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At least 883 records · Page 49Linked to original sources
PubMed2001

Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud.

Endostatin (ES) inhibits endothelial cell migration and has been found to bind to glypicans (Gpcs) on both endothelial cells and renal epithelial cells. We examined the possibility that ES might regulate epithelial cell morphogenesis. The addition of ES to cultured epithelial cells causes an inhibition of both hepatocyte growth factor- and epidermal growth factor-dependent process formation and migration. In contrast, ES does not inhibit epidermal growth factor-dependent morphogenesis in renal epithelial cells derived from Gpc-3 -/mice, whereas expression of Gpc-1 in these cells reconstitutes ES responsiveness. Gpc-3 -/mice have been shown to display enhanced ureteric bud (UB) branching early in development, and cultured UB cells release ES into the media, suggesting that ES binding to Gpcs may regulate UB branching. The addition of ES inhibits branching of the explanted UB, whereas a neutralizing Ab to ES enhances UB outgrowth and branching. Thus, local expression of ES at the tips of the UB may play a role in the regulation of UB arborization.

Animals↗
PubMed1970

Effects of cytochalasin B upon microfilaments involved in morphogenesis of salivary epithelium.

Cytochalasin B causes cultured mouse salivary gland epithelium to lose its characteristic shape and to cease undergoing morphogenesis. The drug causes disorganization of the 50 A microfilaments in epithelial cells that are thought to control cell shape because of contractile properties. Upon removal of cytochalasin, epithelia regain normal shape and resume morphogenesis. Exceptionally large bundles of microfilaments appear in such recovered epithelial cells at points where their contractile activity could account for the changes in cell and tissue shape.

Animals↗
PubMed1989

Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1.

The effects on human immunodeficiency virus type 1 virion morphogenesis and on virus replication of mutations that affect posttranslational processing of the capsid precursor protein are described. A change in the glycine residue at position two from the N terminus abolishes the myristoylation of the precursor proteins and also prevents virus particle release. Mutations in the viral protease gene abolish proteolytic cleavage of the capsid precursor but do not prevent the formation and budding of virion particles of immature appearance. Mutations that alter the sequence of the sites normally used for cleavage of the major capsid protein p24 from the capsid precursor alter virion morphogenesis and prevent virus replication.

Animals↗
PubMed1995

Bombesin and [Leu8]phyllolitorin promote fetal mouse lung branching morphogenesis via a receptor-mediated mechanism.

Pulmonary neuroendocrine cells are localized predominantly at airway branchpoints. Previous work showed that gastrin-releasing peptide (GRP), a major pulmonary bombesin-like peptide, occurred in neuroendocrine cells exclusively in branching human fetal airways. We now demonstrate that GRP and GRP receptor genes are expressed in fetal mouse lung as early as embryonic day 12 (E12), when lung buds are beginning to branch. By in situ hybridization, GRP receptor transcripts were at highest levels in mesenchymal cells at cleft regions of branching airways and blood vessels. To explore the possibility that bombesin-like peptides might play a role in branching morphogenesis, E12 lung buds were cultured for 48 hr in serum-free medium. In the presence of 0.10-10 microM bombesin, branching was significantly augmented as compared with control cultures, with a peak of 94% above control values at 1 microM (P < 0.005). The bombesin receptor antagonist [Leu13- psi(CH2NH)Leu14]bombesin alone (100 nM) had no effect on baseline branching but completely abolished bombesin-induced branching. A bombesin-related peptide, [Leu8]phyllolitorin also increased branching (65% above control values at 10 nM, P < 0.005). [Leu8]Phyllolitorin also significantly augmented thymidine incorporation in cultured lung buds. Fibronectin, which is abundant at branchpoints, induces GRP gene expression in undifferentiated cell lines. These observations suggest that BLPs secreted by pulmonary neuroendocrine cells may contribute to lung branching morphogenesis. Furthermore, components of branchpoints may induce pulmonary neuroendocrine cell differentiation as part of a positive feedback loop, which could account in part for the high prevalence of these cells at branchpoints.

Animals↗
PubMed1997

Essential role of a kinesin-like protein in Arabidopsis trichome morphogenesis.

Little is known about how cell shape is controlled. We are using the morphogenesis of trichomes (plant hairs) on the plant Arabidopsis thaliana as a model to study how cell shape is controlled. Wild-type Arabidopsis trichomes are large, single epidermal cells with a stalk and three or four branches, whereas in zwichel (zwi) mutants the trichomes have a shortened stalk and only two branches. To further understand the role of the ZWI gene in trichome morphogenesis we have cloned the wild-type ZWICHEL (ZWI) gene by T-DNA tagging, and report here that it encodes a member of the kinesin superfamily of microtubule motor proteins. Kinesin proteins transport diverse cellular materials in a directional manner along microtubules. Kinesin-like proteins are characterized by a highly conserved "head" region that comprises the motor domain, and a nonconserved "tail" region that is thought to participate in recognition and binding of the appropriate cargo.

Acanthamoeba↗
PubMed1997

Analysis of the role of the Spitzenkörper in fungal morphogenesis by computer simulation of apical branching in Aspergillus niger.

High-resolution video microscopy, image analysis, and computer simulation were used to study the role of the Spitzenkörper (Spk) in apical branching of ramosa-1, a temperature-sensitive mutant of Aspergillus niger. A shift to the restrictive temperature led to a cytoplasmic contraction that destabilized the Spk, causing its disappearance. After a short transition period, new Spk appeared where the two incipient apical branches emerged. Changes in cell shape, growth rate, and Spk position were recorded and transferred to the FUNGUS SIMULATOR program to test the hypothesis that the Spk functions as a vesicle supply center (VSC). The simulation faithfully duplicated the elongation of the main hypha and the two apical branches. Elongating hyphae exhibited the growth pattern described by the hyphoid equation. During the transition phase, when no Spk was visible, the growth pattern was nonhyphoid, with consecutive periods of isometric and asymmetric expansion; the apex became enlarged and blunt before the apical branches emerged. Video microscopy images suggested that the branch Spk were formed anew by gradual condensation of vesicle clouds. Simulation exercises where the VSC was split into two new VSCs failed to produce realistic shapes, thus supporting the notion that the branch Spk did not originate by division of the original Spk. The best computer simulation of apical branching morphogenesis included simulations of the ontogeny of branch Spk via condensation of vesicle clouds. This study supports the hypothesis that the Spk plays a major role in hyphal morphogenesis by operating as a VSC-i.e., by regulating the traffic of wall-building vesicles in the manner predicted by the hyphoid model.

Aspergillus niger↗
PubMed1995

Inhibition of capillary morphogenesis and associated apoptosis by dominant negative mutant transforming growth factor-beta receptors.

Transforming growth factor-beta 1 (TGF-beta 1) induces angiogenesis in vivo and capillary morphogenesis in vitro. Two receptor serine/threonine kinases (types I and II) have been identified as signal transducing TGF-beta receptors. We explored the possibility of inhibiting TGF-beta-mediated events in glomerular capillary endothelial cells using a TGF-beta type II receptor (T beta R-II) transdominant negative mutant. A mutant TGF-beta type II receptor (T beta R-IIM), lacking the cytoplasmic serine/threonine kinase domain, was produced by polymerase chain reaction using rat T beta R-II cDNA as template. Since T beta R-II and TGF-beta type I receptor (T beta R-I) heterodimerize for signal transduction, the mutant receptor competes for binding to wild-type T beta R-I, hence acting in a dominant negative fashion. Glomerular capillary endothelial cells were stably transfected with T beta R-IIM, and four independent clones were expanded. That the T beta R-IIM mRNA was expressed was shown by reverse transcriptase-polymerase chain reaction, RNase protection assay, and Northern analysis. Presence of cell surface T beta R-IIM protein was shown by affinity cross-linking with 125I-TGF-beta 1. In wild-type endothelial cells, TGF-beta 1 (2 ng/ml) significantly inhibited [3H]thymidine incorporation to 63 +/- 10% of control (n = 4). In transfected endothelial cells carrying T beta R-IIM, TGF-beta 1 stimulated [3H]thymidine incorporation to 131 +/- 9% of control (n = 4, p < 0.005). Also, in wild-type endothelial cells, endogenous and exogenous TGF-beta 1 induced apoptosis and associated capillary formation. Both apoptosis and capillary formation were uniformly and entirely absent in transfected endothelial cells carrying T beta R-IIM. This represents the first demonstration that capillary morphogenesis in vitro is associated with apoptosis, and that interference with T beta R-II signaling inhibits this process in glomerular capillary endothelial cells.

Animals↗
PubMed1999

A conserved inositol phospholipid binding site within the pleckstrin homology domain of the Gab1 docking protein is required for epithelial morphogenesis.

Stimulation of the hepatocyte growth factor receptor tyrosine kinase, Met, induces the inherent morphogenic program of epithelial cells. The multisubstrate binding protein Gab1 (Grb2-associated binder-1) is the major phosphorylated protein in epithelial cells following activation of Met. Gab1 contains a pleckstrin homology domain and multiple tyrosine residues that act to couple Met with multiple signaling proteins. Met receptor mutants that are impaired in their association with Gab1 fail to induce a morphogenic program in epithelial cells, which is rescued by overexpression of Gab1. The Gab1 pleckstrin homology domain binds to phosphatidylinositol 3,4, 5-trisphosphate and contains conserved residues, shown from studies of other pleckstrin homology domains to be crucial for phospholipid binding. Mutation of conserved phospholipid binding residues tryptophan 26 and arginine 29, generates Gab1 proteins with decreased phosphatidylinositol 3,4,5-trisphosphate binding, decreased localization at sites of cell-cell contact, and reduced ability to rescue Met-dependent morphogenesis. We conclude that the ability of the Gab1 pleckstrin homology domain to bind phosphatidylinositol 3,4,5-trisphosphate is critical for subcellular localization of Gab1 and for efficient morphogenesis downstream from the Met receptor.

Amino Acid Sequence↗
PubMed2000

Phosphorylation of c-Crk II on the negative regulatory Tyr222 mediates nerve growth factor-induced cell spreading and morphogenesis.

The Crk family of adaptor proteins participate in diverse signaling pathways that regulate growth factor-induced proliferation, anchorage-dependent DNA synthesis, and cytoskeletal reorganization, important for cell adhesion and motility. Using kidney epithelial 293T cells for transient co-transfection studies and the nerve growth factor (NGF)-responsive PC12 cell line as a model system for neuronal morphogenesis, we demonstrate that the non-receptor tyrosine kinase c-Abl is an intermediary for NGF-inducible c-Crk II phosphorylation on the negative regulatory Tyr(222). Transient expression of a c-Crk II Tyr(222) point mutant (c-Crk Y222F) in 293T cells induces hyperphosphorylation of paxillin on Tyr(31) and enhances complex formation between c-Crk Y222F and paxillin as well as c-Crk Y222F and c-Abl, suggesting that c-Crk II Tyr(222) phosphorylation induces both the dissociation of the Crk SH2 domain from paxillin and the Crk SH3 domain from c-Abl. Interestingly, examination of the early kinetics of NGF stimulation in PC12 cells showed that c-Crk II Tyr(222) phosphorylation preceded paxillin Tyr(31) phosphorylation, followed by a transient initial dissociation of the c-Crk II paxillin complex. PC12 cells overexpressing c-Crk Y222F manifested a defect in cellular adhesion and neuritogenesis that led to detachment of cells from the extracellular matrix, thus demonstrating the biological significance of c-Crk II tyrosine phosphorylation in NGF-dependent morphogenesis. Whereas previous studies have shown that Crk SH2 binding to paxillin is critical for cell adhesion and migration, our data show that the phosphorylation cycle of c-Crk II determines its dynamic interaction with paxillin, thereby regulating turnover of multiprotein complexes, a critical aspect of cytoskeletal plasticity and actin dynamics.

Animals↗
PubMed1997

Expression of FGF-1 and FGF-2 mRNA during lens morphogenesis, differentiation and growth.

PURPOSE: There is now considerable evidence that FGF is involved in lens differentiation and growth throughout life. The aim of this study was to determine potential sites of FGF production in and near the lens during morphogenesis, differentiation and growth. METHODS: The distribution of FGF-1 and FGF-2 mRNAs was analysed in embryonic, weanling and adult rat eyes by in situ hybridization. RESULTS: During lens morphogenesis, there was distinct expression of FGF-1, but not FGF-2, in the lens placode and retinal disc cells. Subsequently, both forms of FGF showed similar expression patterns. During lens differentiation, distinct expression of FGFs was associated with elongating primary fiber cells. From embryonic day 20 onwards, lenses showed strongest expression of FGF mRNAs in the transitional zone, where epithelial cells differentiate into fibers, with weaker expression in the anterior epithelium. Messenger RNAs for both FGFs were also localised in ocular tissues near the lens and bordering the ocular media, particularly the cornea, ciliary body, iris and neural retina. CONCLUSIONS: These findings are consistent with the known distribution of FGF protein in the eye and implicate various ocular tissues as potential sources of FGF that may influence lens cells. Furthermore, the fact that lens cells have the potential for synthesizing FGF, together with evidence from previous studies that lens cells express FGF receptors and respond to lens-derived FGF, raises the possibility that some aspects of lens cell behaviour in situ may be influenced by autocrine mechanism(s) of FGF stimulation.

Animals↗
PubMed2005

Hsp27 expression coincides with epidermal stratification during human epidermal morphogenesis.

Heat shock protein 27 (Hsp27), apart from its protective function in response to stress, is implicated in the regulation of cell growth, differentiation and apoptosis. Data on the expression of Hsp27 in the developing human epidermis are sparse and partially conflicting. Thus, the purpose of the present study was to investigate Hsp27 expression during the morphogenesis of human epidermis. Skin biopsies and dispase-separated epidermal sheets obtained from 7 human embryos (7 and 8 weeks estimated gestational age, EGA), from 79 human fetuses (9-23 weeks EGA) and from 10 healthy adult volunteers were investigated by immunohistochemistry and Western blotting, respectively. The earliest detection of Hsp27 expression was found by immunohistochemistry at the 12th week EGA (basal and intermediate layer) and by Western blotting at the 9th week EGA. From the 16th to the 23rd week EGA immunoreactivity was not detectable in the basal layer, whereas in the overlying layers it revealed a differentiation-related pattern. The simultaneous onset of epidermal stratification and Hsp27 expression (9th week EGA) and the alterations of the latter in the subsequent stages of development, suggest that this stress protein may be involved in the molecular events underlying human epidermal morphogenesis.

Adult↗
PubMed2003

A Geometro-mechanical model for pulsatile morphogenesis.

A model is proposed which imitates the morphogenesis of several species of the lower invertebrate animals, the hydroid polyps and permits the derivation of the geometry (surface curvature) of each developmental stage from that of the preceding stage. The model is based upon two experimentally verified assumptions. First, neighbouring cells are assumed to compress each other laterally in a regular and species-specific pulsatile manner. It is this pressure, and/or an active cell reaction to it, which changes the curvature of a cell layer. Secondly, cell layers are assumed to have quasi-elastic properties tending to smooth out their curvature. With our model, the different pulsatile patterns of cell-cell pressure are reproduced and the elasticity parameters are modulated. As a result, within a large zone of parameter values (a so-called "morphogenetic zone", MZ) realistic shapes of the rudiments are reproduced. The main principles of the model can also be used for interpreting the morphogenesis of other groups of animals. A suggested model emphasizes the self-organizing properties of a "stressed geometry" of embryonic rudiments.

Cell Size↗
PubMed2005

The role of matrix metalloproteinases in the morphogenesis of the cerebellar cortex.

The morphogenesis of the cerebellar cortex depends on intrinsic genetic programs as well as orchestrated cell-cell/cell-extracellular matrix (ECM) interactions. The matrix metalloproteinase (MMP) family comprises of more than 20 members that catalyze the degradation of all the protein constituents of the ECM. These proteolytic endopeptidases mediate cell-cell/cell-ECM interactions by remodeling the ECM and modulating the activity of membrane-associated receptors. The activity of MMPs is negatively controlled by the tissue inhibitors of metalloproteinases (TIMPs). The MMPs and TIMPs regulate diverse neuronal functions including migration, process extension and synaptic plasticity. MMP-2, -3, -9, membrane type 5-MMP (MT5-MMP), TIMP-1, -2 and -3 are expressed in the developing cerebellum. The spatiotemporal pattern of expression/activity of these enzymes suggests that they play a role in the development of the cerebellar cortex. Blockage of MMP-2/-9 activity by specific inhibitors or blocking antibody, as well as using MMP-9 knock-out mice, clearly establishes that MMP-2/-9 participates in the regulation of morphogenesis of the cerebellum. The potential contributions of these enzymes to granule neuron migration, Purkinje cell dendritogenesis and synaptogenesis are discussed.

Animals↗
PubMed1985

Expression of cell-adhesion molecules in embryonic induction. II. Morphogenesis of adult feathers.

The developmental appearance of cell-adhesion molecules (CAMs) was mapped during the morphogenesis of the adult chicken feather. Neural CAM (N-CAM), liver CAM (L-CAM), and neuron-glia CAM (Ng-CAM), as well as substrate molecules (laminin and fibronectin), were compared in newborn chicken skin by immunohistochemical means. N-CAM was found to be enriched in the dermal papilla, which was closely apposed to L-CAM-positive papillar ectoderm. The two CAMs were then co-expressed in cells of the collar epithelium. Subsequently generated barb epithelia expressed only L-CAM, but N-CAM reappeared periodically on cells between developing barbs and barbules. N-CAM first appeared on a single L-CAM-positive basilar cell located in each valley flanked by two adjacent barb ridges. Subsequently, the expression of N-CAM extended one cell after another to include the whole basilar layer. N-CAM also appeared in the L-CAM-positive axial-plate epithelia, beginning in a single cell located at the ridge base. The two collectives of N-CAM-positive epithelia constituting the marginal and axial plates then disintegrated, leaving interdigitating spaces between keratinized structures that had previously expressed L-CAM. The morphological transformation from an epithelial cylinder to a three-level branched feather pattern is thus achieved by coupling alternating CAM expression in linked cell collectives with specific differentiation events, such as keratinization. During all of these morphogenetic processes, laminin and fibronectin formed a continuous basement membrane separating pulp from feather epithelia, and were excluded from the sites involved in periodic appearances of N-CAM. The same staining pattern described for developing chickens persisted in the feather follicles of adult chicken tissue that have gone through several cycles of molting. Cyclic expression of the two different CAMs underlies each of the different morphological events that are generated epigenetically during feather morphogenesis.

Age Factors↗
PubMed1986

Coupled expression and colocalization of 140K cell adhesion molecules, fibronectin, and laminin during morphogenesis and cytodifferentiation of chick lung cells.

We have analyzed the expression and distribution of fibronectin, laminin, and the 140K cell adhesion molecules (140K complex) in embryonic chick lung cells by a combination of biochemical and immunofluorescent approaches. The 140K complex was identified by monoclonal antibody JG22E as a complex of glycoproteins averaging 140,000 Mr and has been implicated in vitro as a receptor for fibronectin and laminin. Our studies provide the first description that the 140K complex is developmentally regulated, and that the 140K complex appears to be involved in adhesion of epithelial and endothelial cells during morphogenesis. We have shown that the 140K complex is expressed in high quantity in embryonic lung cell types, but is markedly reduced in all of the differentiated cell types except smooth muscle. Embryonic lung cells are enriched in 140K complex on portions of cells in close proximity to areas rich in fibronectin. For example, during the formation of airways and alveolar tissues, 140K complex is concentrated at the basal surfaces of epithelial cells adjacent to fibronectin. Likewise, during the angiogenic invasion of capillaries into lung mesenchyme, the 140K complex becomes localized at sites on the basal surfaces of endothelial cells in close contact with fibronectin. Finally, cytodifferentiating lung smooth muscle cells show unusually high levels of 140K complex, fibronectin, and laminin that persist into the adult. In contrast to fibronectin, laminin is found to be uniformly distributed in the basement membranes of differentiating epithelial cells. It becomes prominent in adult alveolar epithelium and airway epithelium concomitant with a reduction or loss of 140K complex and fibronectin at cell-basement membrane attachment sites. Surprisingly, laminin is also present in a punctate pattern in the mesenchyme of early lung buds, however, laminin, fibronectin, and 140K complex are greatly reduced or lost during mesenchymal maturation. Our results are consistent with the active participation of the 140K complex in cell-to-matrix adhesion during morphogenesis of alveolar walls and cytodifferentiation of mesenchymal and smooth muscle cells.

Animals↗
PubMed1994

Targeted expression of stromelysin-1 in mammary gland provides evidence for a role of proteinases in branching morphogenesis and the requirement for an intact basement membrane for tissue-specific gene expression.

The extracellular matrix (ECM) is an important regulator of the differentiated phenotype of mammary epithelial cells in culture. Despite the fact that ECM-degrading enzymes have been implicated in morphogenesis and tissue remodeling, there is little evidence for a direct role for such regulation in vivo. We generated transgenic mice that express autoactivated isoforms of the matrix metalloproteinase stromelysin-1, under the control of the whey acidic protein gene promoter, to examine the effect of inappropriate expression of this enzyme. Stromelysin-1 is implicated as the primary player in the loss of basement membrane and loss of function in the mammary gland during involution. The transgene was expressed at low levels in mammary glands of virgin female mice, leading to an unexpected phenotype: The primary ducts had supernumerary branches and showed precocious development of alveoli that expressed beta-casein at levels similar to that of an early- to mid-pregnant gland. Lactating glands showed high levels of transgene expression, with accumulation at the basement membrane, and a decrease in laminin and collagen IV, resulting in a loss of basement membrane integrity; this was accompanied by a dramatic alteration of alveolar morphology, with decreased size and shrunken lumina containing little beta-casein. During pregnancy, expression of endogenous whey acidic protein and beta-casein was reduced in transgenic glands, confirming the observed dependence of milk protein transcription of ECM in mammary epithelial cells in culture. These data provide direct evidence that stromelysin-1 activity can be morphogenic for mammary epithelial cells, inducing hyperproliferation and differentiation in virgin animals, and that its lytic activity can, indeed, disrupt membrane integrity and reduce mammary-specific function. We conclude that the balance of ECM-degrading enzymes with their inhibitors, and the associated regulation of ECM structure, is crucial for tissue-specific gene expression and morphogenesis in vivo.

Animals↗
PubMed1994

Thyroxine is the serum factor that regulates morphogenesis of columnar cartilage from isolated chondrocytes in chemically defined medium.

Epiphyseal chondrocytes cultured in a medium containing 10% serum may be maintained as three dimensional aggregates and differentiate terminally into hypertrophic cells. There is an attendant expression of genes encoding type X collagen and high levels of alkaline phosphatase activity. Manipulation of the serum concentration to optimal levels of 0.1 or 0.01% in this chondrocyte pellet culture system results in formation of features of developing cartilage architecture which have been observed exclusively in growth cartilage in vivo. Cells are arranged in columns radiating out from the center of the tissue, and can be divided into distinct zones corresponding to the recognized stages of chondrocyte differentiation. Elimination of the optimal serum concentration in a chemically defined medium containing insulin eliminates the events of terminal differentiation of defined cartilage architecture. Chondrocytes continue to enlarge into hypertrophic cells and synthesize type X collagen mRNA and protein, but in the absence of the optimal serum concentration, alkaline phosphatase activity does not increase and the cells retain a random orientation. Addition of thyroxine to the chemically defined medium containing insulin and growth hormone results in dose-dependent increases in both type X collagen synthesis and alkaline phosphatase activity, and reproduces the optimal serum-induced morphogenesis of chondrocytes into a columnar pattern. These experiments demonstrate the critical role of thyroxine in cartilage morphogenesis.

Animals↗
PubMed1994

The mouse ileal lipid-binding protein gene: a model for studying axial patterning during gut morphogenesis.

Normal, chimeric-transgenic, and transgenic mice have been used to study the axial patterns of ileal lipid-binding protein gene (Ilbp) expression during and after completion of gut morphogenesis. Ilbp is initially activated in enterocytes in bidirectional wave that expands proximally in the ileum and distally to the colon during late gestation and the first postnatal week. This activation occurs at the same time that a wave of cytodifferentiation of the gut endoderm is completing its unidirectional journey from duodenum to colon. The subsequent contraction of Ilbp's expression domain, followed by its reexpansion from the distal to proximal ileum, coincides with a critical period in gut morphogenesis (postnatal days 7-28) when its proliferative units (crypts) form, establish their final stem cell hierarchy, and then multiply through fission. The wave of reactivation is characterized by changing patterns of Ilbp expression: (a) at the proximal most boundary of the wave, villi contain a mixed population of scattered ileal lipid-binding protein (ILBP)-positive and ILBP-negative enterocytes derived from the same monoclonal crypt; (b) somewhat more distally, villi contain vertical coherent stripes of wholly ILBP-positive enterocytes derived from monoclonal crypts and adjacent, wholly ILBP-negative stripes of enterocytes emanating from other monoclonal crypts; and (c) more distally, all the enterocytes on a villus support Ilbp expression. Functional mapping studies of Ilbp's promoter in transgenic mice indicate that nucleotides -145 to +48 contain cis-acting elements sufficient to produce an appropriately directed distal-to-proximal wave of Ilbp activation in the ileum, to maintain an appropriate axial distribution of monophenotypic wholly reporter-positive villi in the distal portion of the ileum, as well as striped and speckled villi in the proximal portion of its expression domain, and to correctly support reporter production in villus-associated ileal enterocytes. Nucleotides -417 to -146 of Ilbp contain a "temporal" suppressor that delays initial ileal activation of the gene until the second postnatal week. Nucleotides -913 to -418 contain a temporal suppressor that further delays initial activation of the gene until the third to fourth postnatal week, a spatial suppressor that prohibits gene expression in the proximal quarter of the ileum and in the proximal colon, and a cell lineage suppressor that prohibits expression in goblet cells during the first two postnatal weeks.

Amino Acid Sequence↗