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PubMed1997

Hyaluronan is a prerequisite for ductal branching morphogenesis.

Hyaluronan, a macromolecular carbohydrate polymer of the extracellular matrix is prominent early in embryogenesis, coinciding with rapid tissue growth. CD44, the predominant receptor for hyaluronan on vertebrate cells, is a variably expressed transmembrane glycoprotein. Mouse anterior prostate glands obtained at various postnatal time points were examined for the expression of hyaluronan and CD44. Reverse transcriptase polymerase chain reaction analysis was used to map the temporal regulation of specific CD44 variant isoforms. In each age group, hyaluronan was localized exclusively in the stromal matrix. Hyaluronan was greatly reduced in the later ages and was entirely absent around the developmentally quiescent proximal regions of the ducts. Early in prostate development, CD44 was prominent in the mesenchyme. However, in the later phases, CD44 expression became associated with membranes of epithelial cells. The role of hyaluronan-CD44 interactions in ductal branching morphogenesis was studied by serum-free organ culture of mouse anterior prostate. In the presence of optimal levels of testosterone, the organs underwent ductal branching morphogenesis. Treatment with either neutralizing anti-CD44 antibodies, hyaluronan hexasaccharides or the enzyme hyaluronidase inhibited androgen-stimulated ductal branching morphogenesis. These results are suggestive of the significant role played by hyaluronan-CD44 interactions in mediating androgen-induced prostatic growth and morphogenesis.

Animals↗
PubMed1998

Muscle and tendon morphogenesis in the avian hind limb.

The proper development of the musculoskeletal system in the tetrapod limb requires the coordinated development of muscle, tendon and cartilage. This paper examines the morphogenesis of muscle and tendon in the developing avian hind limb. Based on a developmental series of embryos labeled with myosin and tenascin antibodies in whole mount, an integrative description of the temporal sequence and spatial pattern of muscle and tendon morphogenesis and their relationship to cartilage throughout the chick hind limb is presented for the first time. Anatomically distinct muscles arise by the progressive segregation of muscle: differentiated myotubes first appear as a pair of dorsal and ventral muscle masses; these masses subdivide into dorsal and ventral thigh, shank and foot muscle masses; and finally these six masses segregate into individual muscles. From their initial appearance, most myotubes are precisely oriented and their pattern presages the pattern of future, individual muscles. Anatomically distinct tendons emerge from three tendon primordia associated with the major joints of the limb. Contrary to previous reports, comparison of muscle and tendon reveals that much of their morphogenesis is temporally and spatially closely associated. To test whether reciprocal muscle-tendon interactions are necessary for correct muscle-tendon patterning or whether morphogenesis of each of these tissues is autonomous, two sets of experiments were conducted: (1) tendon development was examined in muscleless limbs produced by coelomic grafting of early limb buds and (2) muscle development was analyzed in limbs where tendon had been surgically altered. These experiments demonstrate that in the avian hind limb the initial morphogenetic events, formation of tendon primordia and initial differentiation of myogenic precursors, occur autonomously with respect to one another. However, later morphogenetic events, such as subdivision of muscle masses and segregation of tendon primordia into individual tendons, do require to various degrees reciprocal interactions between muscle and tendon. The dependence of these later morphogenetic events on tissue interactions differs between different proximodistal regions of the limb.

Animals↗
PubMed2000

Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis.

Morphogenesis of the mouse lung involves reciprocal interactions between the epithelial endoderm and the surrounding mesenchyme, leading to an invariant early pattern of branching that forms the basis of the respiratory tree. There is evidence that Fibroblast growth factor 10 (Fgf10) and Bone Morphogenetic Protein 4 (Bmp4), expressed in the distal mesenchyme and endoderm, respectively, play important roles in branching morphogenesis. To examine these roles in more detail, we have exploited an in vitro culture system in which isolated endoderm is incubated in Matrigel(TM) substratum with Fgf-loaded beads. In addition, we have used a Bmp4(lacZ) line of mice in which lacZ faithfully reports Bmp4 expression. Analysis of lung endoderm in vivo shows a dynamic pattern of Bmp4(lacZ) expression during bud outgrowth, extension and branching. In vitro, Fgf10 induces both proliferation and chemotaxis of isolated endoderm, whether it is derived from the distal or proximal lung. Moreover, after 48 hours, Bmp4(lacZ) expression is upregulated in the endoderm closest to the bead. Addition of 30-50 ng/ml of exogenous purified Bmp4 to the culture medium inhibits Fgf-induced budding or chemotaxis, and inhibits overall proliferation. By contrast, the Bmp-binding protein Noggin enhances Fgf-induced morphogenesis. Based on these and other results, we propose a model for the combinatorial roles of Fgf10 and Bmp4 in branching morphogenesis of the lung.

Animals↗
PubMed1992

Collagen-induced rapid morphogenesis of human mammary epithelial cells: the role of the alpha 2 beta 1 integrin.

The cell line MTSV1-7, originally derived by immortalizing mammary epithelial cells cultured from human milk was able to form three-dimensional structures in collagen gel. We have now found that these cells, cultured as a monolayer, are able to undergo rapid morphogenesis forming ridges and balls around collagen fibres, when soluble collagen type I is added to the medium. Monoclonal antibodies to the alpha 2 (P1E6) and beta 1- (mAB13) subunits of VLA-2, but not to the alpha 3-subunit (P1B5) of VLA-3, could block this collagen-induced rapid morphogenesis (CIRM). The effect of the antibodies on cell attachment, spreading, and migration on collagen gels was analyzed to identify alpha 2 beta 1 dependent steps which might be involved in CIRM. The results suggest that while other proteins, besides alpha 2 beta 1, are also involved in cell attachment and migration, cell spreading was specifically blocked by antibodies to the VLA-2, but not to the VLA-3 integrin. The results demonstrate that the alpha 2 beta 1 integrin plays a crucial role in the collagen-induced morphogenesis of human mammary epithelial cells and implicate the process of VLA-2-dependent cell spreading as an important step in this morphogenesis.

Antibodies, Monoclonal↗
PubMed2002

Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2.

Epithelial-mesenchymal interactions during lung development require extracellular signaling factors that facilitate branching morphogenesis. We show here that matrix metalloproteinases (MMPs) originating in the mesenchyme are necessary for epithelial branching and alveolization. We found that the delayed lung maturation characterized by abnormal branching and poor alveolization seen in mice deficient in epidermal growth factor receptor (Egfr(-/-)) is accompanied by aberrant expression of MMPs. By in situ zymography, the lungs from newborn Egfr(-/-) mice had low gelatinolytic activity compared with wildtype. Inhibition of MMPs in developing lungs in vivo or in vitro severely retarded morphogenesis. Egfr(-/-) mice had low expression of MT1-MMP/MMP14, which is a potent activator of gelatinase A/MMP2, in their lungs. Egf ligand increased MT1-MMP mRNA by tenfold in lung fibroblasts from wild type, but not from Egfr(-/-) mice. Extracts from lungs of Egfr(-/-) mice showed a tenfold reduction in active MMP-2, but only a slight decrease in proMMP-2 by zymography. At birth, MMP-2(-/-) mice had a lung phenotype characterized by abnormal lung alveolization which phenocopied that of Egfr(-/-) mice, albeit somewhat less severe. We conclude that proteolysis mediates epithelial/mesenchymal interactions during lung morphogenesis. From the phenotypes of the Egfr(-/-) mice, we identify MT1-MMP as a major downstream target of Egfr signaling in lung in vivo and in vitro. MT1-MMP is, in turn, necessary for activation of MMP-2, a mesenchymal enzyme that is required for normal lung morphogenesis.

Animals↗
PubMed1999

Inhibition of vascular endothelial cell morphogenesis in cultures by limbal epithelial cells.

PURPOSE: To study the in vitro angiogenic activity of human conjunctival and limbal epithelial cells and conjunctival, limbal, and corneal fibroblasts in a three-cell-type coculture model. METHODS: Human umbilical vein endothelial cells (EC) were cocultured with epithelial cells, fibroblasts, or epithelial cells and fibroblasts to test their effect on EC morphogenesis. Neutralizing antibodies to some known angiogenic factors were added to the culture to see whether the EC morphogenesis may be blocked by a particular antibody. RESULTS: Conjunctival and limbal epithelial cells exhibited very little or no stimulatory effect on EC tube formation when examined in an EC- epithelial cell coculture system. In contrast, conjunctival, limbal, and corneal fibroblasts all promoted EC morphogenesis when examined under the same culture conditions. Fibroblast-induced EC morphogenesis was inhibited by addition of anti-vascular endothelial growth factor (VEGF) and/or anti-basic fibroblast growth factor (bFGF) antibodies to the culture medium. In the three-cell-type coculture system consisting of ECs, fibroblasts, and epithelial cells, limbal epithelial cells (but not conjunctival epithelial cells) exhibited a strong inhibitory effect on fibroblast-induced EC tube formation. CONCLUSIONS: The proangiogenic activity of ocular surface fibroblasts is probably mediated through a paracrine mechanism by VEGF and bFGF. Limbal epithelial cells, but not conjunctival epithelial cells, inhibit fibroblast-stimulated angiogenesis.

Adolescent↗
PubMedDate not supplied

Epithelial-mesenchymal interactions in tooth morphogenesis: the roles of extracellular matrix, growth factors, and cell surface receptors.

Morphogenesis and cell differentiation in the developing tooth are controlled by a series of reciprocal interactions between the epithelial and mesenchymal tissues. The exact molecular mechanisms operating in these interactions are unknown at present, but both structural components of the extracellular matrix (ECM) and diffusible growth factors have been suggested to be involved. In this review article we summarize our findings on the distribution patterns of three ECM molecules and two cell surface receptors during tooth morphogenesis through bud, cap, and bell stages of development. The examined molecules include fibronectin, type III collagen, and tenascin, which all represent components of the mesenchymal ECM, the cell surface proteoglycan, syndecan, which functions as a receptor for interstitial matrix, and the cell surface receptor for epidermal growth factor. Based on the observed changes in distribution patterns and on experimental evidence, roles are suggested for these molecules in epithelial-mesenchymal interactions during tooth development. Fibronectin is suggested to be involved in the cell-matrix interaction that controls odontoblast differentiation. Epidermal growth factor and its receptors are suggested to be involved in a paracrine fashion in the epithelial-mesenchymal interactions regulating morphogenesis of bud- and cap-stage teeth. Tenascin and syndecan are accumulated in the dental mesenchyme during the bud stage of development, and it is suggested that they represent a couple of a cell surface receptor and its matrix ligand and that they are involved in mesenchymal cell condensation during the earliest stages of tooth morphogenesis.

Animals↗
PubMed1989

[Genetic control of morphogenesis of Pseudomonas aeruginosa transposable phage D3112].

The influence of ts mutations in the early and late genes of transposable phage D3112 on phage morphogenesis was studied. The mutations in the early genes A, B and C were shown to suppress morphogenesis of D3112. Six genes (D, E, F, G, H and I), located from 14 to 29 kbp of the phage physical map, control morphogenesis of phage head. Five genes (J, K, L, M and N), clustered in the 29-36 kbp region of the map, control morphogenesis of tail. The similarity of genetic organization of the Escherichia coli transposable phage Mu and the Pseudomonas aeruginosa phage D3112 is discussed.

Bacteriophages↗
PubMed1989

Early embryonic mouse mandibular morphogenesis and cytodifferentiation in serumless, chemically defined medium: a model for studies of autocrine and/or paracrine regulatory factors.

During craniofacial and mandibular development at least three interdependent processes become integrated: 1) regulation of time-dependent differential gene expression; 2) positional information resulting in pattern formations; and 3) morphogenesis. The present studies were designed to test the hypothesis that intrinsic and/or paracrine factors regulate the developmental program for embryonic mouse mandibular morphogenesis, histogenesis, and cytodifferentiation. Either E11 or E12 C57B110 (B10.A) strain mouse mandibular processes were cultured in serumless, chemically defined medium for periods up to 9 days in vitro. At selected stages of development 3H-thymidine incorporation into DNA was used to evaluate the mitotic labeling for selected tissue compartments. Macroscopic observations demonstrated that morphogenesis (shape/form) in vitro was comparable to that for in vivo controls. Histological results demonstrated that chondrogenesis, osteogenesis, tooth formation, tongue formation, lip formation, and epithelial differentiation with keratinization were expressed according to sequence, time, and positions comparable to those observed in controls. This experimental approach provided datasets to support the hypothesis that exogenous long-range factors are not required for embryonic mouse mandibular morphogenesis and further suggested that autocrine and/or paracrine factors mediate the timing and position of mandibular development.

Animals↗
PubMed1993

Collagen-induced morphogenesis and expression of the alpha 2-integrin subunit is inhibited in c-erbB2-transfected human mammary epithelial cells.

The c-erbB2 (or Her2) oncogene is amplified and/or overexpressed in a significant proportion of breast cancers. To assess the role of the c-erbB2 oncogene in mammary tumorigenesis, we have transfected the corresponding human c-erbB2 cDNA into an immortalized human mammary epithelial cell line, MTSV1-7, that was derived from luminal epithelial cells cultured from milk. Three transfectants expressing different levels of the c-erbB2 gene product have been isolated which form colonies in agar and produce tumours in nude mice with high efficiency. We have observed that MTSV1-7 cells form three-dimensional structures in collagen gels and that alpha 2 beta 1-integrin plays a crucial role in the process of morphogenesis. We now find that the c-erbB2 transfectants exhibit an impaired ability to undergo morphogenesis in collagen gels as compared with the parental cell line or the control neomycin transfectant, and that the degree of impairment is related to the level of c-erbB2 expression. Moreover, overexpression of the c-erbB2 product was found to be correlated with a specific decrease in the expression of alpha 2-integrin subunit and in the alpha 2-mRNA. The breast cancer cell line SKBr3, which carries multiple copies of the c-erbB2 gene and overexpresses the 185-kDa product, was also found to express very low levels of the alpha 2-integrin protein and mRNA. Our results confirm the involvement of the alpha 2 beta 1-integrin in collagen-induced morphogenesis of mammary epithelial cells and suggest that the c-erbB2 gene product may inhibit this morphogenesis by inhibiting the expression of the alpha 2-integrin subunit.

Breast↗
PubMed1996

Keratinocyte growth factor (KGF) can replace testosterone in the ductal branching morphogenesis of the rat ventral prostate.

Prostatic growth occurs through ductal elongation and branching into the mesenchyme. Ductal branching morphogenesis in the prostate is elicited by androgens via mesenchymal-epithelial interactions mediated by paracrine influences from mesenchyme. The role of keratinocyte growth factor (KGF) was investigated in the developing prostate as KGF has been suggested to be a paracrine acting factor. KGF transcripts were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in neonatal rat ventral prostates (VPs) in vivo, in VPs cultured in vitro, and in isolated VP mesenchyme. KGF receptor was detected in VP's by RT-PCR and was localized specifically to the epithelium by in situ hybridization. KGF was investigated as a potential paracrine mediator during androgen-induced prostatic development by examining neonatal rat VPs cultured for 6 days under serum-free conditions using a basal medium supplemented only with insulin and transferrin. When testosterone (10(-9) to 10(-8) M) was added to the basal medium, VPs grew and underwent ductal branching morphogenesis similar to that in situ. Neutralization of endogenous KGF with a monoclonal antibody to KGF (anti-KGF) or a soluble KGF receptor peptide inhibited androgen-stimulated VP growth (DNA content) and reduced the number of ductal end buds after 6 days of culture. When KGF (50 or 100 ng/ml) was added to the basal medium in the absence of testosterone, VP growth and ductal branching morphogenesis were stimulated. The number of ductal end buds was about 70% of that obtained with an optimal dose of testosterone (10(-8)M), and DNA content of VP's cultured with 100 ng/ml KGF was equivalent to that of glands cultured with testosterone. The stimulatory effect of KGF was partially blocked by cyproterone acetate, a steroidal anti-androgen. These data imply that KGF plays an important role as a mesenchymal paracrine mediator of androgen-induced epithelial growth and ductal branching morphogenesis in the rat VP.

Animals↗
PubMed1997

Organ cultures of embryonic rat tongue support tongue and gustatory papilla morphogenesis in vitro without intact sensory ganglia.

Taste buds on the mammalian tongue are confined to the epithelium of three types of gustatory papillae: the fungiform, circumvallate, and foliate. The gustatory papillae are composed of an epithelium that covers a broad connective tissue core, with extensive innervation to taste bud and nongustatory epithelial locations. Although the temporal sequence of gustatory papilla development is known for several species, factors that regulate initiation, growth, and maintenance of the papillae are not understood. We tested the hypothesis that sensory innervation is required for the initial formation and early morphogenesis of fungiform papillae in a patterned array. An organ culture of the embryonic rat tongue was developed to provide an in vitro system for studying mechanisms involved in fungiform papilla morphogenesis in patterns on the anterior tongue. Tongues were dissected from embryos at 13 days of gestation (E13), a time when the tongue has not yet fully formed and gustatory papillae have not yet appeared, and at 14 days of gestation (E14), when the tongue is well formed and papillae make their initial morphological appearance. Dissected tongues were maintained at the gas/liquid interface in standard organ culture dishes, fed with DMEM/F12 plus 2% B-27 supplement and 1% fetal bovine serum. After 1, 2, 3, or 6 days in culture, tongues were processed for scanning electron or light microscopy, or immunocytochemistry. Tongues cultured from E13 or E14 underwent extensive morphogenesis and growth in vitro. Furthermore, fungiform papillae developed on these tongues on a culture day equivalent to E15 in vivo; that is, after 2 days for cultures begun at E13 and 1 day for those begun at E14. Because E15 is the characteristic time for gustatory papilla formation in the intact embryo, results demonstrate that the cultured tongues retain important temporal information related to papilla development. In addition, fungiform papillae formed in the tongue cultures in the stereotypic pattern of rows. The papillae were large structures with epithelial and mesenchymal cell integrity, and an intact epithelial basement membrane was indicated with laminin immunoreactivity. The cultures demonstrate that gustatory papilla morphogenesis can progress in the absence of an intact sensory innervation. To exclude a potential developmental role for autonomic ganglion cells that are located in the posterior rat tongue, cultures consisting of only the anterior half of E14 tongues were established. Fungiform papilla development progressed in half tongues in a manner directly comparable to whole tongue cultures. Therefore, robust, reproducible development of fungiform papillae in patterns is supported in rat tongue cultures from E13 or E14, without inclusion of intact sensory or major, posterior tongue autonomic ganglia. This is direct evidence that papillae will form and develop further in vitro without sensory ganglion support. The data also provide the first detailed account of in vitro development of the entire embryonic tongue.

Animals↗
PubMed1998

Cartilage-derived morphogenetic proteins and cartilage morphogenesis.

Cartilage morphogenesis is a prerequisite for skeletal development and maintenance. The morphogenesis of cartilage determines the shape of bones, and joints including articular cartilage, ligaments, and tendon. This article reviews the recent advances in cartilage-derived morphogenetic proteins (CDMPs) and related bone morphogenetic proteins (BMPs). Cartilage-derived morphogenetic proteins (CDMPs) are related to BMPs and are critical for cartilage and joint morphogenesis. Cartilage morphogenesis is a multistep cascade that includes factors for initiation, promotion, and maintenance of cartilage phenotype. The extracellular matrix of cartilage consists of a constellation of macromolecules such as collagens, proteoglycans, and glycoproteins. Morphogens bind to extracellular matrix components and assemble a morphogenetic scaffold. Recent advances in CDMPs may aid in articular cartilage repair and regeneration.

Animals↗
PubMed1998

Cell morphogenesis in Arabidopsis.

Cell morphogenesis encompasses all processes required to establish a three-dimensional cell shape. Cells acquire the architecture specific to their developmental context by using the spatial information provided by internal or external cues. As a response to these signals, cells become reorganized and establish functionally distinct subcellular domains that ultimately lead to morphological changes. In its simplest form, cell morphogenesis results in the establishment of asymmetry along one axis, a cell polarity. Although cell polarity has been studied intensively in budding yeast and epithelial cells, little is known about more complex modes of cell morphogenesis involving multiple axes. In this review we compare the regulation of cell morphogenesis of different genetically well-characterized cell types in Arabidopsis thaliana.

Arabidopsis↗
PubMed2001

Laminin-1 and alpha6beta1 integrin regulate acinar morphogenesis of normal and malignant human prostate epithelial cells.

BACKGROUND: Cell-matrix interactions via integrin receptors are critical for acinar morphogenesis. The non-tumorigenic, human prostate epithelial cell line RWPE-1 was used in a three-dimensional (3D) cell culture model to identify the matrix protein and its integrin receptor required for acinar morphogenesis. METHODS: 3D cultures, immunostaining, confocal microscopy, and Western blot analysis were used to examine acinar formation on matrix proteins and to determine integrin receptor expression. RESULTS: RWPE-1 cells differentiate into acini of polarized cells with a distinct lumen in 3D Matrigel culture. In contrast, the malignant WPE1-NB26 prostate epithelial cells form solid cell masses. In 3D gels of laminin-1, type IV collagen, or fibronectin, RWPE-1 cells form acini only in laminin-1. Anti-laminin-1 antibody reduces acinar formation in a dose-dependent manner. Polarized RWPE-1 cells showed basal expression of alpha6 and beta1 integrin subunits. Blocking antibodies to alpha6 or beta1 reduced acinar formation to 9 and 6 percent of control, respectively. The beta1 integrin colocalized with focal adhesion kinase (FAK). Inhibition of extracellular signal-regulated kinase kinase activity significantly reduced acinar formation to 38 percent of control, suggesting that beta1 integrin-mediated signal transduction may be regulated through a FAK pathway. CONCLUSIONS: While basal expression of alpha6beta1 integrin in RWPE-1 cells correlates with their ability to polarize and form acini, a decrease or loss of alpha6, and diffused beta1 expression in WPE1-NB26 cells correlates with loss of acinar-forming ability. Results show that laminin-1 and a functional alpha6beta1 integrin receptor are required for acinar morphogenesis. This novel 3D cell culture model is useful for elucidating regulation of acinar morphogenesis and its loss during prostate carcinogenesis.

Antibodies↗
PubMed2001

Spatial and temporal patterns of morphogenesis of hippocampal pyramidal cells: study in the early postnatal rat.

Several studies have dealt with the morphogenesis of the rat hippocampal pyramidal cell, but little is known about how the different pyramidal cell shapes of CA fields differentiate from neuroepithelial cells, or about how the field morphological identity emerges. From our studies of pyramidal cell shapes in the CA1, CA3, and CA4 fields of hippocampi at postnatal developmental stages between P0 and P12, using fresh semidissociated slices and acutely dissociated cells, we identified the sequence of cell shape transformation by which they differentiate from simple bipolar to complex shapes characteristic of adult pyramidal cells of CA1 and CA3. Pyramidal cell morphogenesis does not occur synchronously throughout the CA hippocampus fields, but cells in the CA4 field undergo morphological differentiation at earlier stages, prenatally, than CA3 cells, and these in turn earlier than CA1 cells. Thus, during the P1-P6 stages, a gradient of shapes from less to greater differentiation was clearly observed from CA1 to CA4 in a single slice. Furthermore, a mixture of cells at different degrees of differentiation is observed in CA1 from P1 to P10, and in CA3 from P1 to P5. A gradient of shapes from more to less differentiation was observed at stages P5-P6 from septal to temporal. We describe two processes in the pyramidal cell morphogenesis in the CA1 and CA3 fields, the approximation to the soma of the point of bifurcation of the main apical process, and the acquisition of triangular shape of the soma, showing by a quantitative study of both processes that they occur earlier in CA3 than in CA1. Our study, therefore, provides new insight into rat pyramidal cell morphogenesis, and indicates that this process might be differently regulated in the various CA fields. Hippocampus

Animals↗
PubMed1995

Three-dimensional localization of wild-type and myosin II mutant cells during morphogenesis of Dictyostelium.

Dictyostelium amoebae that lack myosin II (mhcA-) are unable to undergo morphogenesis. The cells aggregate slowly to form hemispherical mounds, but the mounds never extend a tip upward. Expression of developmentally regulated genes appears normal in the absence of morphogenesis. When mixed with an excess of wild-type cells, some mutant cells form differentiated spores; however, rescue is extremely inefficient (Knecht and Loomis, 1988). In order to assess how morphogenesis is normally accomplished and why mutants lacking myosin II cannot develop, a new method has been developed that allows individual amoebae to be localized and tracked at high resolution within the multicellular organism during development. Amoebae are labeled with a fluorescent dye at the beginning of starvation, mixed with an excess of unlabeled cells, and allowed to develop. The three-dimensional position of labeled cells in the multicellular organism is then determined using a laser scanning confocal microscope. Using this methodology, we have shown that labeled wild-type cells are randomly distributed throughout the organism and complete development normally. When labeled mhcA- mutant cells are mixed with a 20-fold excess of wild-type cells, they are non-randomly localized even at the earliest stages of development. Mutant cells in aggregation streams are found primarily at the edges of the streams and many cells never become part of the streams or are left behind as the wild-type cells complete aggregation. Those that are incorporated into the aggregate are found at the edge and base, the backs of slugs and the base of the fruiting bodies. A few mutant cells can be found in the sorus, where they presumably become spores. The segregation of mhcA- mutant cells to the outside of the wild-type aggregation streams argues that the mutant cells are unable to penetrate a mass of adhered, wild-type cells. We hypothesize that mutant cells lacking cortical integrity are unable to generate sufficient protrusive force to break the adhesion of wild-type cells to each other. This would make the mutants incapable of moving through a mass of cells (either mutant or wild type) or of changing shape when adhered to other cells. We propose that mutants lacking myosin II are unable to accomplish morphogenesis because they cannot move correctly in a three-dimensional mass of adhered cells.

Animals↗
PubMed2005

Biomedicine and diseases: the Klippel-Trenaunay syndrome, vascular anomalies and vascular morphogenesis.

Vascular morphogenesis is a vital process for embryonic development, normal physiologic conditions (e.g. wound healing) and pathological processes (e.g. atherosclerosis, cancer). Genetic studies of vascular anomalies have led to identification of critical genes involved in vascular morphogenesis. A susceptibility gene, VG5Q (formally named AGGF1), was cloned for Klippel-Trenaunay syndrome (KTS). AGGF1 encodes a potent angiogenic factor, and KTS-associated mutations enhance angiogenic activity of AGGF1, defining 'increased angiogenesis' as one molecular mechanism for the pathogenesis of KTS. Similar studies have identified other genes involved in vascular anomalies as important genes for vascular morphogenesis, including TIE2, VEGFR-3, RASA1, KRIT1, MGC4607, PDCD10, glomulin, FOXC2, NEMO, SOX18, ENG, ACVRLK1, MADH4, NDP, TIMP3, Notch3, COL3A1 and PTEN. Future studies of vascular anomaly genes will provide insights into the molecular mechanisms for vascular morphogenesis, and may lead to the development of therapeutic strategies for treating these and other angiogenesis-related diseases, including coronary artery disease and cancer.

Angiogenic Proteins↗