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M Kedinger

Publications and source records attributed to M Kedinger.

At least 37 records · Page 2Linked to original sources
PubMed1998

The Cdx-1 and Cdx-2 homeobox genes in the intestine.

The past years have witnessed an increasing number of reports relative to homeobox genes in endoderm-derived tissues. In this review, we focus on the caudal-related Cdx-1 and Cdx-2 homeobox genes to give an overview of the in vivo, in vitro, and ex vivo approaches that emphasize their primary role in intestinal development and in the control of intestinal cell proliferation, differentiation, and identity. The participation of these genes in colon tumorigenesis and their identification as important actors of the oncogenic process are also discussed.

Animals↗
PubMed1998

Subepithelial fibroblast cell lines from different levels of gut axis display regional characteristics.

The intestine is characterized by morphofunctional differences along the proximodistal axis. The aim of this study was to derive mesenchymal cell lines representative of the gut axis. We isolated and cloned rat intestinal subepithelial myofibroblasts raised from 8-day proximal jejunum, distal ileum, and proximal colon lamina propria. Two clonal cell lines from each level of the gut were characterized. They 1) express the specific markers vimentin, smooth muscle alpha-actin, and smooth muscle myosin heavy chain, revealed by immunofluorescence microscopy and 2) distinctly support endodermal cell growth in a coculture model, depending on their regional origin, and 3) the clones raised from the various proximodistal regions maintain the same pattern of morphogenetic and growth and/or differentiation factor gene expression as in vivo: hepatocyte growth and/or scatter factor and transforming growth factor-beta 1 mRNAs analyzed by RT-PCR were more abundant, in the colon and ileal clones and mucosal connective tissue, respectively. In addition, epimorphin mRNA studied by Northern blot was also the highest in one ileal clone, in which it was selectively upregulated by all-trans retinoic acid (RA) treatment. Epimorphin expression in isolated 8-day intestinal lamina propria was higher in the distal small intestine and proximal colon than in the proximal small intestine. In conclusion, we isolated and characterized homogeneous cell subtypes that can now be used to approach the molecular regulation of the epithelium-mesenchyme-dependent regional specificity along the gut.

Animals↗
PubMed1997

Key role of the Cdx2 homeobox gene in extracellular matrix-mediated intestinal cell differentiation.

To explore the role of homeobox genes in the intestine, the human colon adenocarcinoma cell line Caco2-TC7 has been stably transfected with plasmids synthesizing Cdx1 and Cdx2 sense and antisense RNAs. Cdx1 overexpression or inhibition by antisense RNA does not markedly modify the cell differentiation markers analyzed in this study. In contrast, Cdx2 overexpression stimulates two typical markers of enterocytic differentiation: sucrase-isomaltase and lactase. Cells in which the endogenous expression of Cdx2 is reduced by antisense RNA attach poorly to the substratum. Conversely, Cdx2 overexpression modifies the expression of molecules involved in cell-cell and cell-substratum interactions and in transduction process: indeed, E-cadherin, integrin-beta4 subunit, laminin-gamma2 chain, hemidesmosomal protein, APC, and alpha-actinin are upregulated. Interestingly, most of these molecules are preferentially expressed in vivo in the differentiated villi enterocytes rather than in crypt cells. Cdx2 overexpression also results in the stimulation of HoxA-9 mRNA expression, an homeobox gene selectively expressed in the colon. In contrast, Cdx2-overexpressing cells display a decline of Cdx1 mRNA, which is mostly found in vivo in crypt cells. When implanted in nude mice, Cdx2-overexpressing cells produce larger tumors than control cells, and form glandular and villus-like structures. Laminin-1 is known to stimulate intestinal cell differentiation in vitro. In the present study, we demonstrate that the differentiating effect of laminin-1 coatings on Caco2-TC7 cells is accompanied by an upregulation of Cdx2. To further document this observation, we analyzed a series of Caco2 clones in which the production of laminin-alpha1 chain is differentially inhibited by antisense RNA. We found a positive correlation between the level of Cdx2 expression, that of endogenous laminin-alpha1 chain mRNA and that of sucrase-isomaltase expression in these cell lines. Taken together, these results suggest (a) that Cdx1 and Cdx2 homeobox genes play distinct roles in the intestinal epithelium, (b) that Cdx2 provokes pleiotropic effects triggering cells towards the phenotype of differentiated villus enterocytes, and (c) that Cdx2 expression is modulated by basement membrane components. Hence, we conclude that Cdx2 plays a key role in the extracellular matrix-mediated intestinal cell differentiation.

Adenocarcinoma↗
PubMed1997

The T3R alpha gene encoding a thyroid hormone receptor is essential for post-natal development and thyroid hormone production.

The diverse functions of thyroid hormones are thought to be mediated by two nuclear receptors, T3R alpha1 and T3R beta, encoded by the genes T3R alpha and T3R beta respectively. The T3R alpha gene also produces a non-ligand-binding protein T3R alpha2. The in vivo functions of these receptors are still unclear. We describe here the homozygous inactivation of the T3R alpha gene which abrogates the production of both T3R alpha1 and T3R alpha2 isoforms and that leads to death in mice within 5 weeks after birth. After 2 weeks of life, the homozygous mice become progressively hypothyroidic and exhibit a growth arrest. Small intestine and bones showed a strongly delayed maturation. In contrast to the negative regulatory function of the T3R beta gene on thyroid hormone production, our data show that the T3R alpha gene products are involved in up-regulation of thyroid hormone production at weaning time. Thus, thyroid hormone production might be balanced through a positive T3R alpha and a negative T3R beta pathway. The abnormal phenotypes observed on the homozygous mutant mice strongly suggest that the T3R alpha gene is essential for the transformation of a mother-dependent pup to an 'adult' mouse. These data define crucial in vivo functions for thyroid hormones through a T3R alpha pathway during post-natal development.

Acetylcholine↗
PubMed1997

Polarized expression of HD1: relationship with the cytoskeleton in cultured human colonic carcinoma cells.

Hemidesmosomes (HDs) mediate adhesion of epithelial cells to the extracellular matrix and have morphological associations with intermediate-size filaments (IFs). Hemidesmosomal molecular components including HD1, the two bullous pemphigoid antigens, and the integrin alpha 6 beta 4 have been identified in HDs of stratified and complex epithelium. In this study, we report that HT29-Fu cells, a human colonic tumor cell line, express two hemidesmosomal components (HD1, alpha 6 beta 4) associated in an adhesion structure termed type II HDs. Immunofluorescence studies showed a colocalization of HD1 and alpha 6 beta 4 in basal patches between actin stress fibers. Using cytochalasin B or vinblastine, two drugs which disrupt the cytoskeleton, we demonstrate that the redistribution of HD1 was probably induced by the reorganization of the basal cytokeratin network. We also show that in vitro HD1 binds to polymerized cytokeratin intermediate filaments; this suggests that HD1 in intestinal epithelial cells functions as a linker protein connecting cytokeratin filaments to the basal plasma membrane, probably through the beta 4 subunit of the integrin alpha 6 beta 4.

Actins↗
PubMed1997

Distribution of cell adhesion molecules in infants with intestinal epithelial dysplasia (tufting enteropathy).

BACKGROUND & AIMS: Intestinal epithelial dysplasia, or tufting enteropathy, is a newly described clinicopathologic entity with refractory diarrhea in infants. Histological abnormalities include villous atrophy, disorganization of the surface epithelium, and basement membrane abnormalities. The aim of this study was to examine defects in intestinal epithelial cell adhesion, differentiation, or proliferation in the pathogenesis of epithelial dysplasia. METHODS: Histological, immunohistochemical, and ultrastructural characteristics of epithelial dysplasia in a group of 6 children were compared with those groups with normal small bowel and other villous atrophy (celiac sprue and microvillous inclusion disease). Distribution of adhesion molecules, markers of cell polarization and proliferation, and the phenotype of intraepithelial lymphocytes were determined. RESULTS: Alterations suggestive of abnormal cell-cell and cell-matrix interactions were present in patients with epithelial dysplasia. They included abnormal distribution of alpha 2 beta 1 integrin along the crypt-villus axis, increased immunohistochemical expression of desmoglein, and ultrastructural changes of desmosomes increased in length and number. No evidence for abnormalities in epithelial cell polarization, proliferation, or T-cell activation was found. CONCLUSIONS: This study strongly suggests a role played by alterations of cell-cell and cell-matrix interactions in the pathogenesis of epithelial dysplasia.

Antigens, Differentiation↗
PubMed1997

Cytokines modulate fibroblast phenotype and epithelial-stroma interactions in rat intestine.

BACKGROUND & AIMS: Homeostasis of the intestinal epithelium depends on interactions with the underlying connective tissue that may be altered during the pathogenesis of disease. The aim of this study was to establish whether fibroblast phenotype can influence morphogenesis and differentiation of the gut epithelium. METHODS: Permanently growing, nontumorigenic, homogenous fibroblast lines were established from postnatal rat intestinal mucosa. Their phenotypic characterization included their growth response to cytokines and expression of cytoskeletal and membrane markers, as well as expression of basement membrane components, laminin 1 and collagen IV. Their influence on epithelial growth, functional polarization, and morphogenesis was analyzed using coculture and tissue grafting of the fibroblast lines with fetal gut endoderm. RESULTS: Two intestinal fibroblast lines are described, one that supports normal intestinal morphogenesis and differentiation, and one that induces growth of fetal epithelial cells. Among the phenotypic differences between the two lines, the former differentiates into myofibroblasts in response to transforming growth factor beta1 and, in basal conditions, expresses twice as much laminin than the latter. The growth of the two lines is also affected differentially by transforming growth factor beta1 and interleukin 2. CONCLUSIONS: Cytokines, which are expressed in association with inflammation, regulate fibroblast differentiation. Fibroblasts may modify the function and organization of the overlying intestinal epithelium.

Animals↗
PubMed1997

In vitro effects of oxpentifylline on inflammatory cytokine release in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta, have been implicated as primary mediators of intestinal inflammation in inflammatory bowel disease. AIM: To investigate the in vitro effects of oxpentifylline (pentoxifylline; PTX; a phosphodiesterase inhibitor) on inflammatory cytokine production (1) by peripheral mononuclear cells (PBMCs) and (2) by inflamed intestinal mucosa cultures from patients with Crohn's disease and patients with ulcerative colitis. METHODS: PBMCs and mucosal biopsy specimens were cultured for 24 hours in the absence or presence of PTX (up to 100 micrograms/ml), and the secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 determined by enzyme linked immunosorbent assays (ELISAs). RESULTS: PTX inhibited the release of TNF-alpha by PBMCs from patients with inflammatory bowel disease and the secretion of TNF-alpha and IL-1 beta by organ cultures of inflamed mucosa from the same patients. Secretion of TNF-alpha by PBMCs was inhibited by about 50% at a PTX concentration of 25 micrograms/ml (IC50). PTX was equally potent in cultures from controls, patients with Crohn's disease, and those with ulcerative colitis. The concentrations of IL-6 and IL-8 were not significantly modified in PBMCs, but IL-6 increased slightly in organ culture supernatants. CONCLUSIONS: PTX or more potent related compounds may represent a new family of cytokine inhibitors, potentially interesting for treatment of inflammatory bowel disease.

Adult↗
PubMed1997

Mesenchyme-mediated effects of retinoic acid during rat intestinal development.

In previous experiments we showed that intestinal development was dependent upon epithelial-mesenchymal cell interactions. The aim of this study was to investigate the possible role of retinoic acid (RA), a morphogenetic and differentiating agent, on the gut epithelial-mesenchymal unit. For this purpose we first analyzed the effects of a physiological dose of RA on 14-day fetal rat intestine using short-term organ culture experiments, or long-term grafts under the skin of nude mice. In these conditions, RA accelerated villus outgrowth and epithelial cell differentiation as assessed by the onset of lactase expression, and it also stimulated muscle and crypt formation. In order to analyze potential effects of RA mediated by mesenchymal cells, we isolated and characterized gut mucosa mesenchyme-derived cell cultures (mesenchyme-derived intestinal cell lines, MIC). These cells were shown to express mRNAs for retinoid binding proteins similar to those expressed in situ in the intestinal mesenchyme. MIC cells co-cultured with 14-day intestinal endoderms promoted endodermal cell adhesion and growth, and the addition of exogeneous RA enhanced epithelial cell polarization and differentiation assessed by cytokeratin and lactase immunostaining. Such a differentiating effect of RA was not observed on endodermal cells when cultured without a mesenchymal feeder layer or maintained in conditioned medium from RA-treated MIC cells. In the co-cultures, immunostaining of laminin and collagen IV with polyclonal antibodies, as well as alpha1 and beta1 laminin chains mRNAs (analyzed by RT-PCR) increased concurrently with the RA-enhanced differentiation of epithelial cells. It is worth noting that this stimulation by RA was also obvious on the mesenchymal cells cultured alone. These results show that RA plays a role in intestinal morphogenesis and differentiation. In addition, they indicate that RA acts on the mesenchymal cell phenotype and suggest that RA may modify the mesenchymal-epithelial cell interactions during intestinal development.

Animals↗
PubMed1997

Changing intestinal connective tissue interactions alters homeobox gene expression in epithelial cells.

In segmented organs, homeobox genes are involved in axial patterning and cell identity. Much less is known about their role in non-segmented endoderm derivatives such as the digestive epithelium. Using a xenograft model of fetal intestinal anlagen implanted under the skin of nude mice, we have investigated whether the expression of five homeobox genes (HoxA-4, HoxA-9, HoxC-8, Cdx-1 and Cdx-2) is modified when intestinal epithelium undergoes normal development or displays heterodifferentiation in association with heterotopic mesenchyme. In homotypic associations of fetal endoderm and mesenchyme that recapitulate normal development, the overall pattern of homeobox gene expression was maintained: HoxA-9 and HoxC-8 were the highest in the colon and ileum, respectively, and HoxA-4 was expressed all along the intestine; Cdx-1 and Cdx-2 exhibited an increasing gradient of expression from small intestine to colon. Yet, grafting per se caused a faint upregulation of HoxA-9 and HoxC-8 in small intestinal regions in which these genes are not normally expressed, while the endoderm-mesenchyme dissociation-association step provoked a decay of Cdx-1 in the colon. In heterotopic associations of colonic endoderm with small intestinal mesenchyme, the colonic epithelium exhibited heterodifferentiation to a small intestinal-like phenotype. In this case, we observed a decay of HoxA-9 expression and an upregulation of HoxC-8. Additionally, heterodifferentiation of the colonic epithelium was accompanied by a downregulation of Cdx-1 and Cdx-2 to a level similar to that found in the normal small intestine. To demonstrate that mesenchyme-derived cells can influence Cdx-1 and Cdx-2 expression in the bowel epithelium, fetal jejunal endoderm was associated with intestinal fibroblastic cell lines that either support small intestinal-like or colonic-like morphogenesis. A lower expression of both homeobox genes was shown in grafts presenting the small intestinal phenotype than in those showing glandular colonic-like differentiation. Taken together, these results suggest that homeobox genes participate in the control of the positional information and/or cell differentiation in the intestinal epithelium. They also indicate that the level of Cdx-1 and Cdx-2 homeobox gene expression is influenced by epithelial-mesenchymal cell interactions in the intestinal mucosa.

Animals↗
PubMed1996

Human fetal enterocytes in vitro: modulation of the phenotype by extracellular matrix.

The differentiation of small intestinal epithelial cells may require stimulation by microenvironmental factors in vivo. In this study, the effects of mesenchymal and luminal elements in nonmalignant epithelia] cells isolated from the human fetus were studied in vitro. Enterocytes from the human fetus were cultured and microenvironmental factors were added in stages, each stage more closely approximating the microenvironment in vivo. Four stages were examined: epithelial cells derived on plastic from intestinal culture and grown as a cell clone, the same cells grown on connective tissue support, primary epithelial explants grown on fibroblasts with a laminin base, and primary epithelial explants grown on fibroblasts and laminin with n-butyrate added to the incubation medium. The epithelial cell clone dedifferentiated when grown on plastic; however, the cells expressed cytokeratins and villin as evidence of their epithelial cell origin. Human connective tissue matrix from Engelbreth-Holm-Swarm sarcoma cells (Matrigel) modulated their phenotype: alkaline phosphatase activity increased, microvilli developed on their apical surface, and the profile of insulin-like growth factor binding proteins resembled that secreted by differentiated enterocytes. Epithelial cells taken directly from the human fetus as primary cultures and grown as explants on fibroblasts and laminin expressed greater specific enzyme activities in brush border membrane fractions than the cell clone. These activities were enhanced by the luminal molecule sodium butyrate. Thus the sequential addition of connective tissue and luminal molecules to nonmalignant epithelia] cells in vitro induces a spectrum of changes in the epithelial cell phenotype toward full differentiation.

Alkaline Phosphatase↗
PubMed1996

Developmental expression of laminin-5 and HD1 in the intestine: epithelial to mesenchymal shift for the laminin gamma-2 chain subunit deposition.

We report the expression pattern of hemidesmosome-associated proteins laminin-5, composed of alpha 3 beta 3 gamma 2 chains, and HD1 in the developing mouse and human intestine, an organ in which variations in structure and function parallel morphogenesis and differentiation. Immunocytochemistry analysis revealed the coexpression of laminin-5 and HD1 at the basal pole of differentiating epithelial cells. Distinct noticeable variations occurring in the location of laminin alpha 3 chain in development of mouse gut were stressed by the reverse transcriptase-polymerase chain reaction data. A peculiar finding was also the location of laminin gamma 2 chain in the intestinal muscle coat. The cellular origin of laminin gamma 2 chain was examined by immunocytochemistry on interspecies hybrid intestines with specific antibodies recognizing mouse antigens. Complementary and sequential production of laminin gamma 2 chain was observed, by epithelial cells as establishment of the basement membrane occurs and by mesenchymal cells in the more differentiated organ. These results support the concept of mesenchymal involvement in deposition of basement membrane molecules, a crucial process for intestinal differentiation. Taken together these data provide the first evidence for the coexpression of hemidesmosome-associated proteins in the gut, a non-stratified tissue.

Aging↗
PubMed1996

Inhibition of laminin alpha 1-chain expression leads to alteration of basement membrane assembly and cell differentiation.

The expression of the constituent alpha 1 chain of laminin-1, a major component of basement membranes, is markedly regulated during development and differentiation. We have designed an antisense RNA strategy to analyze the direct involvement of the alpha 1 chain in laminin assembly, basement membrane formation, and cell differentiation. We report that the absence of alpha 1-chain expression, resulting from the stable transfection of the human colonic cancer Caco2 cells with an eukaryotic expression vector comprising a cDNA fragment of the alpha 1 chain inserted in an antisense orientation, led to (a) an incorrect secretion of the two other constituent chains of laminin-1, the beta 1/gamma 1 chains, (b) the lack of basement membrane assembly when Caco2-deficient cells were cultured on top of fibroblasts, assessed by the absence of collagen IV and nidogen deposition, and (c) changes in the structural polarity of cells accompanied by the inhibition of an apical digestive enzyme, sucrase-isomaltase. The results demonstrate that the alpha 1 chain is required for secretion of laminin-1 and for the assembly of basement membrane network. Furthermore, expression of the laminin alpha 1-chain gene may be a regulatory element in determining cell differentiation.

Base Sequence↗
PubMed1995

Extracellular matrix components in intestinal development.

Intestinal morphogenesis and differentiation are dependent on heterotypic cell interactions between embryonic epithelial cells (endoderm) and stromal cells (mesenchyme). Extracellular matrix molecules represent attractive candidates for regulators of these interactions. The structural and functional diversity of the extracellular matrix as intestinal development proceeds is demonstrated by 1) spatio-temporal specific expression of the classically described constituents, 2) the finding of laminin and collagen IV variants, 3) changes in the ratio of individual constituent chains, and 4) a stage-specific regulation of basement membrane molecule production, in particular by glucocorticoids. The orientation/assembly of these extracellular matrix molecules could direct precise cellular functions through interactions via integrin molecules. The involvement of extracellular matrix, and in particular basement membrane molecules in heterotypic cell interactions leading to epithelial cell differentiation, has been highlighted by the use of experimental models such as cocultures, hybrid intestines and antisense approaches. These models allowed us to conclude that a correct elaboration and assembly of the basement membrane, following close contacts between epithelial and fibroblastic cells, is necessary for the expression of differentiation markers such as digestive enzymes.

Animals↗
PubMed1995

Intractable diarrhea of infancy with epithelial and basement membrane abnormalities.

We describe a form of intractable diarrhea in six children (four girls) with similar clinical histories and identical histopathologic features. The children had watery diarrhea of neonatal onset requiring total parenteral nutrition. Two had siblings who had died of diarrhea in the first year of life; two others are sisters. Repeated duodenal or jejunal biopsies revealed villous atrophy with normal or hyperplastic and regenerative cryptae, normal cellularity of the lamina mesenterii propria, and no signs of T-cell activation. The main histologic features are epithelial dysplasia with focal crowding and disorganization of the surface enterocytes, pseudocystic formation of the glands, and abnormal regenerative cryptae. The basement membrane components were studied with polyclonal antibodies on frozen specimens, and were compared with biopsy specimens from patients with celiac disease or autoimmune enteropathy. Relative to the control subjects, there was faint and irregular deposition of laminin at the epithelium-lamina mesenterii propria interface, whereas deposits of heparan sulfate proteoglycan were large and lamellar. The primary or secondary nature of these modifications of the basement membrane remains to be determined, but the modifications might be related to epithelial abnormalities and to the severity of this neonatal diarrhea, which resisted all treatment and necessitated permanent total parenteral nutrition.

Basement Membrane↗
PubMed1994

Differential expression of laminin isoforms and alpha 6-beta 4 integrin subunits in the developing human and mouse intestine.

The intestinal tissue is characterized by important morphogenetic movements during development as well as by a continuous dynamic crypt to villus epithelial cell migration leading to differentiation of specialized cells. In this study, we have examined the spatio-temporal distribution of laminin A and M chains as well as of alpha 6 and beta 4 integrin subunits in adult and developing human and mouse intestine by indirect immunofluorescence. Selective expression of the constituent polypeptides of laminin isoforms (A and M chains) was demonstrated. In the mature human intestine, A and M chains were found to be complementary, the M chain being restricted to the base of crypts and the A chain lining the villus basement membrane. In the developing human intestine, M chain expression was delayed as compared to that of A chain; as soon as the M chain was visualized, it exhibited the typical localization in the crypt basement membrane. A somewhat different situation was found in the adult mouse intestine, since both M and A chains were found in the crypts. During mouse intestinal development the delayed expression of the M chain as compared to that of the A chain was also obvious. The absence of M chain expression in mutant dy mouse did not impair intestinal morphogenesis nor cell differentiation. The expression of alpha 6 and beta 4 subunits was not coordinated. In both species the alpha 6 expression preceded that of beta 4. Furthermore, while beta 4 staining in adult mouse intestine was detected at the basal surface of all cells lining the crypt-villus, that of alpha 6 was mainly confined to the crypt cell compartment. An overall similarity of location between alpha 6 integrin subunit and laminin A chain at the epithelial/stromal interface was noted. These data indicate that the spatial and temporal distribution of laminin variants in the developing intestine may be characteristic for each species and that interactions of laminin variants with particular receptors may be important for induction and/or maintenance of differentiated cells.

Adult↗
PubMed1994

Fetal endoderm primarily holds the temporal and positional information required for mammalian intestinal development.

In rodents, the intestinal tract progressively acquires a functional regionalization during postnatal development. Using lactase-phlorizin hydrolase as a marker, we have analyzed in a xenograft model the ontogenic potencies of fetal rat intestinal segments taken prior to endoderm cytodifferentiation. Segments from the presumptive proximal jejunum and distal ileum grafted in nude mice developed correct spatial and temporal patterns of lactase protein and mRNA expression, which reproduced the normal pre- and post-weaning conditions. Segments from the fetal colon showed a faint lactase immunostaining 8-10 d after transplantation in chick embryos but not in mice; it is consistent with the transient expression of this enzyme in the colon of rat neonates. Heterotopic cross-associations comprising endoderm and mesenchyme from the presumptive proximal jejunum and distal ileum developed as xenografts in nude mice, and they exhibited lactase mRNA and protein expression patterns that were typical of the origin of the endodermal moiety. Endoderm from the distal ileum also expressed a normal lactase pattern when it was associated to fetal skin fibroblasts, while the fibroblasts differentiated into muscle layers containing alpha-smooth-muscle actin. Noteworthy, associations comprising colon endoderm and small intestinal mesenchyme showed a typical small intestinal morphology and expressed the digestive enzyme sucrase-isomaltase normally absent in the colon. However, in heterologous associations comprising lung or stomach endoderm and small intestinal mesenchyme, the epithelial compartment expressed markers in accordance to their tissue of origin but neither intestinal lactase nor sucrase-isomaltase. A thick intestinal muscle coat in which cells expressed alpha-smooth-muscle actin surrounded the grafts. The results demonstrate that: (a) the temporal and positional information needed for intestinal ontogeny up to the post-weaning stage results from an intrinsic program that is fixed in mammalian fetuses prior to endoderm cytodifferentiation; (b) this temporal and positional information is primarily carried by the endodermal moiety which is also able to change the fate of heterologous mesodermal cells to form intestinal mesenchyme; and (c) the small intestinal mesenchyme in turn may deliver instructive information as shown in association with colonic endoderm; yet this effect is not obvious with nonintestinal endoderms.

Aging↗