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At least 955 records · Page 53Linked to original sources
PubMed2004

Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2.

Semaphorins, originally identified as axon guidance facto s in the nervous system, play integral roles in organogenesis. Here, we demonstrate a critical involvement of Sema6D in cardiac morphogenesis. Ectopic expression of Sema6D o RNA interference against Sema6D induces expansion or narrowing of the ventricular chamber, respectively, during chick embryonic development. Sema6D also exerts region-specific activities on cardiac explants, a migration-promoting activity on outgrowing cells from the conotruncal segment, and a migration-inhibitory activity on those from the ventricle. Plexin-A1 mediates these activities as the major Sema6D-binding receptor. Plexin-A1 forms a receptor complex with vascular endothelial growth factor receptor type 2 in the conotruncal segment or with Off-track in the ventricle segment; these complexes are responsible for the effects of Sema6D on the respective regions. Thus, the differential association of Plexin-A1 with additional receptor components entitles Sema6D to exert distinct biological activities at adjacent regions. This is crucial for complex cardiac morphogenesis.

Animals↗
PubMed1998

C/EBPbeta, but not C/EBPalpha, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland.

The CCAAT/enhancer binding proteins (C/EBPs) are differentially expressed throughout mammary gland development and interact with binding sites within the promoter of a milk protein gene, beta-casein. The specific roles of C/EBPbeta and C/EBPalpha in mouse mammary gland development and differentiation have been investigated in mice that carry targeted deletions of these genes. C/EBPbeta-/- virgin mice exhibited cystic, enlarged mammary ducts with decreased secondary branching. Transplantation of C/EBPbeta-/- mammary epithelium into the cleared mammary fat pads of nude mice confirmed that this defect in ductal morphogenesis was intrinsic to the epithelium. When treated with estrogen/progesterone (E+P) to simulate pregnancy, C/EBPbeta-/- mammary glands displayed only limited lobuloalveolar development and ductal side branching. Primary mammary epithelial cells obtained from E+P-treated C/EBPbeta-/- mice that were cultured on extracellular matrix gels did not functionally differentiate in response to lactogenic hormones despite their organization into three-dimensional structures. Expression of beta-casein protein was inhibited 85%-100% and whey acidic protein (WAP) was undetectable. In contrast, no detectable alterations in mammary development or beta-casein expression were observed in mammary outgrowths derived from newborn C/EBPalpha-/- mammary epithelium transplanted into the cleared mammary fat pads of syngeneic hosts. These results demonstrate that C/EBPbeta, but not C/EBPalpha, is required for ductal morphogenesis, lobuloalveolar development, and functional differentiation of mammary epithelial cells.

Animals↗
PubMed1999

Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis.

Hrs is an early endosomal protein homologous to Vps27p, a yeast protein required for vesicular trafficking. Hrs has a FYVE double zinc finger domain, which specifically binds phosphatidylinositol(3)-phosphate and is conserved in several proteins involved in vesicular traffic. To understand the physiological role of Hrs, we generated mice carrying a null mutation of the gene. Hrs homozygous mutant embryos developed with their ventral region outside of the yolk sac, had two independent bilateral heart tubes (cardia bifida), lacked a foregut, and died around embryonic day 11 (E11). These phenotypes arise from a defect in ventral folding morphogenesis that occurs normally around E8.0. Significant apoptosis was detected in the ventral region of mutant embryos within the definitive endoderm, suggesting an important role of this germ layer in ventral folding morphogenesis. Abnormally enlarged early endosomes were detected in the mutants in several tissues including definitive endoderm, suggesting that a deficiency in vesicular transport via early endosomes underlies the mutant phenotype. The vesicular localization of Hrs was disrupted in cells treated with wortmannin, implicating Hrs in the phosphatidylinositol 3-kinase pathway of membrane trafficking.

Androstadienes↗
PubMed2006

Feedback control of morphogenesis in fungi by aromatic alcohols.

Many fungi undergo a developmental transition from a unicellular yeast form to an invasive filamentous form in response to environmental cues. Here we describe a quorum signaling pathway that links environmental sensing to morphogenesis in Saccharomyces cerevisiae. Saccharomyces cells secrete aromatic alcohols that stimulate morphogenesis by inducing the expression of FLO11 through a Tpk2p-dependent mechanism. Mutants defective in synthesis of these alcohols show reduced filamentous growth, which is partially suppressed by the addition of these aromatic alcohols. The production of these auto signaling alcohols is regulated by nitrogen: High ammonia restricts it by repressing the expression of their biosynthetic pathway, whereas nitrogen-poor conditions activate it. Moreover, the production of these aromatic alcohols is controlled by cell density and subjected to positive feedback regulation, which requires the transcription factor Aro80p. These interactions define a quorum-sensing circuit that allows Saccharomyces to respond to both cell density and the nutritional state of the environment. These same autoregulatory molecules do not evoke the morphological switch in Candida albicans, suggesting that these molecular signals are species-specific.

Cyclic AMP-Dependent Protein Kinases↗
PubMed2006

Cadherins in development: cell adhesion, sorting, and tissue morphogenesis.

Tissue morphogenesis during development is dependent on activities of the cadherin family of cell-cell adhesion proteins that includes classical cadherins, protocadherins, and atypical cadherins (Fat, Dachsous, and Flamingo). The extracellular domain of cadherins contains characteristic repeats that regulate homophilic and heterophilic interactions during adhesion and cell sorting. Although cadherins may have originated to facilitate mechanical cell-cell adhesion, they have evolved to function in many other aspects of morphogenesis. These additional roles rely on cadherin interactions with a wide range of binding partners that modify their expression and adhesion activity by local regulation of the actin cytoskeleton and diverse signaling pathways. Here we examine how different members of the cadherin family act in different developmental contexts, and discuss the mechanisms involved.

Animals↗
PubMed1989

A new look into an old problem: keratins as tools to investigate determination, morphogenesis, and differentiation in skin.

We have investigated keratin and keratin mRNA expression during (1) differentiation of stem cells into epidermis and hair follicles and (2) morphogenesis of follicles. Our results indicate that a type I keratin K14 is expressed early in embryonal basal cells. Subsequently, its expression is elevated in the basal layer of developing epidermis but suppressed in developing matrix cells. This difference represents an early and major biochemical distinction between the two diverging cell types. Moreover, because expression of this keratin is not readily influenced by extracellular regulators or cell culture, it suggests a well-defined and narrow window of development during which an irreversible divergence in basal and matrix cells may take place. In contrast to K14, which is expressed very early in development and coincident with basal epidermal differentiation, a hair-specific type I keratin and its mRNA is expressed late in hair matrix development and well after follicle morphogenesis. Besides providing an additional developmental difference between epidermal and hair matrix cells, the hair-specific keratins provide the first demonstration that keratin expression may be a consequence rather than a cause of cell organization and differentiation.

Animals↗
PubMed1993

Morphogenesis in Drosophila requires nonmuscle myosin heavy chain function.

We provide the first link between a known molecular motor and morphogenesis, the fundamental process of cell shape changes and movements that characterizes development throughout phylogeny. By reverse genetics, we generate mutations in the Drosophila conventional nonmuscle myosin (myosin II) heavy chain gene and show that this gene is essential. We demonstrate that these mutations are allelic to previously identified, recessive, embryonic-lethal zipper mutations and thereby identify nonmuscle myosin heavy chain as the zipper gene product. Embryos that lack functional myosin display defects in dorsal closure, head involution, and axon patterning. Analysis of cell morphology and myosin localization during dorsal closure in wild-type and homozygous mutant embryos demonstrates a key role for myosin in the maintenance of cell shape and suggests a model for the involvement of myosin in cell sheet movement during development. Our experiments, in conjunction with the observation that cytokinesis also requires myosin, suggest that the processes of cell shape change in morphogenesis and cell division are intimately and mechanistically related.

Animals↗
PubMed1995

Dachsous encodes a member of the cadherin superfamily that controls imaginal disc morphogenesis in Drosophila.

Mutations in the dachsous gene of Drosophila lead to striking defects in the morphogenesis of the thorax, legs, and wings. The dachsous gene has been cloned and shown to encode a huge transmembrane protein that is a member of the cadherin superfamily, similar to the fat gene reported previously. Both the Dachsous and Fat proteins contain large tandem arrays of cadherin domains--27 and 34, respectively--as compared with 4 cadherin domains in classic vertebrate cadherins. In addition, Dachsous and Fat each has a cytoplasmic domain with sequence similarity to the cytoplasmic beta-catenin-binding domain of classic vertebrate cadherins. The dachsous gene is expressed in the ectoderm of embryos, whereas its expression in larvae is restricted to imaginal discs and specific regions of the brain. The phenotypes of, and genetic interactions between dachsous and fat are consistent with a model in which cell proliferation and morphogenesis of imaginal structures depends on the coupled equilibria between homo- and heterophilic interactions of the Dachsous and Fat cadherin proteins.

Alleles↗
PubMed2004

Morphogenesis of maize embryos requires ZmPRPL35-1 encoding a plastid ribosomal protein.

In emb (embryo specific) mutants of maize (Zea mays), the two fertilization products have opposite fates: Although the endosperm develops normally, the embryo shows more or less severe aberrations in its development, resulting in nonviable seed. We show here that in mutant emb8516, the development of mutant embryos deviates as soon as the transition stage from that of wild-type siblings. The basic events of pattern formation take place because mutant embryos display an apical-basal polarity and differentiate a protoderm. However, morphogenesis is strongly aberrant. Young mutant embryos are characterized by protuberances at their suspensor-like extremity, leading eventually to structures of irregular shape and variable size. The lack of a scutellum or coleoptile attest to the virtual absence of morphogenesis at the embryo proper-like extremity. Molecular cloning of the mutation was achieved based on cosegregation between the mutant phenotype and the insertion of a MuDR element. The Mu insertion is located in gene ZmPRPL35-1, likely coding for protein L35 of the large subunit of plastid ribosomes. The isolation of a second allele g2422 and the complementation of mutant emb8516 with a genomic clone of ZmPRPL35-1 confirm that a lesion in ZmPRPL35-1 causes the emb phenotype. ZmPRPL35-1 is a low-copy gene present at two loci on chromosome arms 6L and 9L. The gene is constitutively expressed in all major tissues of wild-type maize plants. Lack of expression in emb/emb endosperm shows that endosperm development does not require a functional copy of ZmPRPL35-1 and suggests a link between plastids and embryo-specific signaling events.

Amino Acid Sequence↗
PubMed1983

Basal lamina changes during tissue interactions in hair follicles--an in vitro study of normal dermal papillae and vitamin A-induced glandular morphogenesis.

Skin pieces from 14-day fetal mice were cultivated for 1-10 days prior to fixation and sectioning. Subsequently, sections were studied by light and transmission electron microscopy. In a standard medium the lateral hair follicle walls showed progressive maturation of the basal lamina, while the hair matrix, at the time of a known tissue interaction, showed the formation of gaps in the basal lamina, with heterotypic cell contacts through the gaps. In a vitamin-A enriched medium similar changes occurred, not only at the hair matrix, but also at lateral follicle walls, at the sites of, and prior to, budding and glandular morphogenesis. This study shows that the induction of hair matrix by dermal papilla may perhaps be added to the list of normal tissue interactions in which heterotypic cell contacts occur. It also suggests that vitamin-A induced glandular morphogenesis might come about through a mechanism resembling a normal tissue interaction.

Animals↗
PubMed1998

Mammary fibroblast-derived hepatocyte growth factor stimulates growth and morphogenesis of mouse mammary tumor cells in primary culture.

We have recently isolated a mammary growth factor from the conditioned medium of mouse mammary stromal fibroblasts and identified it as a mouse homologue of human HGF (hepatocyte growth factor). To elucidate the role of HGF in mouse mammary tumorigenesis, we produced recombinant mouse HGF and examined its effects on primary cultures of mouse mammary tumor cells in this study. HGF at concentrations above 20 ng/ml maximally stimulated the growth of mammary tumor cells in primary monolayer culture. HGF also stimulated the three-dimensional growth and branching morphogenesis of mammary tumor cells cultured inside collagen gels. A comparison of the growth-stimulating activity of HGF with that of EGF (epidermal growth factor) and KGF (keratinocyte growth factor) revealed that HGF is the most potent growth factor among the three. Immunological studies using an antibody against mouse HGF demonstrated that 74% of the growth-stimulating activity present in the mammary fibroblast-conditioned medium was abolished by the antibody, indicating that HGF is the major growth factor produced by the fibroblasts. These observations thus suggest a role for HGF as a mammary stromal fibroblast-derived factor which stimulates growth and morphogenesis of adjacent mammary tumor cells in vivo.

Animals↗
PubMed2005

PMT family of Candida albicans: five protein mannosyltransferase isoforms affect growth, morphogenesis and antifungal resistance.

Protein O-mannosyltransferases (Pmt proteins) initiate O-mannosylation of secretory proteins. The PMT gene family of the human fungal pathogen Candida albicans consists of PMT1 and PMT6, as well as three additional PMT genes encoding Pmt2, Pmt4 and Pmt5 isoforms described here. Both PMT2 alleles could not be deleted and growth of conditional strains, containing PMT2 controlled by the MET3- or tetOScHOP1-promoters, was blocked in non-permissive conditions, indicating that PMT2 is essential for growth. A homozygous pmt4 mutant was viable, but synthetic lethality of pmt4 was observed in combination with pmt1 mutations. Hyphal morphogenesis of a pmt4 mutant was defective under aerobic induction conditions, yet increased in embedded or hypoxic conditions, suggesting a role of Pmt4p-mediated O-glycosylation for environment-specific morphogenetic signalling. Although a PMT5 transcript was detected, a homozygous pmt5 mutant was phenotypically silent. All other pmt mutants showed variable degrees of supersensitivity to antifungals and to cell wall-destabilizing agents. Cell wall composition was markedly affected in pmt1 and pmt4 mutants, showing a significant decrease in wall mannoproteins. In a mouse model of haematogenously disseminated infection, PMT4 was required for full virulence of C. albicans. Functional analysis of the first complete PMT gene family in a fungal pathogen indicates that Pmt isoforms have variable and specific roles for in vitro and in vivo growth, morphogenesis and antifungal resistance.

Animals↗
PubMed1985

The role of transferrin receptors and iron delivery in mouse embryonic morphogenesis.

The iron-carrying serum protein transferrin is required for the proliferation and differentiation of embryonic tissues in culture. We studied the expression and role of transferrin receptors in two model systems using a monoclonal antibody against the transferrin receptor of mice. The addition of 20-100 micrograms/ml antibody to a chemically defined culture medium containing transferrin (10 micrograms/ml) inhibited morphogenesis and cell proliferation in kidneys and teeth. However, the antibody did not inhibit development when iron was delivered to the cells by a lipophilic iron chelator i.e., by-passing the receptor-mediated pathway. Hence, the binding of the receptor antibody to the receptor apparently did not affect cell proliferation, and the antibody was not toxic to the tissues. Our results suggest that the antibody to the transferrin receptor inhibits development by blocking the normal endocytotic route of iron delivery. Cells derived from embryonic kidneys and teeth expressed the transferrin receptor when cultured as monolayers. However, using immunofluorescent techniques, we were unable to detect the receptor in frozen tissue sections. It is possible that the seeding of cells in monolayer cultures affects the expression of the transferrin receptor, since it is known that all types of cells require transferrin for continued proliferation in culture. Organ-cultured kidney mesenchymal cells are not initially responsive to transferrin, but they acquire responsiveness as a consequence of an inductive tissue interaction. Although it remains unknown as to whether the acquisition of transferrin responsiveness is directly related to the expression of transferrin receptors, our results suggest that transferrin and its receptors play a role in embryonic morphogenesis.

Animals↗
PubMed1992

Morphogenesis and differentiation of Dictyostelium cells interacting with immobilized glucosides: dependence on DIF production.

Previous work has shown that multicellular morphogenesis of submerged Dictyostelium cells is inhibited when they bind to glucosides covalently linked to polyacrylamide gels. The amoebae aggregate normally, but then the aggregates repeatedly disperse and reaggregate, whereas control cells go on to form tight aggregates. We have investigated the role of the stalk cell differentiation inducing factors (DIFs) in this process. In the presence of cyclic AMP, amoebae submerged at high cell density accumulate DIF and differentiate into stalk cells. We find that stalk cell differentiation is inhibited by interaction of the cells with glucoside gels in these conditions, but can be restored by the addition of exogenous DIF-1. Since the responsiveness of cells to DIF-1 is not altered, it appears likely that the effect of the glucoside gel is to block DIF-1 production. Further, the addition of DIF-1 or DIF-2 stimulates the formation of tight aggregates by cells developing on glucoside gels in the absence of cyclic AMP, thus preventing the rounds of aggregation and disaggregation otherwise seen. This suggests a role for DIF in morphogenesis as well as in controlling cell differentiation. We propose a model in which immobilized glucosides activate a specific receptor ("food sensor") which drives the amoebae toward the vegetative state and inhibits DIF accumulation. DIF, on the other hand, induces tight aggregate formation and so locks the amoebae into the developmental program.

Animals↗
PubMed2006

Cell structure of developing downfeathers in the zebrafinch with emphasis on barb ridge morphogenesis.

The present ultrastructural and immunocytochemical study on the embryonic feathers of the zebrafinch, an altricial passerine bird, describes cellular differentiation of developing downfeathers. Barb ridges are folds of the original epidermis of the embryonic feather germ in which the basal-apical polarity of epidermal cells is upset. The result is the loss of most germinal activity of basal cells of the barb ridges so that only the embryonic epidermal layers remain. The more external layer is the primary periderm, followed by 4-6 layers of inner-periderm cells that mature into feather sheath and barb vane ridge cells. The following layer, the subperiderm, produces a small type of beta-keratin typical of feathers. In barb ridges, the subperiderm layer is displaced to form barbule plates and barb cells. The formation of branching barbules occurs by the presence of barb vane ridge cells that function as spacers between barbule cells. The fourth layer is homologous to the germinal layer of the epidermis, but in barb ridges it rapidly loses the germinal capability and becomes the cyclindrical layer of marginal plates. The study indicates that a necrotic process determines the carving out of the final feather shape, although apoptosis may also play a role. In fact, after barb and barbule cells have formed a keratinized syncitium, retraction of the vascular bed determines anoxia with the resultant necrosis of all feather cells. Only those of the keratinized syncitium remain to form the feather while supportive cells disappear. The sheath covering the barb and barbule syncitium is lost by the formation of a sloughing layer following degeneration of external barb ridge vane cells and loss of the sheath. It is proposed that the evolution of the morphogenetic process of barb ridge formation was peculiar to tubular outgrowths of the integument of archosaurian reptiles that evolved into birds. Once established in the embryonic programmes of skin morphogenesis of ancient birds, variations in the process of barb ridge morphogenesis allowed the fusion of ridges into large or branched ridges that originated the rachis. This process produced pennaceous feathers, among which were those later used for flight. The present study stresses that the morphogenetic process of barb ridge formation determines the concomitant appearance of barbs and barbules. As a consequence, intermediate forms of evolving feathers with only barbs but not barbules are unlikely or are derived from alteration of the above basic morphogenetic mechanism.

Animals↗
PubMed1998

The PS integrins are required for a regulatory event during Drosophila wing morphogenesis.

The PS1 and PS2 integrins are required for morphogenesis of the adult Drosophila wing. Clonal analysis experiments have shown that both integrins are necessary to maintain adhesion between the dorsal and ventral wing epithelia. We have found that early in wing morphogenesis, the integrins are also required for a regulatory event, and this may explain why PS1 and PS2 must be expressed on opposite surfaces of the wing at the onset of pupariation. Overexpression of integrin subunits during this early phase can lead to separation of dorsal and ventral surfaces, and we present evidence here that this dominant phenotype (the Blistermaker phenotype) results from a gain of integrin function, as opposed to negative interference from free integrin subunits. A possible model for an integrin signaling requirement in the wing is discussed.

Animals↗
PubMed1998

Extracellular matrix remodeling during morphogenesis.

The role of proteinases in extracellular matrix remodeling during the developmental program of bone, cartilage, muscle, and epithelial differentiation in the mandibular arch during embryogenesis was investigated. ECM changes accompany morphogenesis during development. The most dramatic changes occur during development of bone and cartilage. The expression of matrix metalloproteinases (MMPs) was altered by regulating expression of MMPs by growth factors, by inhibiting MMP activity, and by genetic ablation of MMPs. The data point to critical roles for MMPs in cartilage development and endochondral bone formation. MMPs appear to regulate not only ECM degradation but also programmed cell death, cell migration, and invasion during these morphogenic processes. The data suggest that matrix metalloproteinases play a pivotal role in the morphogenesis of structures derived from epithelium (oral sulcus), somitic mesoderm (tongue), and cranial neural crest (Meckel's cartilage).

Animals↗
PubMed2005

MicroRNAs regulate brain morphogenesis in zebrafish.

MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally. To block all miRNA formation in zebrafish, we generated maternal-zygotic dicer (MZdicer) mutants that disrupt the Dicer ribonuclease III and double-stranded RNA-binding domains. Mutant embryos do not process precursor miRNAs into mature miRNAs, but injection of preprocessed miRNAs restores gene silencing, indicating that the disrupted domains are dispensable for later steps in silencing. MZdicer mutants undergo axis formation and differentiate multiple cell types but display abnormal morphogenesis during gastrulation, brain formation, somitogenesis, and heart development. Injection of miR-430 miRNAs rescues the brain defects in MZdicer mutants, revealing essential roles for miRNAs during morphogenesis.

Animals↗