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PubMed2003

TGF-beta signaling in human skeletal and patterning disorders.

Members of the transforming growth factor beta (TGF-beta) family of multifunctional peptides are involved in almost every aspect of development. Model systems, ranging from genetically tractable invertebrates to genetically engineered mice, have been used to determine the mechanisms of TGF-beta signaling in normal development and in pathological situations. Furthermore, mutations in genes for the ligands, receptors, extracellular modulators, and intracellular signaling molecules have been associated with several human disorders. The most common are those associated with the development and maintenance of the skeletal system and axial patterning. This review focuses on the mechanisms of TGF-beta signaling with special emphasis on the molecules involved in human disorders of patterning and skeletal development.

Body Patterning↗
PubMed2001

Homology and evolutionary novelty in the deployment of extracellular matrix molecules during pigment pattern formation in the salamanders Taricha torosa and T. rivularis (Salamandridae).

Salamander larvae exhibit a diverse array of pigment patterns shortly after hatching. Previous studies have identified roles for the extracellular matrix and lateral line sensory system in promoting the development of a phylogenetically common pattern of horizontal melanophore stripes. In contrast, salamanders in the genus Taricha exhibit evolutionarily derived pigment patterns and pattern-forming mechanisms. Taricha torosa larvae exhibit compact melanophore stripes that develop via redundant, lateral line-independent mechanisms, whereas T. rivularis larvae lack stripes and instead have melanophores uniformly distributed over the flank. In this study, I test roles for candidate patterning molecules of the extracellular matrix in promoting the development of species-specific pigment patterns in Taricha. I show that tenascin deposition is negatively correlated with melanophore distributions both intraspecifically and interspecifically: this matrix molecule is present where melanophores do not localize in T. torosa and is absent from these same regions where melanophores are abundant in T. rivularis. Embryological manipulations further indicate that transient expression of tenascin in a prospective interstripe region of T. torosa reflects a phylogenetically conserved effect of lateral line development. Finally, anti-laminin immunoreactivity is negatively correlated with melanophore distributions in T. torosa, and this species exhibits a general retardation of extracellular matrix development that may allow persistent, evolutionarily novel melanophore motility in this species. Together these findings identify tenascin and laminin, or molecules co-regulated with these matrix components, as candidates for promoting early larval pigment pattern development in Taricha.

Animals↗
PubMed1998

Specification of the hindbrain fate in the zebrafish.

We determine the timing of neural commitment by hindbrain tissue in the zebrafish using microsurgical transplantation. When transplanted at shield stage to the ventral side of the embryo, presumptive hindbrain cells are not committed, as they can adapt to their environment and give rise to epidermis. In contrast, when transplanted at 80% epiboly, hindbrain cells retain their neural fate and express neural-specific antigens. Moreover, they are able to maintain regional fate, as is evident by the expression of the hindbrain-specific marker, Krox20. In addition, we observe that committed hindbrain tissues are able to induce presumptive ventral epidermis to form neural crest derivatives, otic vesicles, and neural tissues. We propose that hindbrain progenitors have acquired regional identity as a group at 80% epiboly even before making vertical contact with axial mesoderm. These results suggest that planar induction may constitute a significant component in the zebrafish neural patterning pathway.

Animals↗
PubMed1998

The Toll pathway is required in the epidermis for muscle development in the Drosophila embryo.

The Toll signaling pathway functions in several Drosophila processes, including dorsal-ventral pattern formation and the immune response. Here, we demonstrate that this pathway is required in the epidermis for proper muscle development. Previously, we showed that the zygotic Toll protein is necessary for normal muscle development; in the absence of zygotic Toll, close to 50% of hemisegments have muscle patterning defects consisting of missing, duplicated and misinserted muscle fibers (Halfon, M.S., Hashimoto, C., and Keshishian, H., Dev. Biol. 169, 151-167, 1995). We have now also analyzed the requirements for easter, spätzle, tube, and pelle, all of which function in the Toll-mediated dorsal-ventral patterning pathway. We find that spätzle, tube, and pelle, but not easter, are necessary for muscle development. Mutations in these genes give a phenotype identical to that seen in Toll mutants, suggesting that elements of the same pathway used for Toll signaling in dorsal-ventral development are used during muscle development. By expressing the Toll cDNA under the control of distinct Toll enhancer elements in Toll mutant flies, we have examined the spatial requirements for Toll expression during muscle development. Expression of Toll in a subset of epidermal cells that includes the epidermal muscle attachment cells, but not Toll expression in the musculature, is necessary for proper muscle development. Our results suggest that signals received by the epidermis early during muscle development are an important part of the muscle patterning process.

Animals↗
PubMed2006

Variation in body composition of female big brown bats (Eptesicus fuscus) during lactation.

Most small mammals support the nutritional requirements of milk production by increasing food intake. However, when nutrient intake is low, maternal body reserves may be mobilized to maintain adequate milk output. We examined patterns of body composition, including dry matter, fat, protein, and mineral content in big brown bats, Eptesicus fuscus, during lactation. Concentrations of fat and phosphorus were markedly lower in lactating mothers during week three of lactation than during the first two weeks, but these constituents rebounded to previous levels in the fourth and fifth week. Rapid recovery from fat depletion suggests that females are able to adjust to changes in demands for energy. The decrease in phosphorus during mid-lactation suggests bone demineralization, but an interspecific comparison of adult concentrations of minerals prevalent in bone suggests that mineral concentrations may never reach critically low levels in reproductively active females.

Animals↗
PubMed2003

Evidence for Notch-mediated lateral inhibition in organizing butterfly wing scales.

Here I present gene expression data that implicate a Notch-mediated lateral inhibition process in the spatial organization of butterfly wing scales. During early pupal development the receptor molecule Notch is expressed in a grid-like pattern in the wing epithelium, resulting in parallel rows of uniformly spaced cells with low Notch expression. Previous work has shown that these low-Notch cells express a homolog of the achaete-scute proneural transcription factors and develop into scales. All of these observations are consistent with the Drosophila model of Notch-mediated bristle determination and support the hypothesis that bristles and scales share an underlying patterning mechanism.

Animals↗
PubMed1988

The Dieter's Inventory of Eating Temptations: a measure of weight control competence.

This research reports the development and initial investigation of the reliability and validity of the Dieter's Inventory of Eating Temptations (DIET), a self-report inventory designed to assess behavioral competence in six types of situations related to weight control: (a) overeating, (b) negative emotions, (c) exercise, (d) resisting temptation, (e) positive social, and (f) food choice. The scales were shown to have adequate test-retest reliability and internal consistency. A comparison of 193 normal weight and 168 overweight subjects showed that overweights rated themselves as less competent in the overeating, negative emotions, and exercise situations. As a further validation, DIET scores were compared with measures of eating style derived from self-monitoring records. All of the DIET scales were significantly associated with specific parameters of eating behavior. In order to identify subtypes of overweight and normal weight individuals, cluster analyses were performed. Normal weight and overweight subjects could be grouped into interpretable clusters based on their profile of DIET scores. These data suggest that there is a relationship between eating patterns and body weight, and that there may be several types of problem behavior patterns. Treatment programs should combined assessment of behavioral competency in energy balance situations with intensive skill training in areas where situation specific competency deficits are found.

Adult↗
PubMed2006

Gap peptides: A new way to control embryonic patterning?

Gap genes encode transcription factors involved in the patterning of the head-tail axis of insect embryos. In this issue of Cell, Savard et al. (2006) identify a beetle gap gene, mille-pattes, that encodes an unusual polycistronic transcript predicted to produce four conserved peptides. These results have interesting implications for the control of embryonic patterning in insects.

Animals↗
PubMed2005

The Drosophila shell game: patterning genes and morphological change.

What are the mechanisms that convert cell-fate information into shape changes and movements, thus creating the biological forms that comprise tissues and organs? Tubulogenesis of the Drosophila dorsal eggshell structures provides an excellent system for studying the link between patterning and morphogenesis. Elegant genetic and molecular analyses from over a decade provide a strong foundation for understanding the combinatorial signaling events that specify dorsal anterior cell fates within the follicular epithelium overlying the oocyte. Recent studies reveal the morphogenetic events that alter that flat epithelial sheet into two tubes; these tubes form the mold for synthesizing the dorsal appendages--eggshell structures that facilitate respiration in the developing embryo. This review summarizes the mutant analyses that give insight into these patterning and morphogenetic processes.

Animals↗
PubMed2006

Heading in a new direction: implications of the revised fate map for understanding Xenopus laevis development.

Amphibian embryos have served as a model system for vertebrate axial patterning for more than a century. Recent changes to the Xenopus laevis fate map revised the assignment of the embryonic dorsal/ventral (back-to-belly) axis in pre-gastrula embryos and allowed the assignment of the rostral/caudal (head-to-tail) axis for the first time. Revising the embryonic axes after many years of experimentation changes our view of axial patterning in amphibians. In this review, we discuss the revised maps and axes, and show by example how the new map alters the interpretation of three experiments that form the foundations of amphibian embryology. We compare the revised amphibian fate map to the general maps of the protochordates, and discuss which features of the maps and early development are shared by chordates and which distinguish vertebrates. Finally, we offer an explanation for the formation of both complete and incomplete axes in the rescue assays routinely used to study axial patterning in Xenopus, and a model of amphibian axial patterning.

Animals↗
PubMed2002

Cellular patterning of the vertebrate embryo.

Recent studies show that cell dispersal is a widespread phenomenon in the development of early vertebrate embryos. These cell movements coincide with major decisions for the spatial organization of the embryo, and they parallel genetic patterning events. For example, in the central nervous system, cell dispersal is first mainly anterior-posterior and subsequently dorsal-ventral. Thus, genes expressed in signaling centers of the embryo probably control cell movements, tightly linking cellular and genetic patterning. Cell dispersal might be important for the correct positioning of cells and tissues involved in intercellular signaling. The emergence of cell dispersal at the onset of vertebrate evolution indicates a shift from early, lineage-based cellular patterning in small embryos to late, movement-based cellular patterning of polyclones in large embryos. The conservation of the same basic body plan by invertebrate and vertebrate chordates suggests that evolution of the embryonic period preceding the phylotypic stage was by intercalary co-option of basic cell activities present in the ancestral metazoan cell.

Animals↗
PubMed1999

Selective targeting of somatostatin receptor 3 to neuronal cilia.

Recently, five members of the somatostatin receptor family have been cloned. However, little is known about their cellular and subcellular localization in the central nervous system. Using specific anti-peptide antisera, we observed somatostatin receptor 3-like immunoreactivity in many brain regions, including the cerebral cortex, hippocampus, hypothalamus, amygdala and cerebellum. In all of these regions (except for the cerebellar cortex), somatostatin receptor 3-like immunoreactivity was selectively targeted to 4-8-microm-long rod-shaped profiles which did not co-localize with axonal or dendritic markers. One immunoreactive profile was always associated with one neuronal cell body. This staining pattern was resistant to colchicine treatment and showed a closely overlapping distribution with somatostatin receptor 3 messenger RNA, suggesting that the receptor protein is not transported over long distances. Electron microscopic analysis revealed that somatostatin receptor 3-like immunoreactivity is localized to the plasma membrane of neuronal cilia which extended into an intercellular pocket and showed a 9+0 filament pattern in their basal body and proximal segments. Thus, somatostatin receptor 3 demonstrates a unique example of a G-protein-coupled receptor not localized to "classical" pre- or postsynaptic sites, but selectively targeted to neuronal cilia. The presence of the somatostatin receptor 3 receptor on neuronal cilia suggests that these presumably non-motile cilia may not merely represent developmental remnants, but rather function as chemical sensors of the immediate milieu.

Amino Acid Sequence↗
PubMed2002

Modeling pattern formation: counting to two in the Drosophila egg.

The EGF receptor pathway patterns the Drosophila egg and specifies the position of its dorsal appendages. A new mathematical analysis of this patterning network has highlighted its crucial features and provided novel insights into the spatial and temporal kinetics controlling patterning.

Animals↗
PubMed2003

The genes orthodenticle and hunchback substitute for bicoid in the beetle Tribolium.

In Drosophila, the morphogen Bicoid organizes anterior patterning in a concentration-dependent manner by activating the transcription of target genes such as orthodenticle (otd) and hunchback (hb), and by repressing the translation of caudal. Homologues of the bicoid gene have not been isolated in any organism apart from the higher Dipterans. In fact, head and thorax formation in other insects is poorly understood. To elucidate this process in a short-germband insect, I analysed the function of the conserved genes orthodenticle-1 (otd-1) and hb in the flour beetle Tribolium castaneum. Here I show that, in contrast to Drosophila, Tribolium otd-1 messenger RNA is maternally inherited by the embryo. Reduction of Tribolium otd-1 levels by RNA interference (RNAi) results in headless embryos. This shows that otd-1 is required for anterior patterning in Tribolium. As in Drosophila, Tribolium hb specifies posterior gnathal and thoracic segments. The head, thorax and the anterior abdomen fail to develop in otd-1/hb double-RNAi embryos. This phenotype is similar to that of strong bicoid mutants in Drosophila. I propose that otd-1 and hb are part of an ancestral anterior patterning system.

Animals↗
PubMed2000

Primary mesenchyme cell-ring pattern formation in 2D-embryos of the sea urchin.

Primary mesenchyme cell (PMC) migration during PMC-ring pattern formation was analyzed using computer-assisted time-lapse video microscopy in spread embryos (2D-embryo) of the sea urchin, Mespilia globulus, and a computer simulation. The PMC formed a near normal ring pattern in the 2D-embryos, which were shown to be an excellent model for the examination of cell behavior in vivo by time-lapse computer analysis. The average migration distance of the ventro-lateral PMC aggregate-forming cells (AFC) and that of the dorso-ventral PMC cable-forming cells (CFC) showed no significant difference. All PMC took a rather straightforward migration path to their destinations with little lag time after ingression. This in vivo cell behavior fitted well to a computer simulation with a non-diffusable chemotaxis factor in the cyber-cell migration field. This simulation suggests that PMC recognize their destination from a very early moment of cell migration from the vegetal plate, and implicates that a chemoattractive region is necessary for making the PMC migration pattern. The left- and right-lateral AFC and dorso and ventral CFC were each derived from an unequally divided one-quarter segment of the vegetal plate. This suggests that AFC and CFC have a distinctive ancestor in the vegetal plate, and the PMC are a heterogeneous population at least in terms of their destination in the PMC-ring pattern.

Animals↗