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PubMed2004

Eosinophils adhere to vascular cell adhesion molecule-1 via podosomes.

Vascular cell adhesion molecule (VCAM)-1 supports specific eosinophil adhesion via alpha4beta1 integrin. We tested the hypothesis that adhesive contacts formed by eosinophils on VCAM-1 are different from focal adhesions formed by adherent fibroblasts. Eosinophils adherent on VCAM-1 formed punctate adhesions that fit the criteria for podosomes, highly dynamic structures found in adherent transformed fibroblasts, osteoclasts, and macrophages. The structures contained beta1 integrin subunit, phosphotyrosine-containing proteins, punctate filamentous actin, and gelsolin, a podosome marker. In contrast, nontransformed fibroblasts on VCAM-1 formed peripheral focal adhesions that were positive for alpha4, beta1, phosphotyrosine, vinculin, talin, and paxillin; negative for gelsolin; and associated with microfilaments. Phorbol myristate acetate or tumor necrosis factor-alpha and interleukin-5 stimulated podosome formation in adherent eosinophils. Because podosomes in tumor cells are associated with extracellular matrix degradation, we analyzed the VCAM-1 layer. VCAM-1 was lost under adherent eosinophils but not under adherent fibroblasts. This loss was inhibited by the metalloproteinase inhibitor ortho-phenanthroline and correlated with expression and podosome localization of a membrane-tethered metalloproteinase, a disintegrin and metalloproteinase domain 8. Podosome-mediated VCAM-1 clearance may be a mechanism to regulate eosinophil arrest and extravasation in allergic conditions such as asthma.

Actin Cytoskeleton↗
PubMed2005

Integrin alpha2beta1 modulates EGF stimulation of Rho GTPase-dependent morphological changes in adherent human rhabdomyosarcoma RD cells.

The ability of cells to undergo shape changes is essential for diverse cellular functions including cell growth, differentiation, and movement. The present study examines how an integration of the function of alpha2beta1 integrin with that of the receptor for epidermal growth factor (EGFR) modulates EGF-stimulated morphological changes in human rhabdomyosarcoma RD transfectant cells. Upon EGF stimulation, RD transfectant cells that lacked alpha2beta1 integrin expression (RDpF) underwent contraction; in contrast, expression of alpha2beta1 on RD cells (RDX2C2) resulted in transient cell spreading. Integrin alpha2 cytoplasmic domain played a critical role in the observed alpha2beta1-mediated conversion from a cell rounding to a cell spreading phenotype. Thus, the expression of an alpha2 cytoplasmic domain deletion variant (X2C0) or a chimeric alpha2beta1 containing the cytoplasmic domain of alpha4 (X2C4) or alpha5 (X2C5), instead of alpha2, failed to mediate spreading upon EGF stimulation. Using dominant negative (DN) mutants of RhoGTPases, results revealed that RhoA activation was required for both EGF-stimulated responses of cell rounding and spreading, Cdc42 functioned in the re-spreading of cells after undergoing EGF-stimulated contraction, and Rac1 was required in alpha2beta1-mediated RD cell spreading. Therefore, alpha2beta1 integrin function can switch the Rho GTPase-dependent cell shape changes in RD cells from an EGF-stimulated cell contraction to a spreading morphology. Together, results show that integrin alpha2 cytoplasmic domain plays an indispensable role in the ability of integrin alpha2beta1 to modulate EGF stimulation of Rho-GTPase-dependent morphological changes in RD cells.

Animals↗
PubMed2003

Laminin isoforms in fetal and adult human adrenal cortex.

Laminin has been proposed to influence the function of human adrenal cortex. We have studied the distribution of laminin (Ln) chains using immunofluorescence in human fetal and adult adrenal cortex. In the fetal gland Ln alpha2- and alpha5-chains were weakly expressed in the definitive zone, whereas Ln alpha4-, beta1-, and gamma1-chains occurred around vessels. In the adult gland, Ln alpha2-, alpha5-, and gamma1-chains were found in epithelial basement membranes (BM) in all cortical zones, Ln alpha4-chain in vessels, Ln beta1-chain in outer zone, and Ln beta2-chain in the two inner zones of the cortex, respectively. Among the integrins in adult gland, integrin alpha(3)-subunit was confined to basal surfaces of cortical cells, alpha(6) to vessels, alpha(1) to the stroma, and alpha(2) diffusely to epithelial cells. Lutheran glycoprotein and dystroglycan occurred in the fetal gland diffusely in the definitive zone and throughout the epithelium in the adult. The isoform composition of BM of the adult adrenal gland is distinct, with Ln-2 and -10 in BM of the outer zone and Ln-4 and -11 in BM of the two inner zones. The results suggest that integrin alpha(3)beta(1) and Lutheran are candidate receptors for Ln-10 and -11, whereas dystroglycan probably binds Ln-2 and -4.

Adrenal Cortex↗
PubMed2000

A novel RGD-independent fibronectin assembly pathway initiated by alpha4beta1 integrin binding to the alternatively spliced V region.

Fibronectin (FN) matrix assembly is a multi-step process that involves binding to integrin receptors, FN-FN interactions and connections to the actin cytoskeleton. Ultimately, FN is converted into stable matrix fibrils that are detergent-insoluble. RGD-binding integrins such as alpha5beta1 play a major role in the assembly of fibrillar FN. Here we show that alpha4beta1 binding to the alternatively spliced V (IIICS) region of FN initiates an alternative assembly pathway. Activation of alpha4beta1 with exogenous agents such as Mn(2+) or a beta1-stimulatory antibody TS2/16 was sufficient to induce initiation of FN fibrillogenesis by Ramos B lymphoma cells and by CHO(B2)alpha4 cells. Using recombinant FNs lacking specific sequences, we show that assembly is independent of the RGD sequence but requires the V25/CS-1 segment. Previously, we have characterized an activated recombinant FN (FN III(1-7)) that rapidly forms detergent-insoluble multimers upon binding to alpha5beta1 integrin. Alpha4beta1 also formed FNdeltaIII(1-7) multimers without the aid of exogenous stimulants, suggesting that an activated form of FN can override the need for activation of the integrin. In contrast to assembly by alpha5beta1, actin filaments remained largely cortical and no change in cell growth rate was observed with alpha4beta1-mediated assembly. These results show that binding sites on FN other than the RGD sequence/synergy site and distant from the cell binding domain can promote FN assembly. Thus, there appear to be multiple, integrin-specific mechanisms for assembly of FN matrix.

Alternative Splicing↗
PubMed1997

Analysis of the activation state of alpha4beta1 integrin in human B cell lines derived from myeloma, leukemia or lymphoma.

Myeloma cells specifically localize in the bone marrow and rarely circulate in blood. To study whether this immobilization could be partially explained by the presence of constitutively activated integrins, particularly alpha4beta1, we used the activation reporter HUTS-21 anti-beta1 mAb. These analyses showed that beta1 integrins on myeloma cells were moderately active and could be upregulated similarly to integrins on lymphoma or leukemia cells. Myeloma cells were also tested for their ability to attach to RGD-containing fibronectin fragments, a property of activated (but not resting) alpha4beta1. Two cell lines adhered to these fragments and this was inhibited by anti-alpha5 but not by anti-alpha4 mAbs. These results show that myeloma cells bear low/moderately active alpha4beta1 and support the notion that multiple interactions contribute to their localization in the bone marrow.

B-Lymphocytes↗
PubMed2004

Laminins alpha2 and alpha4 in pancreatic acinar basement membranes are required for basal receptor localization.

Basement membranes (BMs) are thin layers of extracellular matrix (ECM) found at the basal surface of many cell types, including epithelial cells. BMs present growth, differentiation, and anti-apoptotic signals and provide structural support to cells, compartmentalize tissues, and serve as filters. The structure and function of BMs depend on their complement of laminins, a family of alpha beta gamma heterotrimeric glycoproteins. We found that laminins containing the alpha2 and alpha4 chains are the major laminins in pancreatic acinar BMs. Importantly, these laminins were required for proper basal localization on acinar cells of two laminin receptors, dystroglycan and integrin alpha6beta4 .

Animals↗
PubMed1996

VLA-5 in the plasma cell line, FR4ds, acts as a common regulator of VLA-4 and VLA-6 in spreading induced by fibronectin and laminin.

VLA-5 recognizes the GRGDSP sequence of fibronectin (FN) in the extracellular matrix (ECM). We examined the role of beta1 integrin in the spreading of the human plasma cell line, FR4ds, induced by FN and laminin (LN). We first examined the role of VLA-5 in the spreading induced by FN. Anti-alpha4 antibody induced 46.4% inhibition, whereas anti-alpha5 had no effect. A combination of anti-alpha4 and anti-alpha5 enhanced the inhibition of spreading significantly. Complementary inhibition was also demonstrated using the GRGDSP peptide plus anti-alpha4 and the GRGDNP peptide of LN plus anti-alpha4. The results suggested that VLA-5 is a regulator of VLA-4 and that it is involved in the recognition of GRGDNP. We then examined the role of VLA-5 in the spreading induced by LN. Anti-alpha6 induced 53.1% inhibition. Anti-alpha5 alone had no effect. A combination of alpha5 and anti-alpha6, however, significantly enhanced the inhibition of spreading. The combination of GRGDSP plus anti-alpha6 and GRGDNP plus anti-alpha6 resulted in complete inhibition. These results suggested that VLA-5 participates in the recognition of LN cooperatively with VLA-6 and that VLA-5 is a common regulator of VLA-4 and the LN receptor, VLA-6.

Cell Movement↗
PubMed2001

Preferential production of interferon-gamma by CD4+ T cells expressing the homing receptor integrin alpha4/beta7.

Recent studies indicate that T helper type 1 (Th1) and 2 (Th2) lymphocytes differ in their expression of molecules that control T-cell migration, including adhesion molecules and chemokine receptors. We investigated the relationship between cytokine production and expression of the homing receptor integrin alpha4/beta7 on T cells. We began by analysing cytokine production by human CD4+ CD45RA- memory/effector T cells following brief (4 hr) stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. alpha4/ beta7high CD4+ T cells were more likely to produce the Th1 cytokine interferon-gamma (IFN-gamma) than were alpha4/beta7- CD4+ T cells in all six subjects studied. In contrast, production of the Th2 cytokine interleukin-4 (IL-4) was similar on alpha4/ beta7high and alpha4/beta7- CD4+ T cells. In addition, we found that human CD4+ CD45RA- T cells that adhered to the alpha4/beta7 ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1) had a greater capacity to produce IFN-gamma than did non-adherent cells, suggesting that the association between alpha4/beta7 expression and IFN-gamma production has functional significance. These results suggested that primary activation under Th1-promoting conditions might favour expression of alpha4/beta7. We directly examined this possibility, and found that naïve murine CD4+ T cells activated under Th1-promoting conditions expressed higher levels of alpha4/beta7 compared to cells activated under Th2-promoting conditions. The association between alpha4/beta7 expression and IFN-gamma production by CD4+ T cells may help to determine the cytokine balance when MAdCAM-1 is expressed at sites of inflammation in the intestine or elsewhere.

Adult↗
PubMed2000

Expression of mRNAs encoding for alpha and beta integrin subunits, MMPs, and TIMPs in stretched human periodontal ligament and gingival fibroblasts.

The biological mechanisms of tooth movement result from the cellular responses of connective tissues to exogenous mechanical forces. Among these responses, the degradation of the extracellular matrix takes place, but the identification of the molecular basis as well as the components implicated in this degradation are poorly understood. To contribute to this identification, we subjected human fibroblasts obtained from the periodontal ligament (PDLs) and from the gingiva (HGFs) to a continuous stretch to quantify the mRNAs encoding for various metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and alpha and beta integrin subunits. Both cell lines reacted by inducing the expression of the mRNAs encoding for MMP-1, MMP-2, TIMP-1, and TIMP-2, while other mRNAs did not vary (MT1-MMP, TIMP-3) or were not expressed (MMP-9). PDLs expressed selectively the mRNAs encoding for alpha4 and alphav, with no difference measurable under stretching, while the mRNAs encoding for alpha6 and beta1 were increased and the one encoding for alpha5 was decreased. HGFs increased the mRNAs encoding for alpha2, alpha6, beta1, and beta3 and decreased the one encoding for alpha3. Analysis of our data indicated that stretched HGFs and PDLs induced the same pattern of mRNAs encoding for MMPs and TIMPs but differed for those encoding various integrin subunits, known to act as protein receptors in mechanotransduction.

Cells, Cultured↗
PubMed2001

Expression of integrin receptors on peripheral lymphocytes: correlation with endometrial receptivity.

PROBLEM: To investigate the expression of integrin (ITG) cell adhesion molecules on peripheral blood lymphocytes (PBL) and their correlation with endometrial cell ITG expression in fertile and infertile women during peak uterine receptive period (day 19/20). METHOD OF STUDY: Surface marker expression and quantification of alpha6, alpha4 and beta3 ITG subunits was done by immunohistochemistry, indirect immunofluroscence and cell-enzyme-linked immunosorbent assay methods using endometrial cells and PBL obtained from fertile and infertile (unexplained infertility) women. RESULTS: The expression of ITGs was significantly (P<0.001) decreased in the endometrial cells of infertile women compared to normal fertile women. These results correlated well with the data obtained using PBL-ITG expression. CONCLUSIONS: If these preliminary data are consistent in a larger group of patients, the expression of alpha4 and beta3-ITG subunits on PBL may be used as clinical markers to assess endometrial receptivity in infertile women. Moreover, frequent blood sampling is advantageous over repeated endometrial biopsies as the former approach is easier, non-traumatic and avoids intra-uterine infections.

Adult↗
PubMed2002

Chondroitin sulphate modification in the alpha4 chain of human recombinant laminin-8 (alpha4beta1gamma1).

We have produced human laminin-8 (alpha4beta1gamma1) using recombinant technology. Approximately half of the recombinant laminin-8 (rLN-8) molecules were found to have a chondroitin sulphate modification in the alpha4 chain. The substituted and non-substituted forms were separated and tested for cell adhesion activity. Lower cell adhesion promoting activity was seen for the substituted form, but the integrin receptor utilization was similar. We also found the human rLN-8 to behave identically in cell adhesion assays compared to a human/mouse hybrid variant of rLN-8.

Animals↗
PubMed1996

Beta1 integrin-mediated activation of focal adhesion kinase and its association with Fyn and Zap-70 in human NK cells.

Adhesive interactions mediated by cell surface receptors have been shown to induce signal transduction pathways that regulate changes in cellular function. We have reported recently that fibronectin (FN) receptors, alpha4beta1 and alpha5beta1 integrins, on NK cells transduce transmembrane signals leading to tyrosine phosphorylation of 60-, 70-, and 120-kDa proteins. In the current study, we have identified a 120-kDa phosphoprotein as the focal adhesion kinase (p125FAK), a structurally unique nonreceptor protein tyrosine kinase that localizes to focal adhesions. Activity of p125FAK was induced by adhesion of NK cells to plastic-immobilized FN, by cross-linking of cell surface-bound FN or FN fragments, FN120 or FN40, with anti-FN mAb, or by cross-linking of alpha4beta1 or alpha5beta1 integrins with alpha-chain-specific Abs. We also observed that enhanced in vitro kinase activity was associated with immunoprecipitates of alpha4beta1 or alpha5beta1 integrins from lysates of FN-adherent NK cells as compared with BSA-treated NK cells. In addition to p125FAK activity, FN-induced kinase activity was also found to be mediated by Fyn, Lyn, and Zap-70, as assessed by in vitro phosphorylation of the immunoprecipitated kinases in the presence of [gamma-32P]ATP. Clustering of FN receptors on NK cells by agonists such as immobilized FN or alpha4- or alpha5-specific Abs also induced association of Fyn and Zap-70 with p125FAK. Our observations indicate that activation and phosphorylation of p125FAK as well as Zap-70 and certain kinases of the src family play an important role in formation of active signaling complexes in response to triggering via beta1 integrins on NK cells. These results also suggest the existence of cross-talk or points of convergence between the beta1 integrin-mediated and other receptor-signaling pathways.

Cell Adhesion↗
PubMed2004

Mechanism of CD47-induced alpha4beta1 integrin activation and adhesion in sickle reticulocytes.

We recently reported that CD47 (integrin-associated protein) on sickle red blood cells (SS RBCs) activates G-protein-dependent signaling, which promotes cell adhesion to immobilized thrombospondin (TSP) under relevant shear stress. These data suggested that signal transduction in SS RBCs may contribute to the vaso-occlusive pathology observed in sickle cell disease. However, the CD47-activated SS RBC adhesion receptor(s) that mediated adhesion to immobilized TSP remained unknown. Here we demonstrate that the alpha4beta1 integrin (VLA-4) is the receptor that mediates CD47-stimulated SS RBC adhesion to immobilized TSP. This adhesion requires both the N-terminal heparin-binding domain and the RGD site of TSP. CD47 signaling induces an "inside-out" activation of alpha4beta1 on SS RBCs as indicated by an RGD-dependent interaction of this integrin with soluble, plasma fibronectin. However, CD47 engagement also induces an alpha4beta1-mediated, RGD-independent adhesion of SS RBCs to immobilized vascular cell adhesion molecule-1 (VCAM-1). CD47 signaling in SS RBCs appears to be independent of large scale changes in cAMP formation but nonetheless promotes alpha4beta1-mediated adhesion via a protein kinase A-dependent, serine phosphorylation of the alpha4 cytoplasmic domain. CD47-activated SS RBC adhesion absolutely requires the Src family tyrosine kinases and is also enhanced by treatment of SS RBCs with low concentrations of cytochalasin D, which may release alpha4beta1 from cytoskeletal restraints. In addition, CD47 co-immunoprecipitates with alpha4beta1 in a sickle reticulocyte-enriched fraction of SS RBCs. These studies therefore identify the alpha4beta1 integrin on SS RBCs as a CD47-activated receptor for TSP, VCAM-1, and plasma fibronectin, revealing novel binding characteristics of this integrin.

Anemia, Sickle Cell↗
PubMed2002

alpha4beta1 integrin regulates lamellipodia protrusion via a focal complex/focal adhesion-independent mechanism.

alpha4beta1 integrin plays an important role in cell migration. We show that when ectopically expressed in Chinese hamster ovary cells, alpha4beta1 is sufficient and required for promoting protrusion of broad lamellipodia in response to scratch-wounding, whereas alpha5beta1 does not have this effect. By time-lapse microscopy of cells expressing an alpha4/green fluorescent protein fusion protein, we show that alpha4beta1 forms transient puncta at the leading edge of cells that begin to protrude lamellipodia in response to scratch-wounding. The cells expressing a mutant alpha4/green fluorescent protein that binds paxillin at a reduced level had a faster response to scratch-wounding, forming alpha4-positive puncta and protruding lamellipodia much earlier. While enhancing lamellipodia protrusion, this mutation reduces random motility of the cells in Transwell assays, indicating that lamellipodia protrusion and random motility are distinct types of motile activities that are differentially regulated by interactions between alpha4beta1 and paxillin. Finally, we show that, at the leading edge, alpha4-positive puncta and paxillin-positive focal complexes/adhesions do not colocalize, but alpha4beta1 and paxillin colocalize partially in ruffles. These findings provide evidence for a specific role of alpha4beta1 in lamellipodia protrusion that is distinct from the motility-promoting functions of alpha5beta1 and other integrins that mediate cell adhesion and signaling events through focal complexes and focal adhesions.

Animals↗
PubMed1999

Functional expression of beta1 and beta2 integrins on tumor infiltrating lymphocytes (TILs) in colorectal cancer.

Integrins play an important role in various lymphocyte functions. In this study, tumor-infiltrating lymphocytes (TIL) were isolated from colorectal cancer tissues and the expression of beta1 and beta2 integrins on the TIL was quantitatively examined with two-color flow cytometry. In comparison with peripheral blood lymphocytes (PBL), TIL expressed a lower level of common beta1 chain (CD29) in both CD4 and CD8 subpopulations. Among the associated alpha chains, the expressions of alpha1 (CD49a) and alpha2 (CD49b) were slightly higher in TIL than in PBL, whereas alpha4 (CD49d) and alpha6 (CD49f) were markedly downregulated in TIL. Both alphaL (CD11a) and beta2 (CD18) were reduced in CD8(+) TIL but not in CD4(+) TIL. TIL with the CD8(+) cytotoxic phenotype showed significantly decreased binding to purified intracellular adhesion molecules (ICAM)-1, and vascular adhesion cell molecule (VCAM)-1, and HT29 colon cancer cells, compared with the in counterparts in PBL. The peculiar expression pattern and functional down regulation of these integrins may explain why TIL in colorectal cancer cannot eradicate the malignant cells.

Aged↗
PubMed1998

Integrins involved in the adhesion of megakaryocytes to fibronectin and fibrinogen.

We studied integrins involved in the adhesion of resting and activated megakaryocytes (MK) to fibronectin (FN) and fibrinogen (FGN). Guinea pig MK were isolated and in some experiments were activated by thrombin. MK adhering to FN or FGN coated on coverslips were quantitated by a computerized image analysis program. The binding of soluble human FN to MK was detected by Western blotting. Anti-integrin antibodies, disintegrins, and cyclic RGD peptides were used to identify integrins involved in the adhesion of MK to FN or FGN. Resting MK adhered to coverslips with immobilized FN. The adhesion of MK to FN was primarily inhibited by an anti-alpha5 antibody and EMF-10, a distintegrin highly specific for alpha5 beta1. However, the adhesion of MK to FN was not blocked by agents that inhibit alphaIIb beta3, alphav beta3 or alpha4 beta1. A beta1 activating antibody increased the number of MK bound to FN due to the activation of alpha5 beta1. The binding of soluble FN was also primarily inhibited by agents that block alpha5 beta1. Resting MK did not adhere to FGN. However, MK activated by thrombin did adhere to FGN. This binding was mediated by alphaIIb beta3, because binding was inhibited by bitistatin, a disintegrin, and a cyclic RGD peptide that are known to block this integrin. The binding of thrombin-activated MK to FN was mediated by both alpha5 beta1 and alphaIIb beta3 based on the additive effect of agents that inhibit these integrins. The study indicates that resting MK bind to FN but not to FGN and that alpha5 beta1 is the major integrin involved in the binding of MK to FN. Activated MK bind to FGN primarily by alphaIIb beta3. However, the binding of activated MK to FN is due to both alpha5 beta1 and alphaIIb beta3. The demonstration that alpha5 beta1 and that alphaIIb beta3 are involved in MK adhesion indicates that these integrins may have a role in MK maturation and platelet production.

Animals↗
PubMed2006

Laminin expression by human periodontal ligament fibroblasts.

Our previous study demonstrated that a laminin-like molecule produced by periodontal ligament fibroblasts (PLFs) induces gingival epithelial cell chemotaxis. The aim of this study was to identify the laminin isoforms that are expressed by PLFs. Proteins in PLF-conditioned medium from serum-free cultures were separated by gel filtration followed by gelatin-affinity chromatography to remove fibronectin. Protein expression of laminin isoforms was determined using Western blotting, and mRNA expression was examined by RT-PCR. Partially purified laminin evoked gingival epithelial cell chemotaxis, and this activity was blocked by anti-integrin alpha3, alpha6, and beta1 antibodies. Although RT-PCR analysis showed PLFs expressed laminin alpha1 to alpha5, beta1 to beta3, gamma1, and gamma2 chain mRNAs, the predominant laminin chains detected by Western blotting were alpha4, alpha2, beta1, beta2, and gamma1. These results suggest that PLFs secrete mainly laminin-8/9 (alpha4beta1gamma1/alpha4beta2gamma1) and laminin-2/4 (alpha2beta1gamma1/alpha2beta2gamma1). PLF-derived laminins may be involved in the pathogenesis and progression of periodontitis by inducing apical migration of epithelial cells in certain circumstances.

Antibodies, Blocking↗
PubMed2001

Central role of the alpha4beta1 integrin in the coordination of avian truncal neural crest cell adhesion, migration, and survival.

Based on functional and histological studies, the fibronectin receptor of the integrin family alpha4beta1 has been ascribed a critical role during neural crest cell migration in the vertebrate embryo. In the present study, because integrins have been shown to participate in multiple basic cellular processes, including cell adhesion, migration, survival, proliferation, and differentiation, we have reexamined in detail the role of alpha4beta1 during avian truncal neural crest cell migration. RT-PCR and immunocytochemical studies revealed that migrating neural crest cells but not premigratory cells explanted in vitro expressed detectable levels of alpha4 messengers and proteins suggesting that alpha4beta1 expression was induced at the time of the initiation of the migration phase. In agreement with this observation, antibody inhibition of alpha4beta1 activity in vitro resulted in a strong, immediate and sustained reduction of neural crest cell motion on fibronectin, as judged on videomicroscopy analyses, but apparently did not prevent their delamination from the neural tube. However, alpha4beta1 appeared to exhibit a broader role in the control of cell migration on a variety of extracellular matrix molecules, presumably by regulating cellular events downstream from integrins. Moreover, blocking alpha4beta1 function caused a severe increase in apoptotic cell death among the neural crest population without influencing notably cell proliferation. Collectively, these results indicate that, notwithstanding its critical implication in cell motion, alpha4beta1 integrin could play a central role in neural crest cell development by coordinating multiple cellular events, such as cell adhesion, locomotion, and survival.

Animals↗