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Results for “Spatial pattern formation”

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PubMed1997

Three-dimensional reconstruction of colon carcinoma metastases in liver.

Resection of liver metastases in patients with colon cancer increases survival but success depends on removal of all tumour tissue. For this purpose, understanding of spatial relationships between metastases and liver architecture is essential. Because metastatic cancer growth is essentially a three-dimensional (3D) event, we decided to apply 3D reconstruction techniques to study these spatial relationships between metastases and liver structures such as blood vessels, stroma and the liver capsule (Glisson's capsule). Colon carcinoma metastases were experimentally induced in rat liver by injection of colon cancer cells (CC531) into the portal vein. Three weeks later, livers from these animals and control livers were removed and immediately frozen in liquid nitrogen. Thirty-seven to 110 consecutive sections were used for each 3D reconstruction of 26 metastases in eight livers. Contours of different structures were stained by (immuno)histochemical means, traced in each section and stored in a database. From the contour model, a volume model was generated. Among the 26 metastases, seven were found to grow distantly from the liver capsule. They were small and consisted of well-differentiated cancer cells that were totally surrounded by a basement membrane and stroma which was always connected with adjacent blood vessels of a portal tract. The remaining 19 metastases showed a more advanced pattern of development. Infiltration of poorly differentiated colon cancer cells progressed through the stroma at various sites and areas of direct contact between cancer cells and hepatocytes were frequently found. This type of outgrowth of cancer cells was only found when metastases had made contact with the liver capsule. However, some areas in sections of these advanced stages still resembled small metastases. On the basis of these findings, we conclude that stroma-affects the differentiation pattern of cancer cells and has at least a dual role in tumour growth. On the one hand it limits invasion of cancer cells in the surrounding host tissue. On the other hand, stroma formation at the capsule, which consists mainly of granulation tissue, facilitates outgrowth of the tumours. Furthermore, our 3D reconstructions demonstrate the spatial heterogeneity of larger metastases and the importance of a 3D approach to understand growth and development of metastases in general and colon cancer metastases in the liver in particular.

Animals↗

PubMed2002

Endogenous patterns of BMP signaling during early chick development.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta superfamily signaling molecules that play important roles in a wide variety of developmental processes. In this study, we have used an antibody specific for the phosphorylated and activated form of Smad1 to examine endogenous patterns of BMP signaling in chick embryos during early development. We find complex spatial and temporal distributions of BMP signaling that elucidate how BMPs may function in multiple patterning events in the early chick embryo. In the pregastrula embryo, we find that BMP signaling is initially ubiquitous and is extinguished in the epiblast at the onset of primitive streak formation. At the head process stage, BMP signaling is inactivated in prospective neural plate, while it is strongly activated at the neural plate border, a region which is populated by cells that will give rise to neural crest. During later development, we find a dynamic spatiotemporal activation of BMP signaling along the rostrocaudal axis, in the dorsal neural tube, in the notochord, and in the somites during their maturation process. We discuss the implication of our results for endogenous functions of BMP signaling during chick development.

Animals↗

PubMed2006

Expression of otd orthologs in the amphipod crustacean, Parhyale hawaiensis.

The arthropod head is a complex metameric structure. In insects, orthodenticle (otd) functions as a 'head gap gene' and plays a significant role in patterning and development of the anterior head ectoderm, the protocerebrum, and the ventral midline. In this study, we characterize the structure and developmental deployment of two otd paralogs in the amphipod crustacean, Parhyale hawaiensis. Photd1 is initially expressed at gastrulation through germband stages in a bilaterally symmetric, restricted region of the anterior head ectoderm and also in a single column of cells along the ventral midline. Late in embryogenesis, Photd1 is expressed within the developing anterior brain and the expression along the embryonic midline has become restricted to a stereotypic group of segmentally reiterated cells. The second ortholog Photd2, however, has a unique temporal-spatial expression pattern and is not detected until after the head lobes have been organized in the developing ectoderm of the germband during late germband stages. Anteriorly, Photd2 is coincident with the Photd1 head expression domain; however, Photd2 is not detected along the ventral midline during formation of the germband and only appears in the ventral midline late in embryonic development in a restricted group of cells distinct from those expressing Photd1. The early expression of Photd1 in the anterior head ectoderm is consistent with a role as a head gap gene. The more posterior expression of Photd1 is suggestive of a role in patterning the embryonic ventral midline. Photd2 expression appears too late to play a role in early head patterning but may contribute to latter patterning in restricted regions of both the head and the ventral midline. The comparative analysis of otd reveals the divergence of gene expression and gene function associated with duplication of this important developmental gene.

Animals↗

PubMed1993

Frames of reference in vision and language: where is above?

Spatial terms such as "above" must be used and interpreted with respect to some frame of reference. Perceptual cues for verticality were varied in four experiments to investigate whether the comprehension and production of "above" is based on a viewer-centered (deictic) frame, an environment-centered (extrinsic) frame, or an object-centered (intrinsic) frame of reference. "Above" was usually interpreted with respect to an environment-centered reference frame, but there was a significant contribution from object-centered reference frames as well; the viewer-centered reference frame made no independent contribution to "above". The meaning of "above" appears not to specify a particular reference frame; rather, selection of a reference frame during spatial assignment determines how spatial terms such as "above" and "below" will be used and interpreted.

Adult↗

PubMedDate not supplied

Evidence for a reaction-diffusion system as a mechanism controlling mammalian hair growth.

A scheme is outlined for the differentiation of epithelial cells in hair follicle bulbs which requires several spatial pattern properties characteristics of a reaction-diffusion system. Spatial patterns in the reacting and diffusing substances, called morphogens , develop spontaneously depending on the size and shape of the follicle bulb. The patterns correctly predict the cross-sectional shape of several classes of fibres known as awls , auchenes and zigzags found in mice. The spatial patterns also determine the distribution of ortho- and para-cortical cells within the fibre cross-section. In order to explain the observed variation in the morphology of zigzag fibres it is necessary to use the capacity of a reaction-diffusion system to produce spatial patterns with a preferred orientation. Moving the dermal papilla of the hair follicle bulb off-centre causes a homogeneous pattern of morphogens to become unstable and a bilateral pattern to develop with a preferred orientation. This phenomenon forms the basis of a control mechanism for the formation of zigzag fibres.

Animals↗

PubMed2005

Specification of neural precursor identity in the geophilomorph centipede Strigamia maritima.

Despite differences in the formation of neural precursors, all arthropod species analyzed so far generate about 30 single precursors (insects/crustaceans) or precursor groups (chelicerates/myriapods) per hemi-segment. In Drosophila, each precursor has a distinct identity conferred by segment polarity and dorso-ventral patterning genes that subdivide the ventral neuroectoderm into a grid-like structure. Temporal patterning mechanisms generate additional diversity after delamination from the neuroectoderm. Previous work shows that the genetic network involved in recruitment and specification of neural precursors is conserved in arthropods. However, comparative studies on generation of precursor diversity are few and partial. Here, we test whether aspects of the Drosophila model may apply in the geophilomorph centipede Strigamia maritima. We describe precursor formation, based on morphology and on Delta and Notch expression. We then show that in S. maritima, hunchback and Krüppel are expressed in subsets of neural precursors generating distinct temporal expression domains within the plane of the neuroectoderm. This expression pattern suggests that temporal changes in spatial patterning cues may result in the ordered production of different neural identities. We suggest that temporal patterning mechanisms were present in the last common ancestor of arthropods, although the regulatory interactions of transcription factors might have diverged in the lineage leading to insects.

Animals↗

PubMed1998

Histogenesis of the chequered pattern of ivory of the African elephant (Loxodonta africana).

This study aimed to propose a hypothesis on the events which lead to the development of the characteristic chequered pattern of elephant ivory. Twenty fragments of ivory and six elephant tusks were obtained through the National Parks Board of South Africa. Polished surfaces were prepared in sagittal and longitudinal planes and the characteristics of the distinctive chequered pattern described. Light- and electron-microscopical techniques and image analyses were employed to determine the morphological basis of the pattern and to describe the spatial distribution, density and morphology of the dentinal tubules. These investigations showed that the distinctive pattern was the result of the sinusoidal, centripetal course followed by dentinal tubules. The apical, slanted part of the sinusoidal curve is the result of the centripetally moving odontoblast, which, during formation of ivory, progresses towards the centre of the tusk on a decreasing circumference. It is suggested that this leads to cell crowding, increased pressure between odontoblasts and subsequent apical movement of their cell bodies, cell degeneration and fusion. Odontoblastic degeneration and fusion probably relieve the pressure between the crowded odontoblasts by reducing their numbers and the remaining odontoblasts now orientate their centripetal course towards the tip of the tusk, thereby forming the anterior-directed part of the sinusoidal path of the tubule. As odontoblasts progress centripetally the diameter of the pulpal cavity decreases further and the processes of apical movement, fusion and degeneration of odontoblasts are repeated. This occurs until the pulpal cavity is obliterated.

Anatomy, Cross-Sectional↗

PubMed1998

Waves of mouse Lunatic fringe expression, in four-hour cycles at two-hour intervals, precede somite boundary formation.

During somitogenesis, cells are recruited to the caudal presomitic mesoderm (PSM) from the primitive streak (and later the tail bud), while somites separate from the rostral end as epithelial cubes. This is a regular process, one somite forming every 2 hours in the mouse, that can be simulated by clock and wavefront models. The chick basic helix-loop-helix transcription factor encoded by c-hairy1 is expressed in dynamic waves in the PSM, undergoing one cycle for each somite formed. This is compatible with an underlying oscillating molecular clock. We have shown here that Lunatic fringe (L-fng) expression is indicative of it being one of the implementing outputs of this clock. Fringe genes regulate the Notch signalling pathway in boundary formation. Of the known mouse genes, only L-fng is expressed in PSM and it is required for somite segmentation and patterning. We have now shown that L-fng is expressed as dynamic, repetitive and complex waves within the mouse PSM. A wave takes 4 hours to complete one cycle and terminates immediately at, and prior to, somite boundary formation. Consecutive waves are temporally but not spatially overlapping, being initiated in the caudal PSM every 2 hours, so offset by one half-cycle. Waves of expression are not associated with cell movement and do not require cell contact for propagation, so appear to reflect a cell-autonomous clock that is synchronous in all PSM cells.

Animals↗

PubMed2026

Mechanisms and functional implications of long-range enhancer-dependent gene regulation.

Metazoan development relies on the coordinated establishment of diverse gene regulatory programs that drive the formation of specific cell types, tissues and organs. The temporal and spatial control of gene expression is achieved through the concerted activity of multiple classes of cis-regulatory elements encoded in the genome. Among these, enhancers enable the establishment of specific and precise gene expression patterns and control gene expression over long linear distances, a property often referred to as distance-independent regulatory activity. However, enhancer activity is, in fact, inversely correlated with linear genomic distance, and target gene expression and transcriptional precision decrease with increasing enhancer-promoter linear distances. Here, we highlight emerging insights into multiple mechanisms that enable enhancers to precisely and robustly activate gene expression across large genomic distances. Finally, we provide a more speculative perspective on the potential advantages that long-range regulation might confer during the establishment of developmental gene expression programs.

Enhancer Elements, Genetic↗

PubMed1998

Cellular and molecular partners involved in gut morphogenesis and differentiation.

The intestinal mucosa represents an interesting model to study the cellular and molecular basis of epithelial-mesenchymal cross-talk participating in the development and maintenance of the digestive function. This cross-talk involves extracellular matrix molecules, cell-cell and cell-matrix adhesion molecules as well as paracrine factors and their receptors. The cellular and molecular unit is additionally regulated by hormonal, immune and neural inputs. Such integrated cell interactions are involved in pattern formation, in proximodistal regionalization, in maintenance of a gradient of epithelial proliferation and differentiation, and in epithelial cell migration. We focus predominantly on two aspects of these integrated interactions in this paper: (i) the role of basement membrane molecules, namely laminins, in the developmental and spatial epithelial behaviour; and (ii) the importance of the mesenchymal cell compartment in these processes.

Animals↗

PubMed1992

[Vitamin D: biosynthesis, metabolism and mechanism of action at the cellular level].

The term vitamin D includes various chemical species. Vitamin D3 a true endogenous or alimentary prohormone is converted into its main metabolite, calcitriol, by successive hydroxylations in the liver in position 25 and in the kidney in position 1, the production of which is controlled by several factors including parathyroid hormone, blood calcium and phosphorus or insulin as well as by the metabolites of the hormone itself. It controls the synthesis of numerous peptides by acting on gene expression. Indeed, several structural proteins are involved including procollagen alpha 1l, core protein of proteoglycans, diverse regulatory peptides such as protooncogene c-myc and growth factors, "Tumor Necrosis Factor or TNF" and "Nerve Growth Factor or NGF" or hormones such as parathyroid hormone, and finally constitutive proteins of the mineralized tissues such as osteonectin, osteocalcin, osteopontin and calbindins. Therefore, it modulates very different cellular processes. It acts via a nuclear receptor the structure and function of which have been investigated by genetic engineering (cloning of genes encoding for the receptor and hormono-dependent peptides, transfection assays, directed mutagenesis). Actual studies investigate its role in the formation of the complex for transcription initiation near ADN sites, the "Vitamin D Responsive Element or VDRE", located upstream vitamin D-responsive genes and approximately RNA polymerase II. The receptor, which is present in many cell types at various concentrations, would determine spatial and temporal patterns of calcitriol action during development in conjunction with chromatin factors.

Cell Physiological Phenomena↗

PubMed1992

Bracteomania, an inflorescence anomaly, is caused by the loss of function of the MADS-box gene squamosa in Antirrhinum majus.

Anomalous flowering of the Antirrhinum majus mutant squamosa (squa) is characterized by excessive formation of bracts and the production of relatively few and often malformed or incomplete flowers. To study the function of squamosa in the commitment of an inflorescence lateral meristem to floral development, the gene was cloned and its genomic structure, a well as that of four mutant alleles, was determined. SQUA is a member of a family of transcription factors which contain the MADS-box, a conserved DNA binding domain. In addition, we analysed the temporal and spatial expression pattern of the squa gene. Low transcriptional activity of squa is detectable in bracts and in the leaves immediately below the inflorescence. High squa transcript levels are seen in the inflorescence lateral meristems as soon as they are formed in the axils of bracts. Squa transcriptional activity persists through later stages of floral morphogenesis, with the exception of stamen differentiation. Although necessary for shaping a normal racemose inflorescence, the squa function is not absolutely essential for flower development. We discuss the function of the gene during flowering, its likely functional redundancy and its possible interaction with other genes participating in the genetic control of flower formation in Antirrhinum.

Alleles↗

PubMed2025

Advances in tumor subclone formation and mechanisms of growth and invasion.

Tumor subclones refer to distinct cell populations within the same tumor that possess different genetic characteristics. They play a crucial role in understanding tumor heterogeneity, evolution, and therapeutic resistance. The formation of tumor subclones is driven by several key mechanisms, including the inherent genetic instability of tumor cells, which facilitates the accumulation of novel mutations; selective pressures from the tumor microenvironment and therapeutic interventions, which promote the expansion of certain subclones; and epigenetic modifications, such as DNA methylation and histone modifications, which alter gene expression patterns. Major methodologies for studying tumor subclones include single-cell sequencing, liquid biopsy, and spatial transcriptomics, which provide insights into clonal architecture and dynamic evolution. Beyond their direct involvement in tumor growth and invasion, subclones significantly contribute to tumor heterogeneity, immune evasion, and treatment resistance. Thus, an in-depth investigation of tumor subclones not only aids in guiding personalized precision therapy, overcoming drug resistance, and identifying novel therapeutic targets, but also enhances our ability to predict recurrence and metastasis risks while elucidating the mechanisms underlying tumor heterogeneity. The integration of artificial intelligence, big data analytics, and multi-omics technologies is expected to further advance research in tumor subclones, paving the way for novel strategies in cancer diagnosis and treatment. This review aims to provide a comprehensive overview of tumor subclone formation mechanisms, evolutionary models, analytical methods, and clinical implications, offering insights into precision oncology and future translational research.

Humans↗

PubMed2006

Dimensions of good and poor handwriting legibility in first and second graders: motor programs, visual-spatial arrangement, and letter formation parameter setting.

First and second graders who were good and poor handwriters completed three writing tasks: writing letters of alphabet in order from memory, letter copying in a passage, and composing on provided topics. A coding scheme was used to evaluate these dimensions of legibility: spacing between words and between letters within words, alignment (letter placement on lines), letter height, letter slant, reversals, added strokes, missing strokes, and missing letters. Although results were somewhat task dependent, most differences between good and poor handwriters involved poor handwriters generating more letters with added strokes, producing smaller letters, and exhibiting more variability in spacing and alignment. The good and poor handwriters did not differ on average performance in alignment of words on the baseline or in spacing of letters within words and spacing between words. Each of three dimensions of handwriting contributed uniquely to the handwriting of first and second graders: motor programs, visual-spatial arrangement on the written page, and letter formation parameter setting.

Chi-Square Distribution↗

PubMed1995

Requirement of the ETS domain transcription factor D-ELG for egg chamber patterning and development during Drosophila oogenesis.

The D-elg gene encodes an ETS domain transcription factor that functions in Drosophila oogenesis. D-elg belongs to a small group of genes that are required for the formation of both the anteroposterior and dorsoventral axes of the egg chamber. During oogenesis in D-elg mutant females, the spatial localization of oskar and gurken mRNAs in the oocyte is disrupted and a follicle cell enhancer trap marker identifies dorsoventral polarity defects. Also, specialized follicle cells, called border cells, fail to migrate from their anterior location to a position adjacent to the developing oocyte. Consistent with these phenotypes, D-elg shows genetic interactions with two genes required for normal egg chamber differentiation.

Animals↗

PubMed1994

Localization of CRABP-I and CRABP-II mRNA in the early mouse embryo by whole-mount in situ hybridization: implications for teratogenesis and neural development.

Retinoic acid (RA) has been implicated in vertebrate neural pattern formation. In this paper we analysed the expression patterns of the cellular retinoic acid binding proteins (CRABP-I and II) during early morphogenesis in normal and RA-treated mouse embryos by whole-mount in situ hybridization. This technique allowed a detailed analysis of the spatial and temporal changes in mRNA expression pattern. Both CRABPs were expressed in a rhombomere specific pattern; putative neural crest cells in the branchial arches expressed the CRABPs at levels corresponding to the rhombomere from which they were derived. CRABP-II, but not CRABP-I, was expressed in the neural epithelium caudal to the hindbrain. CRABP-I is strongly expressed in a fine net-like pattern which extends from the caudal diencephalon to the rostral hindbrain and remains predominantly dorsal to the lateral midline of the neural tube. This network corresponds to the pattern formed by the putative first axons of the embryonic mouse brain which are produced by the developing neurons of the mesencephalic nucleus of the trigeminal nerve. Although the expression of CRABP-I was unaffected by a teratogenic dose of RA, CRABP-II expression was increased slightly with no alteration in the normal spatial or temporal boundaries. These results support the suggestion that the CRABPs may play an important role in modulating endogenous RA levels, particularly in the developing nervous system and its neural crest derivatives. Furthermore, the limited ability of CRABP mRNA levels to respond to exogenous retinoids may be a factor in retinoid teratogenicity.

Abnormalities, Drug-Induced↗

PubMed1994

spalt encodes an evolutionarily conserved zinc finger protein of novel structure which provides homeotic gene function in the head and tail region of the Drosophila embryo.

The region specific homeotic gene spalt (sal) of Drosophila melanogaster promotes the specification of terminal pattern elements as opposed to segments in the trunk. Our results show that the previously reported sal transcription unit was misidentified. Based on P-element mediated germ line transformation and DNA sequence analysis of sal mutant alleles, we identified the transcription unit that carries sal function. sal is located close to the misidentified transcription unit, and it is expressed in similar temporal and spatial patterns during embryogenesis. The sal gene encodes a zinc finger protein of novel structure composed of three widely spaced 'double zinc finger' motifs of internally conserved sequences and a single zinc finger motif of different sequence. Antibodies produced against the sal protein show that sal is first expressed at the blastoderm stage and later in restricted areas of the embryonic nervous system as well as in the developing trachea. The antibodies detect sal homologous proteins in corresponding spatial and temporal patterns in the embryos of related insect species. Sequence analysis of the sal gene of Drosophila virilis, a species which is phylogenetically separated by approximately 60 million years, suggests that the sal function is conserved during evolution, consistent with its proposed role in head formation during arthropod evolution.

Amino Acid Sequence↗

PubMed2006

Thyroid hormone metabolism and peroxidase function in two non-chordate animals.

In mammals, thyroid hormone (TH) signaling is essential for metabolic control, differentiation and homeostasis. These hormones are also involved in the regulation of metamorphosis in amphibians and lampreys and a role in basal chordates has been suggested. Increasing evidence supports TH-related function not only in basal chordates such as urochordates and cephalochordates but also in other invertebrate groups. However, the regulatory mechanisms underlying TH function including the mechanisms of endogenous synthesis of hormones in these groups are essentially unknown. Our data provide evidence for endogenous TH synthesis in the sea hare Aplysia californica and the sea urchin Lytechinus variegatus based on thin layer chromatography. Pharmacological experiments show that these hormones accelerate development to metamorphosis and specifically affect the formation of juvenile skeletal structures in the sea urchin. Furthermore, we identified two new peroxidase genes (LvTPO from L. variegatus and AcaTPO from A. californica) showing high sequence similarity with peroxidasin and thyroid peroxidases (the critical TH synthesis enzymes found in all vertebrates). Spatial and temporal expression patterns of these transcripts suggest a role of LvTPO and AcaTPO in a variety of processes such as development to metamorphosis and the regulation of the animal's energetics. We discuss our new findings in the context of evolution of TH synthesis and TH signaling in non-chordate animals.

Animals↗