary and from different combifnations of adult kidney, muscle, and skin; cDNA libraries prepared from early to late neurula embryo RNA were screened with these probes. Six clones were chosen for further study. Three of these clones are not represented in the maternal RNA population but are activated at the late gastrula stage; the other three increase from a maternal base. Expression of five of the genes is restricted to the neural plate during embryogenesis, and all six are restricted to the central nervous system in premetamorphic tadpoles and adults. One of the clones encodes an apparently neurospecific isoform of f8-tubulin; the identity of the other clones is unknown. Expression of all six genes is suppressed in axis-deficient embryos that lack dorsal structures including the brain.Neural induction triggers the development of the nervous system, one of the first stages of tissue differentiation in the vertebrate embryo. The nature of the neural induction signal has been a challenging problem since the time ofthe Spemann and Mangold experiment (1) in which the phenomenon of induction was discovered. These authors transplanted the dorsal blastopore lip from one embryo into the ventral region of another and showed that this transplant was able to induce a second body axis including a second nervous system. In

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We describe a novel basic leucine zipper transcription factor, XXBP-1, which interacts with BMP-4 in a positive feedback loop. It is a maternal factor and is zygotically expressed in the dorsal blastopore lip and ventral ectoderm with the exception of the prospective neural plate during gastrulation. Overexpression of XXBP-1 leads to ventralization of early embryos as described for BMP-4, and inhibits neuralization of dissociated ectoderm. Consistent with mediating BMP signaling, we show that the ectopic expression of XXBP-1 recovers the expression of epidermal keratin and reverses the dorsalization imposed by truncated BMP receptor type I, indicating that it may act downstream of the BMP receptor. Its effects can be partially mimicked by a fusion construct containing the VP16 activator domain and the XXBP-1 DNA-binding domain. In contrast, fusing the DNA-binding domain to the even-skipped repressor domain leads to upregulation of the neural markers NCAM and nrp-1 in animal cap assay. Taken together, the results suggest a role for XXBP-1 in the control of neural differentiation, possibly as an activator.

A function for FGF-type peptide growth factors has been implied for early mesodermal patterning events in Xenopus laevis. FGF signalling operates via the MAP kinase cascade that can directly activate the transcription of organizer-expressed genes, such as Xbra and Xegr-1. We have recently provided evidence for a critical role of Ets-type transcription factors in FGF mediated Xegr-1 transcription activation. Here, we report on the identification of the Xenopus Ets-type protein ER81 that is expressed in a pattern overlapping with the ones of Xegr-1 and Xbra during gastrulation. Microinjection in XER81 encoding mRNA into ventral blastomeres of Xenopus embryos results in the induction of ectopic, tail-like protrusions, whereas dorsal overexpression results in disturbed eye development. In the animal cap assay, ectopic expression of XER81 is found to interfere with activin mediated induction of Xegr-1 and gsc, but not with the Xbra response to activin.