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PubMed2006

Extracellular matrix of ovarian tumors.

Tumor cells interfere with the normal programming of extracellular matrix (ECM) biosynthesis and can extensively modify the structure and composition of the matrix. The role of ECM components is becoming increasingly recognized as an important determinant for the growth and progression of solid tumors. The extensive remodeling of the normal ECM in tumors can proceed through the degradation of pre-existing ECM molecules and/or by the neosynthesis of ECM components, which in many cases are not present in the ECM of normal tissues. In the ovary the ECM comprises a variety of molecules including the collagen superfamily and noncollagenous proteins such as glycoproteins, proteoglycans, and hyaluronan. Elevated levels of laminin-gamma2, collagen types I and III, fibronectin, syndecan-1, glypican-1, versican, and hyaluronan and its receptors CD44 have all been associated with a poor prognosis of ovarian cancers. Generally, there is a differential expression of laminin chains alpha1, alpha4, and beta2 among serous (alpha1, beta2), mucinous (alpha4), and endometrioid (alpha1) tumors. This review focuses on these and other ECM molecules in ovarian tumors.

Extracellular Matrix↗

PubMed2001

The role of extracellular matrix in transperitoneal transport of water and solutes.

OBJECTIVE: To define the extracellular matrix (ECM), to discuss the physical properties of its components and their impact on transport, and to review data in humans and in animals on the importance of hyaluronan to peritoneal dialysis. METHODS: Literature survey. RESULTS: The ECM fills the interstitium between parenchymal cells and blood vessels in the subperitoneal interstitium. It is responsible for the interstitial resistance to solute and water transfer through the peritoneal barrier. Major components are collagen and hyaluronan, which are synthesized locally in the peritoneal tissue. Synthesis and deposition of these components increase with inflammation, and concentrations of the components influence the mechanical properties of the tissue and the interstitial Starling forces as well as transport. Removal of hyaluronan appears to increase the rates of water and large-solute transport. Addition of hyaluronan to dialysate appears to enhance fluid recovery and to reduce protein loss. CONCLUSION: Many of the physicochemical properties of ECM components are well described, but a large knowledge gap remains concerning the in vivo consequences of specific alterations in the interstitial components. More research is needed.

Animals↗

PubMed1994

Regulation of prostate-specific antigen gene expression in LNCaP human prostatic carcinoma cells by growth, dihydrotestosterone, and extracellular matrix.

We have examined the role of extracellular matrix (ECM), cell growth, and dihydrotestosterone on the expression of prostate-specific antigen (PSA) by human prostatic carcinoma cells LNCaP. ECM induced a transient decrease in PSA mRNA even in the presence of growth factors. PSA mRNA, but not actin mRNA, was down-regulated on ECM in a biphasic manner and was not detected up to 48 hr after culture, but was re-expressed after 3 days. Cycloheximide and actinomycin D pretreatment did not prevent ECM-induced down-regulation of PSA mRNA, while actinomycin D-treated cells on plastic maintained stable PSA mRNA levels. DNA synthesis and PSA glycoprotein secretion were also transiently suppressed on ECM. LNCaP growth inhibition correlated with decreased glyceraldehyde phosphate dehydrogenase mRNA levels. However, the transient growth suppression induced by ECM was not observed with primary endothelial cells on Matrigel. Down-regulation of PSA mRNA by culture on Matrigel was reversible upon transfer to a different matrix substrate. Re-expression was highest on heparan sulfate proteoglycan (4-fold) and fibronectin or collagen I (2-fold) compared to plastic or laminin. Our results indicate that the morphology and proliferation of LNCaP cells may be regulated by the ability of ECM to control cellular differentiation and proliferation.

Adenocarcinoma↗

PubMed2005

Cyclodextrin polysulphates repress IL-1 and promote the accumulation of chondrocyte extracellular matrix.

OBJECTIVE: To evaluate the influence of cyclodextrin polysulphate (CDPS) on the extracellular matrix (ECM) metabolism of human articular cartilage chondrocytes. METHODS: Isolated chondrocytes from femoral condyle cartilage of human knee joints were cultured in gelled alginate to maintain their differentiated phenotype. During 1 week of culture, the cells were exposed to different concentrations of CDPS. Synthesis of aggrecans was investigated in these cultures after using Na(2)(35)SO(4) as a radioactive precursor during the last 24h of culture. The artificial matrix was then solubilised with Na-citrate and newly synthesised aggrecan aggregates, accumulated during culture, were liberated and assayed. The isolated chondrocytes were labelled with antibodies against aggrecan and type II collagen to analyse the ECM molecules in the cell-associated matrix (CAM). Plasma membrane levels of receptors for insulin-like growth factor-1 (IGF-1RI) and for interleukin-1 (IL-1RI and IL-1RII), as well as levels of IGF-1, IL-1alpha and -beta were determined after the cells had been permeabilized and stained with the appropriate antibodies. The release of IL-6 in the culture media was used as a variable reflecting auto/paracrine IL-1 activity of the cells in different experimental conditions. RESULTS: CDPS significantly increased total (35)S-incorporation rates in ECM aggrecan. When compared with controls, CDPS-treated chondrocytes expressed significantly higher CAM aggrecan and type II collagen levels. As plasma membrane-bound IGFR1 and intracellular IGF-1 levels remained unchanged, this increase in accumulated CAM compounds may have resulted from suppressed catabolic activities by the chondrocytes in culture. CDPS-treated cells expressed significantly lower amounts of intracellular IL-1alpha and -beta levels. Plasma membrane-bound IL-1RI and decoy IL-1RII remained unchanged. beta-cyclodextrin-treated chondrocytes released significantly less IL-6 in the supernatant culture media. CONCLUSION: CDPS is a novel polysulfated polysaccharide showing cartilage structure modifying effects in vitro as it improves the synthesis of aggrecan and the accumulation of CAM macromolecules. This effect probably resulted in part from the downregulation of IL-1.

Aggrecans↗

PubMed1990

Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix.

The relationship of cell proliferation to the temporal expression of genes characterizing a developmental sequence associated with bone cell differentiation was examined in primary diploid cultures of fetal calvarial derived osteoblasts by the combined use of autoradiography, histochemistry, biochemistry, and mRNA assays of osteoblast cell growth and phenotypic genes. Modifications in gene expression define a developmental sequence that has 1) three principle periods--proliferation, extracellular matrix maturation, and mineralization--and 2) two restriction points to which the cells can progress but cannot pass without further signals--the first when proliferation is down-regulated and gene expression associated with extracellular matrix maturation is induced, and the second when mineralization occurs. Initially, actively proliferating cells, expressing cell cycle- and cell growth-regulated genes, produce a fibronectin/type I collagen extracellular matrix. A reciprocal and functionally coupled relationship between the decline in proliferative activity and the subsequent induction of genes associated with matrix maturation and mineralization is supported by 1) a temporal sequence of events in which there is an enhanced expression of alkaline phosphatase immediately following the proliferative period, and later, an increased expression of osteocalcin and osteopontin at the onset of mineralization; 2) increased expression of a specific subset of osteoblast phenotype markers, alkaline phosphatase and osteopontin, when proliferation is inhibited by hydroxyurea; and 3) enhanced levels of expression of the osteoblast markers as a function of ascorbic acid-induced collagen deposition, suggesting that the extracellular matrix contributes to both the shutdown of proliferation and the development of the osteoblast phenotype.

Alkaline Phosphatase↗

PubMed2000

Lecticans: organizers of the brain extracellular matrix.

Lecticans are a family of chondroitin sulfate proteoglycans, encompassing aggrecan, versican, neurocan and brevican. These proteoglycans are characterized by the presence of a hyaluronan-binding domain and a C-type lectin domain in their core proteins. Through these domains, lecticans interact with carbohydrate and protein ligands in the extracellular matrix and act as linkers of these extracellular matrix molecules. In adult brain, lecticans are thought to interact with hyaluronan and tenascin-R to form a ternary complex. We propose that the hyaluronan-lectican-tenascin-R complex constitutes the core assembly of the adult brain extracellular matrix, which is found mainly in pericellular spaces of neurons as 'perineuronal nets'.

Alternative Splicing↗

PubMed1983

Histochemical analysis of extracellular matrix material in embryonic mouse lens morphogenesis.

Extracellular matrix material (ECM) present during mouse lens morphogenesis was studied histologically by the periodic acid-Schiff, Alcian blue 8GX, pH 2.5, high iron diamine, and Van Gieson methods, and enzymatically with bovine testicular hyaluronidase, Streptomyces hyaluronidase, malt diastase, and collagenase. The basal lamina of the optic vesicle prior to lens placode formation was found to be higher in glycosaminoglycan (GAG) content than was the ectodermal basal lamina. Upon apposition of the optic vesicle and presumptive lens ectoderm, the ECM plus basal laminae appeared as the equivalent of adding both optic vesicle-associated and ectodermal-associated basal lamina. The proposal is made that the initial triggering mechanism of lens morphogenesis consists of a cross-linking and polymerization of optic vesicle-associated GAG to ectodermal-associated glycoproteins resulting in a firm attachment between the structures. Basal lamina associated with the presumptive pigmented retina and also the more ventral part of the interface matrix were found to change from predominantly GAG in early stages to collagen deposits in more advanced stages, temporally coinciding with the appearance of differentiative markers in each structure. This pattern of GAG turnover and replacement by collagen during the course of development is also seen in mouse salivary gland morphogenesis (M. R. Bernfield, S. D. Banerjee, and R. H. Cohn (1972). J. Cell Biol. 52, 674-686.).

Animals↗

PubMed1998

Acute and long-lasting changes in extracellular-matrix chondroitin-sulphate proteoglycans induced by injection of chondroitinase ABC in the adult rat brain.

Lattice-like perineuronal accumulations of extracellular-matrix proteoglycans have been shown to develop during postnatal maturation and to persist throughout life as perineuronal nets (PNs) in many brain regions. However, the dynamics of their reorganization in adults are as yet unknown. The aim of the present study was to examine the capability of PNs for reconstitution after experimental destruction and to search for possible consequences of extracellular-matrix degradation for neurons and glial cells. The changes were induced by single intracortical injections of Proteus vulgaris chondroitinase ABC and studied after postinjection periods of 1 day to 5 months. The N-acetylgalactosamine-binding Wisteria floribunda agglutinin (WFA), an antibody against chondroitin-sulphate proteoglycans, three antibodies recognizing initial chondroitin or chondroitin-sulphate moieties ('stubs') of proteoglycan core proteins, an antibody against the hyaluronan-binding protein component of versican, and biotinylated hyaluronectin, which binds to hyaluronan, were used as cytochemical markers. One day postinjection, the WFA-binding sites and hyaluronan were shown to be almost completely removed within a circumscribed digestion zone. The staining of different core-protein components revealed only fragments of PNs. These changes were found to be partly compensated 4 weeks after injection of chondroitinase ABC. After 8 and 12 weeks postinjection, the cytochemical and structural characteristics as well as the area-specific distribution patterns of PNs were progressively reconstituted. At 5 months postinjection, they could not be distinguished from those in untreated tissue. In contrast to such transient changes, a diffuse chondroitin-sulphate proteoglycan immunoreactivity persisted in the neuropil. Loss of neurons or alterations of their structure as well as reactions of glial cells were not observed. We conclude from this study that PNs, enzymatically destroyed in the adult rat brain, can be completely reconstituted, but the restoration of their extracellular-matrix components needs several months.

Age Factors↗

PubMed1994

Smooth muscle cell expression of extracellular matrix genes after arterial injury.

Accumulation of extracellular matrix (ECM) after arterial injury is an important event in the development of intimal thickening and is modulated by heparin. To investigate the regulation of matrix protein expression, we have analyzed messenger RNA levels by Northern blotting for various ECM proteins in the rat carotid artery balloon injury model. RNA was extracted from normal arteries and from intima-medial preparations at 2 days, 1 week, 2 weeks, and 4 weeks after balloon injury of arteries in animals receiving either saline or heparin infusion. Transcripts for the heparan sulfate proteoglycans perlecan, syndecan, and ryudocan; the chondroitin sulfate proteoglycan versican; the dermatan sulfate proteoglycan biglycan; type I procollagen; and tropoelastin all were increased on Northern blots beginning at 1 week after injury. By in situ hybridization, the transcripts for elastin nd biglycan were primarily localized to smooth muscle cells in the intima and were diminished by heparin in proportion to the decrease in intimal mass. Other matrix genes (perlecan, ryudocan) were expressed in the intima and media and were not affected by heparin. The results support the conclusion that ECM gene expression is a relatively late event in the response of the carotid artery, and that some of the genes are expressed only in the intima whereas others are expressed in both the intima and media.

Animals↗

PubMed2005

Gene expression in tissue associated with extracellular matrix modified ePTFE.

Previous studies have established that surface modification of ePTFE with extracellular matrix molecules promotes vascularization within and around the implanted material. To understand the molecular basis of this tissue response to modified ePTFE, we analyzed large-scale gene expression in nonmodified and extracellular matrix-modified ePTFE-associated healing. Using a microarray containing 15,000 unique mouse cDNAs and an ANOVA-based analysis, we identified 789 genes related to cell signaling, inflammation, matrix remodeling, and proliferation that were differentially expressed across time, between modifications, or both. Genes were clustered based upon similarity in gene expression, producing 7 unique temporal super-patterns of expression. The clustered data revealed 3 general expression patterns unique to tissue surrounding the nonmodified ePTFE, while 6 unique expression patterns were associated with extracellular matrix-modified ePTFE. The more diverse expression patterns associated with extracellular matrix-modified ePTFE suggests that the tissue surrounding the extracellular matrix-modified ePTFE is more dynamic in terms of transcriptional activity. Taken together, these clusters serve as a "genetic fingerprint" for tissue healing in response to a specific material or material modification. Use of these genetic profiles will aid in the pursuit of improved device biocompatibility and enhanced material function.

Animals↗

PubMedDate not supplied

[The spatial-temporal organization of the extracellular matrix].

Data on composition and structure of extracellular matrix (ECM) of different tissues and at different developmental stages are summarized. ECM secreted by cells is a complex supermolecular structure formed of polymerized collagen, elastin, proteoglycans, and structural glycoproteins. Its organization varies depending on tissue type or on location within the same tissue. Variation of ECM composition is determined by qualitative and quantitative differences in combination of its constituent components, as well as by microheterogeneity of these components. Permanent feed-back exists between cells and ECM. Morphological and functional relationships are established between basal membranes, ECM, pericellular matrix, and cytoskeleton. An important role in these relationships belongs to integrins, a family of transmembrane proteins specifically interacting with ECM components. ECM composition specifically changes during development and regeneration, correlating with differentiation and morphogenesis of corresponding tissues. Thus, ECM has a complex structure, is responsible, to a certain extent, for tissue specificity and for stage-specific differences between tissues, and can be regarded as a probable position information carrier, both in embryos and adult animals.

Aging↗

PubMed1988

Synthesis of extracellular matrix glycoproteins by a differentiated thyroid epithelial cell line.

We examined the synthesis of extracellular matrix macromolecules by the differentiated rat thyroid epithelial cell line FRTL-5. As shown by electron microscopy, the extracellular material produced by these cells is deposited at the basolateral surface and focally organized in the form of a basement membrane. Biochemical and biosynthetic studies demonstrated that laminin, type IV collagen, and fibronectin are synthesized and deposited in the culture monolayer. Secretion of fibronectin into the culture medium also occurred. By immunofluorescence we observed some peculiarities in the distribution patterns of the basement membrane glycoproteins; while fibronectin and laminin had an almost superimposable distribution, type IV collagen displayed a rather different pattern. Type IV collagen and laminin localization at sites where extracellular material was detected was confirmed by immuno electronmicroscopy using the protein A-colloidal gold technique. The results indicate that under appropriate culture conditions the differentiated thyroid epithelial cell line FRTL-5 synthesizes, secretes and organizes an extracellular matrix where some basement membrane glycoproteins are present.

Animals↗

PubMed2001

Lefty contributes to the remodeling of extracellular matrix by inhibition of connective tissue growth factor and collagen mRNA expression and increased proteolytic activity in a fibrosarcoma model.

Homeostasis of the extracellular matrix (ECM) of tissues is regulated by controlling deposition and degradation of ECM proteins. The breakdown of ECM is essential in blastocyst implantation and embryonic development, tissue morphogenesis, menstrual shedding, bone formation, tissue resorption after delivery, and tumor growth and invasion. TGF-beta family members are one of the classes of proteins that actively participate in the homeostasis of ECM. Here, we report on the effect of lefty, a novel member of the TGF-beta family, on the homeostasis of extracellular matrix in a fibrosarcoma model. Fibroblastic cells forced to express lefty by retroviral transduction lost their ability to deposit collagen in vivo. This event was associated with down-regulation of the steady-state level of connective tissue growth factor that induces collagen type I mRNA. In addition, lefty transduction significantly decreased collagen type I mRNA expression and simultaneously increased collagenolytic, gelatinolytic, elastolytic, and caseinolytic activities in vivo by the transduced fibroblasts. These findings provide a new insight on the actions of lefty and suggest that this cytokine plays an active role in remodeling of the extracellular matrix in vivo.

Animals↗

PubMed1996

Tenascin is an ubiquitous extracellular matrix protein of human renal interstitium in normal and pathologic conditions.

Tenascin, a large oligomeric glycoprotein, is a recent addition to a list of increasing extracellular matrix proteins. Previous studies have documented the strong expression of tenascin in embryonic kidney and in both normal and abnormal mature glomeruli implicating an important role of this extracellular matrix protein in nephrogenesis and glomerular scarring. Whether tenascin plays any role in interstitial fibrosis, a common final pathway of tubulointerstitial nephritis, is no known; on the other hand, a detailed knowledge of the structural components of interstitial fibrosis is essential for further studies on other fundamental aspects of this biologically and clinically important process. In this study, the expression of tenascin in the renal interstitium was immunohistochemically evaluated in 208 renal specimens during normal kidney (23 cases), acute tubular necrosis (8), acute tubulointerstitial nephritis (8), chronic primary tubulointerstitial nephritis (30), tubulointerstitial nephritis secondary to glomerular diseases of mild (46) and severe (55) degree, ischemic damage (24), and rejection (14). It was found that in normal kidney tenascin expression was limited to the medullary interstitium. In kidney with tubulointerstitial nephritis, tenascin was ubiquitously and constantly expressed in any areas with tubulointerstitial damage regardless of diagnosis, etiology, the cortical vs. medullary location of the lesions, stage of the fibrogenetic process, density of fibroblasts, or severity of interstitial inflammation in the affected areas. Indeed, strong tenascin expression was seen in areas where there was only interstitial edema or inflammation as judged by routine light microscopic preparations. In summary, this study systematically documents tenascin as a novel extracellular matrix protein selectively expressed in the medullary interstitium in normal kidney, and ubiquitously present in areas with interstitial fibrosis.

Antibody Specificity↗

PubMed1990

Plasminogen activator mediated degradation of subendothelial extracellular matrix by human squamous carcinoma cell lines.

Extracellular matrix (ECM) produced by bovine corneal endothelial cells was used to investigate the role of the plasminogen activator/plasmin system in the degradation of ECM by human squamous cell carcinoma (SqCCs) and human foreskin epidermal cells (HFEC). SqCCs caused an 8- to 34-fold greater solubilization of 3H-glucosamine-labeled ECM than HFEC. This action in SqCCs was dependent upon the presence of acid-treated serum, indicating that tumor-associated proteinases were sensitive to the inhibitory action of acid-labile proteinase inhibitors present in the serum. SqCC mediated digestion of radiolabeled ECM was decreased by 14- to 55-fold in plasminogen depleted serum, and the addition of 100 micrograms/mL of purified human plasminogen resulted in up to a 30-fold increase in the degradation of the ECM. Inhibitors of this proteinase system and murine monoclonal antibodies (MAb) specific for human urokinase plasminogen activator (uPA) decreased the SqCC mediated digestion of radiolabeled ECM in a concentration dependent manner. SqCCs exhibited 10- to 30-fold higher extracellular uPA levels than HFEC, as assayed by substrate hydrolysis, zymography, micro-ELISA, western analysis, and northern analysis. These findings reflect the differential ability of these cell types to degrade the ECM. In addition, immuno-cross-reactive plasminogen activator inhibitor type I (PAI type 1) and type II (PAI type 2) were identified in cell-free conditioned medium produced by both tumor cells and normal epidermal cells, using a micro-ELISA assay. Indirect immunofluorescence flow cytometry, employing MAbs directed against uPA, detected the presence and localization of uPA on the SqCC cell surface. These findings were specific for uPA, since cell surface associated tissue plasminogen activator was not detected in these cell types under analogous conditions. In addition, partially purified SqCC plasma membrane preparations exhibited 2- to 10-fold higher uPA-like activity than HFEC, as determined by zymography. The findings support the concept that the plasminogen activator system is important in the breakdown of ECM by SqCCs and suggest that regulatory mechanisms involved in this proteolytic system may be important targets for chemotherapeutic intervention to limit tumor cell invasion and metastasis.

Antibodies, Monoclonal↗

PubMed2005

Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix.

Airway remodeling describes the structural changes that occur in the asthmatic airway that include airway smooth muscle hyperplasia, increases in vascularity due to angiogenesis, and thickening of the basement membrane. Our aim in this study was to examine the effect of transforming growth factor-beta on the release of connective tissue growth factor and vascular endothelial growth factor from human airway smooth muscle cells derived from asthmatic and nonasthmatic patients. In addition we studied the immunohistochemical localization of these cytokines in the extracellular matrix after stimulating bronchial rings with transforming growth factor-beta. Connective tissue growth factor and vascular endothelial growth factor were released from both cell types and colocalized in the surrounding extracellular matrix. Prostaglandin E2 inhibited the increase in connective tissue growth factor mRNA but augmented the release of vascular endothelial growth factor. Matrix metalloproteinase-2 decreased the amount of connective tissue growth factor and vascular endothelial growth factor, but not fibronectin deposited in the extracellular matrix. This report provides the first evidence that connective tissue growth factor may anchor vascular endothelial growth factor to the extracellular matrix and that this deposition is decreased by matrix metalloproteinase-2 and prostaglandin E2. This relationship has the potential to contribute to the changes that constitute airway remodeling, therefore providing a novel focus for therapeutic intervention in asthma.

Adolescent↗

PubMed1986

Melanoma cell adhesion to defined extracellular matrix components.

The binding of mouse B16-F10 melanoma cells to defined extracellular matrix components was studied using a dot-blot cell attachment assay. Radiolabeled melanoma cells adhered to immobilized elastin and laminin. Reduced binding was seen with fibronectin, collagen types I and IV, heparan sulfate, and bovine serum albumin. No adhesive activity was found in elastin associated microfibrillar proteins or in elastin fragments generated by alkali or acid digestion. Adherence to extracellular matrix components has been suggested to play a role in tumor spread to secondary sites. Our results indicate that elastin and laminin are the major extracellular molecules responsible for melanoma cell adhesion.

Amino Acids↗

PubMed1987

Gastrulation in the sea urchin embryo requires the deposition of crosslinked collagen within the extracellular matrix.

This study demonstrates that a collagenous extracellular matrix (ECM) is necessary for gastrulation in the sea urchin embryo. The approach taken was to disrupt collagen processing with two types of agents (a lathyritic agent, beta-aminopropionitrile (BAPN), and three types of proline analogs: dehydroproline, cis-OH-proline, and azetidine carboxylic acid) and to assess the effect on embryogenesis by morphological, immunological, and biochemical criteria. Embryos chronically exposed to either of the agents following fertilization displayed no detectable developmental abnormalities before the mesenchyme blastula stage. These embryos, however, did not gastrulate nor differentiate any further and remained at the mesenchyme blastula stage for at least 36 hr. Upon removal of the agents, the embryos resumed a normal developmental schedule and formed pluteus larvae that were indistinguishable from control embryos. By immunofluorescence studies with monospecific antibodies to type I and type IV collagens it is seen that the lathyritic agent BAPN reduces the accumulation of collagens within the ECM. This effect is confirmed and quantitated by use of an ELISA and by a biochemical determination of OH-proline. When the agents are removed from the inhibited embryos, collagen deposition returns to normal, coincident with gastrulation. Western-blot analysis, using monospecific antibodies to collagen, demonstrates that the effect of the lathyritic agent is to reduce the stability of the extracellular collagen by inhibiting the intra- and intermolecular crosslinking of collagen molecules. BAPN exhibits a dose-dependent effect on morphogenesis, but has no effect on respiration nor on protein synthesis of the embryos throughout development. Although the lathyritic agent affects collagen deposition, it is shown to not affect the expression of other molecules of the ECM, nor that of several cell surface molecules. However, a cell surface molecule that is expressed specifically in the endoderm, termed Endo 1, is not expressed in the inhibited embryos. Endo 1 is expressed after removal of the lathyritic agent and its appearance is coincident with gastrulation in the recovered embryos. These results suggest that a collagenous ECM is important for gastrulation and subsequent differentiation in the sea urchin, but not for earlier developmental processes. In addition, the dependence of Endo 1 expression on the collagenous ECM raises the possibility that this cell surface molecule is in some way regulated by interactions of the presumptive endodermal cells with the ECM.

Aminopropionitrile↗