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Roof plate-dependent patterning of the vertebrate dorsal central nervous system.

In the vertebrate central nervous system (CNS), diverse cellular types are generated in response to inductive signals provided by specialized cellular groups that act as organizing centers. The roof plate is a critical dorsal signaling center that occupies the dorsal midline of the developing CNS along its entire anterior-posterior axis. During caudal neural tube development, the roof plate produces proteins of the Bmp and Wnt families controlling proliferation, specification, migration, and axon guidance of adjacent dorsal interneurons. Although primarily investigated in the developing spinal cord, a growing number of studies indicate that roof plate-derived signals are also critical for the patterning of dorsal structures in more rostral regions of CNS including the hindbrain, diencephalon and telencephalon. In this review, we discuss recent progress towards understanding the molecular and cellular mechanisms of roof plate-dependent patterning of the dorsal CNS.

Animals↗

A model for budding in hydra: pattern formation in concentric rings.

Current models of pattern formation in Hydra propose head-and foot-specific morphogens to control the development of the body ends and along the body length axis. In addition, these morphogens are proposed to control a cellular parameter (positional value, source density) which changes gradually along the axis. This gradient determines the tissue polarity and the regional capacity to form a head and a foot, respectively, in transplantation experiments. The current models are very successful in explaining regeneration and transplantation experiments. However, some results obtained render problems, in particular budding, the asexual way of reproduction is not understood. Here an alternative model is presented to overcome these problems. A primary system of interactions controls the positional values. At certain positional values secondary systems become active which initiate the local formation of e.g. mouth, tentacles, and basal disc. (i) A system of autocatalysis and lateral inhibition is suggested to exist as proposed by Gierer and Meinhardt (Kybernetik 12 (1972) 30). (ii) The activator is neither a head nor a foot activator but rather causes an increase of the positional value. (iii) On the other hand, a generation of the activator leads to its loss from cells and therewith to a (local) decrease of the positional value. (iv) An inhibitor is proposed to exist which antagonizes an increase of the positional value. External conditions like the gradient of positional values in the surroundings and interactions with other sites of morphogen production decide whether at a certain site of activator generation the positional value will increase (head formation), decrease (foot formation) or increase in the centre and decrease in the periphery thereby forming concentric rings (bud formation). Computer-simulation experiments show basic features of budding, regeneration and transplantation.

Animals↗

Segmentation of the paraxial mesoderm and vertebrate somitogenesis.

Somites are the most obviously segmented features of the vertebrate embryo. Although the way segmentation is achieved in the fly is now well described, little was known about the molecular mechanisms underlying vertebrate somitogenesis. Through the recent identification of genes important for vertebrate somitogenesis and the analysis of their function, several theoretical models accounting for somitogenesis such as the clock and wavefront model, which have been proposed over the past 20 years, are now starting to receive experimental support. A molecular clock linked to somitogenesis has been identified which might act as a periodicity generator in the presomitic cells. This temporal periodicity is then translated into a tightly controlled spatial periodicity which is revealed by the expression of several genes. Analysis of mouse mutants in the Notch-Delta pathway suggest that this signaling mechanism might play an important role at this level. The final step of the cascade is to translate these genetically specified segments into morphological units: the somites. Importantly, these studies have helped in dissociating the segmentation and the somitogenesis processes in vertebrates. In addition, although segmentation was classically thought to have arisen independently in protostomes and deuterostomes, recent evidence suggests that part of the segmentation machinery might actually have been conserved. The conservation of segmentation mechanisms reported in the fly such as the pair-rule pattern, however, remain a subject of controversy.

Animals↗

Negative regulation of dorsal patterning in early embryos by overexpression of XrelA, a Xenopus homologue of NF-kappa B.

Recent results by Richardson et al. (Mech. Dev., 52 (1995) 165-177) suggest that the Xenopus Rel gene XrelA may be involved in the formation of the head and tail of the early embryo. We present evidence to suggest that wild-type XrelA also has a role in dorsoventral development. XrelA overexpression in the dorsal side of embryos reduces dorsal development and attenuates in vitro dorsal morphogenetic movements. XrelA also strongly reduces axis duplication caused by overexpression of a dominant negative mutant of Xenopus glycogen synthase kinase-3 beta. Our results indicate that XrelA may have a role in dorsoventral patterning in early embryos.

Age Factors↗

Wing surface interactions in venation patterning in Drosophila.

The adult wing of Drosophila consists of two wing surfaces apposed by their basal membranes which first came into contact following disc eversion at metamorphosis. Veins appear in these surfaces in a dorsal-ventral symmetric pattern, but are 'corrugated' (vein cells are more compacted and more pigmented) in a dorsal-ventral asymmetric pattern. We prevented dorsal-ventral contact apposition during wing imaginal disc morphogenesis by implanting fragments of discs into metamorphosing hosts. In these implants, longitudinal veins differentiate but with wider corrugation and in both surfaces. These results and those of genetic mosaics of mutants removing veins or causing ectopic veins reveal mutual dorso-ventral induction/inhibition at work to modulate the final vein differentiation pattern and corrugation.

Animals↗

Analysis of Drosophila salivary gland, epidermis and CNS development suggests an additional function of brinker in anterior-posterior cell fate specification.

Salivary glands are simple structured organs which can serve as a model system in the study of organogenesis. Following a large EMS mutagenesis we have identified a number of genes required for normal salivary gland development. Mutations in the locus small salivary glands-1 (ssg-1) lead to a drastic reduction in the size of the salivary glands. The gene ssg-1 was cloned and subsequent sequence and genetic analysis showed identity to the recently published gene brinker. The salivary gland placode in brinker mutants appears reduced along both the anterior-posterior and dorso-ventral axis. Analysis of the brinker cuticle phenotype revealed a similar loss of anterior-posterior as well as lateral cell fates. The abdominal ventral denticle belts show a reduced number of setae in the first denticle row. Furthermore, we observed a preferential loss of lateral neuroblasts in the anterior parasegment. Together, these phenotypes suggest that brinker not only plays a role in dorso-ventral but also in anterior-posterior axis patterning.

Adhesins, Bacterial↗

Translational repression: a duet of Nanos and Pumilio.

Recent studies have shed new light on translational repression by Nanos and Pumilio proteins. The ancestral function of this repression mechanism appears to be in early germline development; later, species-specific applications in embryonic patterning and spermatogenesis-oogenesis switching evolved.

Animals↗

Vascular development: tracing signals along veins.

The plant hormone auxin has been implicated in vascular development, but the molecular details of patterned vascular differentiation have remained elusive. Research in the past year has identified new genes that control vascular patterning, and auxin transport and perception. New experimental strategies have been employed to study vascular development. Together, these findings have generated a conceptual framework and experimental tools for the exploration of vascular-tissue patterning at the molecular level.

Arabidopsis↗

The neural plate specifies somite size in the Xenopus laevis gastrula.

The organizer has traditionally been considered the major source of somite-inducing signals. We show here that signaling from the neural plate specifies somite tissue and regulates somite size in the Xenopus gastrula. Ectopic undifferentiated neural tissue induces massive somite expansion at the expense of intermediate and lateral plate mesoderm. Although the early expanded somite expresses muscle-specific markers, only a portion terminally differentiates, suggesting that myotome development requires additional signals. Explant assays demonstrate that neural tissue induces somite-specific marker expression even in the absence of the organizer. Finally, we demonstrate that neural tissue is required for proper somite development because elimination of neural precursors results in pronounced somite reduction. Thus, an important reciprocal interaction exists between somite and neural tissue that is mutually reinforcing and critical for normal embryonic patterning.

Animals↗

A new view of patterning domains in the vertebrate mesoderm.

The musculoskeletal system of vertebrates is derived from the embryonic mesoderm. Its structures are categorized as epaxial or hypaxial based on their adult position and innervation. The epaxial/hypaxial terminology is also used to describe regions of the embryonic somites based on fate mapping of somitic derivatives. However, the adult, functional distinctions are not fully consistent with the changing embryonic environments of mesodermal populations during morphogenesis, and the traditional terminology loses accuracy when used to describe certain mutant phenotypes. Here we describe a new terminology naming two mesodermal environments defined by the lineage of the included cells. We discuss how mutant phenotypes may be better explained by consideration of the embryonic context in which genes take their effect and argue that the recognition of these embryonic territories clarifies description and discussion of the morphogenesis and patterning of the musculoskeletal system.

Animals↗

A genome analysis of endoreplication in the Drosophila ovary.

Gene amplification is used by follicle cells to increase the copy number of Drosophila chorion genes, which encode structural components of the eggshell. A new study by Claycomb et al. in this issue of Developmental Cell raises the possibility that gene amplification might also be used for the developmental patterning of the egg chamber and oocyte.

Animals↗

Antero-posterior tissue polarity links mesoderm convergent extension to axial patterning.

Remodelling its shape, or morphogenesis, is a fundamental property of living tissue. It underlies much of embryonic development and numerous pathologies. Convergent extension (CE) of the axial mesoderm of vertebrates is an intensively studied model for morphogenetic processes that rely on cell rearrangement. It involves the intercalation of polarized cells perpendicular to the antero-posterior (AP) axis, which narrows and lengthens the tissue. Several genes have been identified that regulate cell behaviour underlying CE in zebrafish and Xenopus. Many of these are homologues of genes that control epithelial planar cell polarity in Drosophila. However, elongation of axial mesoderm must be also coordinated with the pattern of AP tissue specification to generate a normal larval morphology. At present, the long-range control that orients CE with respect to embryonic axes is not understood. Here we show that the chordamesoderm of Xenopus possesses an intrinsic AP polarity that is necessary for CE, functions in parallel to Wnt/planar cell polarity signalling, and determines the direction of tissue elongation. The mechanism that establishes AP polarity involves graded activin-like signalling and directly links mesoderm AP patterning to CE.

Activins↗

Transgenic Wnt/TCF pathway reporters: all you need is Lef?

The Wnt signaling pathway controls a large and diverse set of cell fate decisions in embryonic development, adult organ maintenance and disease. At the transcriptional level, Wnt/beta-catenin signaling is primarily mediated by the T-cell factor (TCF)/Lef-1 family of transcription factors, referred to here as TCFs. In order to track Wnt pathway activity during animal development, several laboratories have built transgenic reporter constructs containing multimerized TCF binding sites. Most of these reporters are active at multiple known sites of Wnt signaling, and several act as faithful reporters of pathway activity in specific contexts. However, multimerized TCF reporters should not be assumed to give a complete or definitive readout of Wnt signaling in vivo. Direct comparisons reveal discrepancies among reporters; in addition, there is good reason to expect that some important types of pathway activity, including target gene de-repression and TCF-independent Wnt or beta-catenin signaling, will not be accurately reported by such constructs. This review will discuss various transgenic Wnt/beta-catenin/TCF reporters, address the fidelity and completeness of their Wnt responsiveness, and contrast their in vivo transcriptional responses with those of natural Wnt target genes. Finally, three caveats to the interpretation of multimerized TCF reporter expression patterns will be proposed.

Animals↗

Co-option of an oral-aboral patterning mechanism to control left-right differentiation: the direct-developing sea urchin Heliocidaris erythrogramma is sinistralized, not ventralized, by NiCl2.

Larval dorsoventral (DV) and left-right (LR) axial patterning unfold progressively in sea urchin development, leading to commitment of the major embryonic regions by the gastrula stage. The direct-developing sea urchin Heliocidaris erythrogramma has lost oral-aboral differentiation along the DV axis but has accelerated vestibular ectoderm development on the left side. NiCl(2) radializes indirect-developing sea urchins by shifting cells toward a ventral fate (oral ectoderm). We treated embryos of H. erythrogramma and the indirect-developing H. tuberculata with NiCl(2). H. tuberculata was ventralized exactly like other indirect developers, establishing that basic patterning mechanisms are conserved in this genus. H. erythrogramma was also radialized; timing, dosage response, and some morphological features were similar to those in other sea urchins. Ectodermal explant and recombination experiments demonstrate that the effect of nickel is autonomous to the ectoderm, another feature in common with indirect developers. However, H. erythrogramma is distinctly sinistralized rather than ventralized, its cells shifting toward a left-side fate (vestibular ectoderm). This geometric contrast in the midst of pervasive functional similarity suggests that nickel-sensitive processes in H. erythrogramma axial patterning, homologous to those in indirect developers, have been redeployed, and hence co-opted, from their ancestral role in DV axis determination to a new role in LR axis determination. We discuss DV and LR axial patterning and their evolutionary transformation.

Animals↗