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Fibroblast growth factor receptors (FGFRs) and their roles in limb development.

Fibroblast growth factor (FGF) receptors constitute a family of four membrane-spanning tyrosine kinases (FGFR1-4) which serve as high-affinity receptors for 17 growth factors (FGF1-17). To study functions of FGF/ FGFR signals in development, mice that carry mutations in each receptor have been created by gene targeting. Analysis of these mutant mice revealed essential functions of FGF receptors in multiple biological processes, including mesoderm induction and patterning, cell growth and migration, organ formation and bone growth. In this review we discuss recent work with FGF receptors to illustrate mechanisms, through which the FGF/FGFR signals specify vertebrate limb initiation, outgrowth and patterning.

Animals↗

Mode transitions in a model reaction-diffusion system driven by domain growth and noise.

Pattern formation in many biological systems takes place during growth of the underlying domain. We study a specific example of a reaction-diffusion (Turing) model in which peak splitting, driven by domain growth, generates a sequence of patterns. We have previously shown that the pattern sequences which are presented when the domain growth rate is sufficiently rapid exhibit a mode-doubling phenomenon. Such pattern sequences afford reliable selection of certain final patterns, thus addressing the robustness problem inherent of the Turing mechanism. At slower domain growth rates this regular mode doubling breaks down in the presence of small perturbations to the dynamics. In this paper we examine the breaking down of the mode doubling sequence and consider the implications of this behaviour in increasing the range of reliably selectable final patterns.

Animals↗

Selective visual attention for ugly and beautiful body parts in eating disorders.

Body image disturbance is characteristic of eating disorders, and current treatments use body exposure to reduce bad body feelings. There is however little known about the cognitive effects of body exposure. In the present study, eye movement registration (electroculography) as a direct index of selective visual attention was used while eating symptomatic and normal control participants were exposed to digitalized pictures of their own body and control bodies. The data showed a decreased focus on their own 'beautiful' body parts in the high symptomatic participants, whereas inspection of their own 'ugly' body parts was given priority. In the normal control group a self-serving cognitive bias was found: they focused more on their own 'beautiful' body parts and less on their own 'ugly' body parts. When viewing other bodies the pattern was reversed: high symptom participants allocated their attention to the beautiful parts of other bodies, whereas normal controls concentrated on the ugly parts of the other bodies. From the present findings the hypothesis follows that a change in the processing of information might be needed for body exposure to be successful.

Adult↗

Phyllotaxis--a new chapter in an old tale about beauty and magic numbers.

Phyllotaxis, the regular arrangement of leaves and flowers around the stem, is one of the most fascinating patterning phenomena in biology. Numerous theoretical models, that are based on biochemical, biophysical and other principles, have been proposed to explain the development of the patterns. Recently, auxin has been identified as the inducer of organ formation. An emerging model for phyllotaxis states that polar auxin transport in the plant apex generates local peaks in auxin concentration that determine the site of organ formation and thereby the different phyllotactic patterns found in nature. The PIN proteins play a primary role in auxin transport. These proteins are localized in a polar fashion, reflecting the directionality of polar auxin transport. Recent evidence shows that most aspects of phyllotaxis can be explained by the expression pattern and the dynamic subcellular localization of PIN1.

Body Patterning↗

Planar signalling is not sufficient to generate a specific anterior/posterior neural pattern in pseudoexogastrula explants from Xenopus and Triturus.

Early observations on the morphology of total exogastrulae from urodeles (Axolotl) had provided evidence for essential vertical signalling mechanisms in the process of neural induction. Conversely, more recent studies with anurans (Xenopus laevis) making use of molecular markers for neural-specific gene expression appear to support the idea of planar signalling as providing sufficient information for neural differentiation along the anterior-posterior axis. In an attempt to resolve this apparent contradiction, we report on the comparative analysis of morphology and gene expression characteristics with explants prepared from both urodeles (Triturus alpestris) and anurans (Xenopus laevis). For this purpose, we have made use of a refined experimental protocol for the preparation of exogastrulae that is intended to combine the advantages of the Holtfreter type exogastrula and the Keller sandwich techniques, and which we refer to as pseudoexogastrula explants. Analysis of histology and expression of several neural and ectodermal marker genes in such explants suggests that neural differentiation is induced in both species, but only within the intermediate zone between ectoderm and endomesoderm. Therefore, experiments with Xenopus and Triturus explants described in this communication argue against planar signalling events as being sufficient to generate a specific anterior/posterior neural pattern.

Animals↗

New insights into segmentation and patterning during vertebrate somitogenesis.

Understanding how muscles and the skeleton develop is essential to understanding how distinct form arises in different vertebrate organisms. The meristic somites give rise to the serially-repeated precursors of the axial skeleton and musculature. Recent studies of somitogenesis have shed light upon the mechanisms of segmentation in vertebrates and the relationship between segmentation and patterning. Significant advances have also been made in connecting signalling molecules that possess somite patterning activity with downstream effector genes.

Animals↗

Developmental complexities of simple leaves.

Recent papers have explored early events in the development of simple leaves. Functional compartmentalization of the shoot apical meristem correlates with distinct fields of cells connected by plasmodesmata. Molecules important in the initiation of phyllotactic pattern are described and the relationship between dorsoventral patterning and lateral leaf expansion is investigated.

Body Patterning↗

Skeletal dysplasias caused by a disruption of skeletal patterning and endochondral ossification.

Identification of a number of the genes that cause skeletal dysplasias has helped clinicians to provide accurate diagnoses, genetic counseling, and pre-natal diagnosis for this complex group of disorders. This review considers how some of the recent advances in human and murine genetics have led to an increased understanding of normal bone development and, in particular, the processes of skeletal patterning and endochondral ossification.

Animals↗

Patterning the vertebrate heart.

The mammalian heart is crafted from a few progenitor cells that are subject to rapidly changing sets of instructions from their environment and from within. These instructions cause them to migrate, expand and diversify in lineage, and acquire form and function. Molecular information from various model systems, combined with increasingly detailed morphogenetic data, has provided insights into some of these key events. Many congenital heart abnormalities might arise from defects in the early stages of heart development, therefore it is important to understand the molecular pathways that underlie the lineage specification and patterning processes that shape this organ.

Animals↗

Evolution of danio pigment pattern development.

Pigment patterns of danio fishes are emerging as a useful system for studying the evolution of developmental mechanisms underlying adult form. Different closely related species within the genera Danio and Devario exhibit a range of pigment patterns including horizontal stripes, vertical bars, and others. In this review, I summarize recent work identifying the genetic and cellular bases for adult pigment pattern formation in the zebrafish Danio rerio, as well as studies of how these mechanisms have evolved in other danios. Together, these analyses highlight the importance of latent precursors at post-embrynoic stages, as well as interactions within and among pigment cell classes, for both pigment pattern development and evolution.

Animals↗

Patterning of the murine dentition by homeobox genes.

Homeobox genes have been shown to be important for the regulation of pattern formation of many systems during embryogenesis. Overlapping domains of Hox gene expression in the paraxial mesoderm have been suggested to create a combinatorial code of expression (Hox code) specifying the structures of individual segments such as the vertebrae. Hox genes are not expressed in the neural crest cells contributing to tooth formation, and so a Hox code can not be involved in patterning the dentition. It has previously been proposed that other, non-Hox homeobox genes may pattern the dentition. Expression data in this paper shows that there is a pattern of overlapping domains of homeobox gene expression in facial mesenchyme prior to the initiation of tooth development. We propose that expression of these genes constitutes an odontogenic homeobox code which patterns the dentition.

Animals↗

Specification of the zebrafish nervous system by nonaxial signals.

The organizer of the amphibian gastrula provides the neurectoderm with both neuralizing and posteriorizing (transforming) signals. In zebrafish, transplantations show that a spatially distinct transformer signal emanates from tissues other than the organizer. Cells of the germring (nonaxial mesendoderm) posteriorized forebrain progenitors when grafted nearby, resulting in an ectopic hindbrain-like structure; in contrast, cells of the organizer (axial mesendoderm) caused no posterior transformation. Local application of basic fibroblast growth factor, a candidate transformer in Xenopus, caused malformation but not hindbrain transformation in the forebrain. Thus, the zebrafish gastrula may integrate spatially distinct signals from the organizer and the germring to pattern the neural axis.

Animals↗

Genetic control of branching morphogenesis.

The genetic programs that direct formation of the treelike branching structures of two animal organs have begun to be elucidated. In both the developing Drosophila tracheal (respiratory) system and mammalian lung, a fibroblast growth factor (FGF) signaling pathway is reiteratively used to pattern successive rounds of branching. The initial pattern of signaling appears to be established by early, more global embryonic patterning systems. The FGF pathway is then modified at each stage of branching by genetic feedback controls and other signals to give distinct branching outcomes. The reiterative use of a signaling pathway by both insects and mammals suggests a general scheme for patterning branching morphogenesis.

Animals↗

The C. elegans LIM homeobox gene lin-11 specifies multiple cell fates during vulval development.

LIM homeobox family members regulate a variety of cell fate choices during animal development. In C. elegans, mutations in the LIM homeobox gene lin-11 have previously been shown to alter the cell division pattern of a subset of the 2 degrees lineage vulval cells. We demonstrate multiple functions of lin-11 during vulval development. We examined the fate of vulval cells in lin-11 mutant animals using five cellular markers and found that lin-11 is necessary for the patterning of both 1 degrees and 2 degrees lineage cells. In the absence of lin-11 function, vulval cells fail to acquire correct identity and inappropriately fuse with each other. The expression pattern of lin-11 reveals dynamic changes during development. Using a temporally controlled overexpression system, we show that lin-11 is initially required in vulval cells for establishing the correct invagination pattern. This process involves asymmetric expression of lin-11 in the 2 degrees lineage cells. Using a conditional RNAi approach, we show that lin-11 regulates vulval morphogenesis. Finally, we show that LDB-1, a NLI/Ldb1/CLIM2 family member, interacts physically with LIN-11, and is necessary for vulval morphogenesis. Together, these findings demonstrate that temporal regulation of lin-11 is crucial for the wild-type vulval patterning.

Animals↗

Developmental regulation of the Hox genes during axial morphogenesis in the mouse.

The Hox genes confer positional information to the axial and paraxial tissues as they emerge gradually from the posterior aspect of the vertebrate embryo. Hox genes are sequentially activated in time and space, in a way that reflects their organisation into clusters in the genome. Although this co-linearity of expression of the Hox genes has been conserved during evolution, it is a phenomenon that is still not understood at the molecular level. This review aims to bring together recent findings that have advanced our understanding of the regulation of the Hox genes during mouse embryonic development. In particular, we highlight the integration of these transducers of anteroposterior positional information into the genetic network that drives tissue generation and patterning during axial elongation.

Animals↗

Specification of ectoderm restricts the size of the animal plate and patterns neurogenesis in sea urchin embryos.

The animal plate of the sea urchin embryo becomes the apical organ, a sensory structure of the larva. In the absence of vegetal signaling, an expanded and unpatterned apical organ forms. To investigate the signaling that restricts the size of the animal plate and patterns neurogenesis, we have expressed molecules that regulate specification of ectoderm in embryos and chimeras. Enhancing oral ectoderm suppresses serotonergic neuron differentiation, whereas enhancing aboral or ciliary band ectoderm increases differentiation of serotonergic neurons. In embryos in which vegetal signaling is blocked, Nodal expression does not reduce the size of the thickened animal plate; however, almost no neurons form. Expression of BMP in the absence of vegetal signaling also does not restrict the size of the animal plate, but abundant serotonergic neurons form. In chimeras in which vegetal signaling is blocked in the entire embryo, and one half of the embryo expresses Nodal, serotonergic neuron formation is suppressed in both halves. In similar chimeras in which vegetal signaling is blocked and one half of the embryo expresses Goosecoid (Gsc), serotonergic neurons form only in the half of the embryo not expressing Gsc. We propose that neurogenesis is specified by a maternal program that is restricted to the animal pole by signaling that is dependent on nuclearization of beta-catenin and specifies ciliary band ectoderm. Subsequently, neurogenesis in the animal plate is patterned by suppression of serotonergic neuron formation by Nodal. Like other metazoans, echinoderms appear to have a phase of neural development during which the specification of ectoderm restricts and patterns neurogenesis.

Animals↗

The roles of hedgehog and engrailed in patterning adult abdominal segments of Drosophila.

We present evidence that hedgehog (hh) protein secreted by posterior compartment cells plays a key role in patterning the posterior portion of the anterior compartment in adult abdominal segments. Loss of function of hh in the hh(ts2) mutant causes the loss of posterior tergite characteristics in the anterior compartment, whereas ectopic expression driven by hs-hh or the gain-of-function allele hh(Mir) causes transformation of anterior structures toward the posterior. FLP-out hh-expressing clones in the anterior compartment induce surrounding wild-type cells to produce posterior tergite structures, establishing that hh functions nonautonomously. The effects of pulses of ectopic expression driven by hs-hh indicate that bristle type and pigmentation are patterned by hh at widely different times in pupal development. We also present evidence that the primary polarization of abdominal segments is symmetric. This symmetry is strikingly revealed by ectopic expression of engrailed (en). As expected, this transforms anterior compartment cells to posterior compartment identity. In addition, however, ectopic en expression causes an autonomous reversal of polarity in the anterior portion of the anterior compartment, but not the posterior portion. By determining the position of polarity reversal within en-expressing clones, we were able to define a cryptic line of symmetry that lies within the pigment band of the normal tergite. This line appears to be retained in hh(ts2) mutants raised at the restrictive temperature, suggesting it is not established by hh signaling. We argue that the primary role of hh in controlling polarity is to cause anterior compartment cells to reverse their interpretation of an underlying symmetric polarization. Consistent with this, we find that strong ectopic expression of hh causes mirror-symmetric double posterior patterning, whereas hh loss of function can cause mirror-symmetric double anterior patterning.

Abdomen↗

sog and dpp exert opposing maternal functions to modify toll signaling and pattern the dorsoventral axis of the Drosophila embryo.

The short gastrulation (sog) and decapentaplegic (dpp) genes function antagonistically in the early Drosophila zygote to pattern the dorsoventral (DV) axis of the embryo. This interplay between sog and dpp determines the extent of the neuroectoderm and subdivides the dorsal ectoderm into two territories. Here, we present evidence that sog and dpp also play opposing roles during oogenesis in patterning the DV axis of the embryo. We show that maternally produced Dpp increases levels of the I(kappa)B-related protein Cactus and reduces the magnitude of the nuclear concentration gradient of the NF(kappa)B-related Dorsal protein, and that Sog limits this effect. We present evidence suggesting that Dpp signaling increases Cactus levels by reducing a signal-independent component of Cactus degradation. Epistasis experiments reveal that sog and dpp act downstream of, or in parallel to, the Toll receptor to reduce translocation of Dorsal protein into the nucleus. These results broaden the role previously defined for sog and dpp in establishing the embryonic DV axis and reveal a novel form of crossregulation between the NF(kappa)B and TGF(beta) signaling pathways in pattern formation.

Animals↗