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Characterization of epithelial domains in the nasal passages of chick embryos: spatial and temporal mapping of a range of extracellular matrix and cell surface molecules during development of the nasal placode.

The formation of the nasal passages involves complex morphogenesis and their lining develops a spatially ordered pattern of differentiation, with distinct domains of olfactory and respiratory epithelium. Using antibodies to the neural cell adhesion molecule (N-CAM), keratan sulphate and heparan sulphate proteoglycan (HSPG) and a panel of lectins (agglutinins of Canavalia ensiformis (ConA), Dolichos biflorus (DBA), peanut (PNA), Ricinis communis (RCA1), soybean (SBA), Ulex europaeus (UEA1), and wheatgerm (WGA], we have documented cell surface characteristics of each epithelial domain. Binding of antibodies to N-CAM and to keratan sulphate, and the lectins ConA, PNA, RCA1, SBA and WGA marks the olfactory epithelial domain only. The restriction of N-CAM to the sensory region of the epithelium has also been reported in the developing ear. This striking similarity is consistent with the idea that N-CAM may be involved in the division of functionally and histologically distinct cell groups within an epithelium. We traced the olfactory-specific cell markers during development to gain insights into the origin of the epithelial lining of the nasal passages. All reagents bind at early stages to the thickened nasal placode and surrounding head ectoderm and then become progressively restricted to the olfactory domain. The expression of these characteristics appears to be modulated during development rather than being cell autonomous. The distribution of keratan sulphate was compared with collagen type II in relation to the specification of the chondrocranium. Keratan sulphate and collagen type II are only colocalized at the epithelial-mesenchymal interface during early nasal development. At later stages, only collagen type II is expressed at the interface throughout the nasal passages, whereas keratan sulphate is absent beneath the respiratory epithelium.

Animals↗

Expression of the chicken GATA factor family during early erythroid development and differentiation.

The DNA motif WGATAR has been identified within transcriptional regulatory domains of globin and other erythroid-specific genes and the activator proteins that bind to this regulatory element, the GATA factors, belong to a multi-gene family that is expressed in chicken erythroid cells. Here we show that, as in chickens, multiple members of the GATA factor family are expressed in human and murine erythroid cells. During the early stages of chicken embryogenesis (well before blood island formation), each of the GATA family members is transcribed with a unique temporal and spatial pattern. In the primitive erythroid lineage, transcription of the embryonic epsilon-globin gene parallels GATA-1 expression while the switch to beta-globin transcription in definitive erythroid cells is directly preceded by a pronounced increase in GATA-3 accumulation. The timing and pattern of expression of these different mRNAs during avian erythroid development and differentiation suggests that temporally regulated changes in GATA factor expression are required for vertebrate hematopoiesis.

Animals↗

Regulation of gene transcription in the epididymis.

The epididymis exhibits region-specific as well as cell-specific patterns of gene expression within the epithelium. The spatial and temporal patterns of gene expression originate during development and are critical to the formation and maintenance of a fully functional epididymis. Despite the number of mechanisms reported to contribute to the regulation of eukaryotic gene expression, little is known about the specific mechanisms involved in the control of epididymal gene expression. This review will outline some of the cis-DNA elements and associated transcription factors that have been identified in the epididymis, in addition to discussing the potential role of co-regulator molecules and changes in chromatin structure as critical control points of gene expression. Although gene expression can be controlled at several points, discussion will focus on gene regulation at the transcriptional level. The role of post-transcriptional control, with particular attention to mRNA stability, will also be discussed.

Animals↗

Pax genes and their role in organogenesis.

Pax genes have been cloned on the basis of their homology to the Drosophila segmentation gene paired. They share a common domain, the paired domain, that is sufficient to mediate sequence-specific DNA binding. Thus far, nine members have been characterized, which exhibit highly restricted temporal and spatial expression patterns. The analysis of mouse mutants has revealed their crucial role in the formation of a variety of tissues. In particular, they are involved in the regulation of early steps in organ development. They act to define the regional specification of distinct germ layers.

Animals↗

Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif.

We have investigated the regulation of the activin-inducible distal element (DE) of the Xenopus goosecoid promoter. The results show that paired-like homeodomain transcription factors of the Mix family, Mixer and Milk, but not Mix.1, mediate activin/TGF-beta-induced transcription through the DE by interacting with the effector domain of Smad2, thereby recruiting active Smad2/Smad4 complexes to the Mixer/Milk-binding site. We identify a short motif in the carboxyl termini of Mixer and Milk, which is demonstrated to be both necessary and sufficient for interaction with the effector domain of Smad2 and is required for mediating activin/TGF-beta-induced transcription. This motif is not confined to these homeodomain proteins, but is also present in the Smad2-interacting winged-helix proteins Xenopus Fast-1, human Fast-1, and mouse Fast-2. We demonstrate directly that transcription factors of different DNA-binding specificity recruit activated Smads to distinct promoter elements via a common mechanism. These observations, together with the temporal and spatial expression patterns of Mixer and Milk, lead us to propose a model for mesoendoderm formation in Xenopus in which these homeodomain transcription factor/Smad complexes play a role in initiating and maintaining transcription of target genes in response to endogenous activin-like signals.

Activins↗

Color-flow Doppler sonography in the identification of ulcerative plaques in patients with high-grade carotid artery stenosis.

PURPOSE: To assess the ability of color-flow Doppler sonography (CFDS) to detect plaque ulcerations in patients who had high-grade to thread-like carotid artery stenosis and who underwent carotid endarterectomy. METHODS: CFDS is a noninvasive diagnostic technique that allows, in addition to spatial visualization of blood flow, the identification of abnormal blood flow patterns such as vortex formation. There is evidence that pathologic anatomic changes in the vascular wall (such as ulcerations) may result in characteristic hemodynamic alterations. Therefore, solely hemodynamic criteria (detection of vortices) were used to diagnose ulceration. The results of preoperative examinations were compared to the intraoperative findings in 89 patients in a prospective and blinded way. RESULTS: CFDS proved highly sensitive (95.3%), specific (93.5%), and accurate (94.0%) for demonstrating ulcerative plaques. CONCLUSION: CFDS may be of significant advantage for examining plaque morphology in patients who have high-grade internal carotid artery stenosis, and in whom accurate, noninvasive diagnosis of plaque ulceration was previously difficult, if not impossible.

Aged↗

The development of the pattern of growth.

It is proposed that the varying patterns of growth in development can be viewed as an aspect of pattern formation, and that different growth programmes are specified at an early stage. This is illustrated largely with respect to the development and growth of the chick wing. The spatial pattern of cellular differentiation and programme for growth can be considered in terms of the concept of positional information. The lengths of the cartilaginous elements are determined by the initial length of the primordium and its later growth, involving cell multiplication enlagement and matrix secretion. It seems that tissues have a high degree of autonomy with respect to differentiation and growth after they have had their position specified. The cellular basis of programmed growth is discussed.

Animals↗

Tenascin may not be required for intestinal villus development.

Tenascin, a large extracellular matrix protein, is subject to complex spatial and temporal patterns of expression in the course of various organogenetic processes including the formation of the small intestinal villus. In the present study, the presence of tenascin was analyzed in human fetal colonic villi, which are transient structures that are programmed to disappear at the time of colonic mucosal remodeling. While the labeling of muscles and peripheral mesenchyme was similar in both segments, surprisingly the colonic villus cores were mostly devoid of tenascin as opposed to those of the small intestine. Western blot analysis revealed that the 220 and 320 kDa forms of tenascin were detected in both segments. However, the 200 kDa form present in small intestinal villi was absent in colonic villi. These data suggest that tenascin under its 200 kDa form is not required for villus formation.

Blotting, Western↗

Pattern formation and growth during floral organogenesis: HUELLENLOS and AINTEGUMENTA are required for the formation of the proximal region of the ovule primordium in Arabidopsis thaliana.

Our understanding of the molecular mechanisms that regulate and integrate the temporal and spatial control of cell proliferation during organ ontogenesis, particularly of floral organs, continues to be primitive. The ovule, the progenitor of the seed, of Arabidopsis thaliana has been used to develop an effective model system for the analysis of plant organogenesis. A typical feature of a generalized ovule is the linear arrangement of at least three distinct elements, the funiculus, chalaza and nucellus, along a proximal-distal axis. This pattern is supposed to be established during the early proliferative phase of ovule development. We provide genetic evidence that the young ovule primordium indeed is a composite structure. Two genes, HUELLENLOS and AINTEGUMENTA have overlapping functions in the ovule and differentially control the formation of the central and proximal elements of the primordium. The results indicate that proximal-distal pattern formation in the Arabidopsis ovule takes place in a sequential fashion, starting from the distal end. Furthermore, we show that HUELLENLOS also regulates the initiation and/or maintenance of integument and embryo sac ontogenesis and interestingly prevents inappropriate cell death in the young ovule.

Arabidopsis↗

Role of mitotic, pro-apoptotic and anti-apoptotic factors in human kidney development.

The expression pattern of mitotic Ki-67 and anti-apoptotic bcl-2 proteins, as well as apoptotic caspase-3 and p53 proteins, were investigated in the human mesonephros and metanephros of 5-9 week-old human conceptuses. Apoptotic cells were additionally detected using the terminal deoxynucleotidyl transferase (TdT) nick-end labelling (TUNEL) method. Between the 5th and 7th developmental weeks Ki-67, caspase-3 and TUNEL-positive cells characterized all mesonephric structures, indicating importance of cell proliferation in the growth of the mesonephros and role of apoptosis in nephrogenesis. From the 7th week on, p53 and bcl-2 positive cells appeared in the mesonephros as well. Regressive changes in the mesonephros could be regulated by activation of p53, while bcl-2 could contribute to selective survival of some tubules giving rise to adult structures. In the early human metanephros (5-7 weeks), Ki-67 positive cells characterized all metanephric structures, indicating a role of cell proliferation in branching of the ureteric bud and in nephron formation. During the same period bcl-2, caspase-3 and TUNEL-positive cells were found only in the metanephric mesenchyme and nephrons. Bcl-2 protein probably protected nephrons from apoptosis, while caspase-3 protein controlled cell death in the mesenchyme. At later stages (7-9-weeks), appearance of p53-expressing cells could participate in further morphogenesis of the metanephric collecting system. The factors investigated had a spatially and temporally restricted pattern of appearance in developing kidneys. Changes in that pattern might lead to serious disturbances of kidney formation and function in early childhood.

Apoptosis↗

A cellular oscillator model for periodic pattern formation.

In this paper, we present a model for pattern formation in developing organisms that is based on cellular oscillators (CO). An oscillatory process within cells serves as a developmental clock whose period is tightly regulated by cell autonomous or non-autonomous mechanisms. A spatial pattern is generated as a result of an initial temporal ordering of the cell oscillators freezing into spatial order as the clocks slow down and stop at different times or phases in their cycles. We apply a CO model to vertebrate somitogenesis and show that we can reproduce the dynamics of periodic gene expression patterns observed in the pre-somitic mesoderm. We also show how varying somite lengths can be generated with the CO model. We then discuss the model in view of experimental evidence and its relevance to other instances of biological pattern formation, showing its versatility as a pattern generator.

Animals↗

Spatial and temporal distribution of Indian hedgehog mRNA in the embryonic mouse mandible.

Hedgehog genes are involved in pattern formation during embryonic development. A recent report showed that Sonic hedgehog is expressed in the mouse mandible in the presumptive incisor region. In the present study, Indian hedgehog (Ihh) transcripts were present from gestational day 9 to 14 in the mouse mandible (reverse transcription/polymerase chain reaction analysis). Ihh mRNA was present in the dental lamina in both incisor and molar regions and in the developing whiskers (in-situ hybridization). Ihh may be involved in the site-specific proliferation of mandibular epithelium during the formation of the dental lamina. This is consistent with the observation that endogenous synthesis of retinoic acid is necessary for the initiation of odontogenesis and that retinoic acid induces hedgehog expression.

Animals↗

A receptor protein tyrosine kinase implicated in the segmental patterning of the hindbrain and mesoderm.

Pattern formation in the hindbrain and paraxial mesoderm of vertebrates occurs by the formation of a series of repeated segments. These processes of segmentation appear different at the morphological level, since hindbrain segments, the rhombomeres, form by the subdivision of the neural epithelium into compartments, whereas the mesodermal somites form by the sequential aggregation of mesenchymal cells into epithelial balls. Previous studies have implicated genes encoding transcription factors in the development of hindbrain segments, but nothing is known of genes involved in the formation of somites. Cellular interactions and signal transduction must be an important aspect of hindbrain segmentation, so we have screened for tyrosine kinases expressed in rhombomere-restricted patterns in the developing mouse embryo. We have identified a receptor protein tyrosine kinase, Sek, that has high relative levels of expression in rhombomeres 3 and 5. This alternating pattern is established coincidentally, both spatially and temporally, with the expression of Krox-20, a zinc-finger gene expressed prior to the morphological formation of rhombomeres. In addition, Sek expression occurs in several other developing tissues, including a dynamic regulation in the developing forebrain, spinal cord, early mesoderm and anterior presomitic mesoderm (segmental plate). The latter expression occurs in two stripes that correlate with, and presage, the formation of somites. Sek expression initially occurs throughout the presumptive somite, then becomes restricted anteriorly, and finally is down-regulated as the definitive somite is formed. These data suggest that despite the morphological differences in the segmentation of the hindbrain and mesoderm, Sek is involved in the segmental patterning of both of these tissues.

Animals↗

Spontaneous pattern formation in an effectively one-dimensional dielectric-barrier discharge system

In a dielectric-barrier discharge between diametrically opposite sides of a narrow tube, discharge filaments stabilize at regular intervals along the tube's length. Three types of periodic patterns are observed, as is a disordered state in which filaments fire at apparently random positions and times. Time-resolved current measurements indicate that for each spatial pattern, a particular number of discharge stages occur during the voltage half-cycle. A preliminary model of the pattern-formation dynamics is described, motivating further work on time-resolved imaging and investigations of surface charge distributions.

Journal Article↗

Foot formation in Hydra: a novel gene, anklet, is involved in basal disk formation.

We isolated a novel gene by a differential-display RT-PCR method comparing basal disk tissue and peduncle tissue in a species of Hydra, Pelmatohydra robusta, and we referred to it as anklet. The putative anklet product has a signal sequence in its N-terminus, and it has one MAC/PF domain and one EGF domain. In normal hydra, the expression of anklet was restricted in the periphery of the basal disk and the lowest region of the peduncle. In foot-regenerating animals, anklet was first expressed in the newly differentiated basal disk gland cells at the regenerating basal end, and then expression became restricted at the periphery of the regenerated basal disk and in the lowest region of the peduncle. This spatially specific expression pattern suggested that the product of the anklet gene plays a role in basal disk formation. We therefore examined the role played by the protein product of the anklet gene by suppressing the transcription level of anklet using an RNA-mediated interference (RNAi) method. Suppression of the level of expression of the anklet gene led to a decrease in basal disk size in normal hydra, and to a delay in basal disk regeneration in foot-amputated animals. These results suggested that anklet is involved in the formation and maintenance of the basal disk in hydra.

Amino Acid Sequence↗

Localization of surface structures during procaryotic differentiation: role of cell division in Caulobacter crescentus.

Asymmetric cell division in Caulobacter crescentus produces two cell types, a stalked cell and a new swarmer cell, with characteristics surface structures. We have examined the role of the cell cycle in the differentiation of these two cells using adsorption of bacteriophage phi LC72, the assembly of the polar flagellum, and stalk formation as assays for changes in surface morphology. Previous studies of this aquatic bacterium [17,25] have suggested that the replicating chromosome acts as a "clock' in timing the formation of the flagellar filament at one pole of the new swarmer cell. the analysis of conditional cell cycle mutants presented here extends these results by showing that DNA synthesis is also required for adsorption of phage phi LC72 and, more importantly, they also suggest that a late cell division step is involved in determining the spatial pattern in which the phage receptors and flagella are assembled. We propose that this cell division step is required for formation of "organizational' centers which direct the assembly of surface structures at the new cell poles, and for the polarity reversal in assembly that accompanies swarmer cell to stalked cell development.

Bacterial Physiological Phenomena↗

A model for colour pattern formation in the butterfly wing of Papilio dardanus.

The butterfly Papilio dardanus is well known for the spectacular phenotypic polymorphism in the female of the species. We show that numerical simulations of a reaction diffusion model on a geometrically accurate wing domain produce spatial patterns that are consistent with many of those observed on the butterfly. Our results suggest that the wing coloration is due to a simple underlying stripe-like pattern of some pigment-inducing morphogen. We focus on the effect of key factors such as parameter values for mode selection, threshold values which determine colour, wing shape and boundary conditions. The generality of our approach should allow us to investigate other butterfly species. The relationship between these key factors and gene activities is discussed in the context of recent biological advances.

Animals↗

Novel marker genes for early leaf development indicate spatial regulation of carbohydrate metabolism within the apical meristem.

To identify genes expressed at the earliest stages of leaf development, we have performed a differential display analysis using portions of meristems destined to form leaves. Our analysis led to the identification of five genes showing an asymmetric pattern of gene expression within the meristem associated with leaf formation. Surprisingly, three of these genes encoded enzymes involved in carbohydrate metabolism (ADPglucose pyrophosphorylase, sucrose synthase and an SNF1-like kinase). Furthermore, specific transcript patterns were responsive to specific sugar and hormonal treatments. The other two genes identified encoded a Phantastica-like myb transcription factor (associated with the acquisition of leaf dorsiventrality) and CYP85 (a cytochrome P450, which plays a pivotal role in brassinolide metabolism). These data, firstly, identify a novel set of marker genes for the analysis of the earliest stages of leaf formation. Secondly, the function of the proteins encoded by these genes and their expression patterns within the meristem indicate that carbohydrate metabolism is spatially regulated within a tissue involved in key developmental processes. Finally, our data provide the first indication of an asymmetry in gene expression related to hormone biosynthesis in the meristem.

Amino Acid Sequence↗