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

1997 ◽  
Vol 110 (11) ◽  
pp. 1317-1324 ◽  
Author(s):  
I. Duluc ◽  
O. Lorentz ◽  
C. Fritsch ◽  
C. Leberquier ◽  
M. Kedinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Intestinal Epithelium ◽  
Normal Development ◽  
Homeobox Genes ◽  
Xenograft Model ◽  
Homeobox Gene ◽  
Mesenchymal Cell ◽  
Colonic Epithelium ◽  
Small Intestinal

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.

scholarly journals A low-temperature method for the isolation of small-intestinal epithelium along the crypt-villus axis

1991 ◽  
Vol 280 (2) ◽  
pp. 331-334 ◽  
Author(s):  
N Flint ◽  
F L Cove ◽  
G S Evans
Keyword(s):  
Small Intestine ◽  
Low Temperature ◽  
Intestinal Epithelium ◽  
Sequential Fractionation ◽  
Potential Value ◽  
Temperature Method ◽  
Small Intestinal ◽  
The Comparative Study ◽  
Cell Phenotypes ◽  
Proliferative Cell

A variety of enzymic and non-enzymic methods to isolate epithelium from the small intestine have been previously published. Sequential fractionation of cells from the villus to the crypt has been reported in some of these papers, which allows the comparative study of terminally differentiated and proliferative cell phenotypes. However, these methods often involve the incubation of tissues at 37 degrees C, which may affect the structural and biochemical integrity of the cells. We have developed a rapid low-temperature (4 degrees C) method for isolating purified populations of crypt and villus cells from mouse and rat intestines. The fractionated cells have been partially characterized, and the potential value of the procedure has been indicated by the ability to analyse the comparative protein and mRNA expression along the crypt-villus axis.

Comprehensive Analysis of Homeobox Gene Expression in Hodgkin Lymphoma Cell Lines Reveals Similarities to Prostate Carcinoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 966-966
Author(s):  
Stefan Nagel ◽  
Christof Burek ◽  
Hilmar Quentmeier ◽  
Corinna Meyer ◽  
Andreas Rosenwald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Prostate Carcinoma ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Cell Cycle Regulators ◽  
Rt Pcr

Abstract Homeobox genes code for transcription factors with essential regulatory impact on cellular processes during embryogenesis and in the adult. Increasingly, members of the circa 200 gene strong family are emerging as major oncogenic players, prompting our investigation into possible homeobox gene dysregulation in Hodgkin lymphoma (HL) in which no recurrent oncogene involvement has been known. Accordingly, we screened 6 well characterized HL cell lines (HDLM-2, KM-H2, L-1236, L-428, L-540, SUP-HD1) and 3 non-Hodgkin lymphoma (NHL) cell lines (RC-K8, RI-1, SC-1) for homeobox gene expression using Affymetrix U133-2.0 whole-genome oligonucleotide microarrays. Of 15 candidate genes thus shown to reveal HL-specific expression patterns, 5 homeobox genes were shortlisted as potentially key dysregulatory targets in HL after additional RT-PCR expression analysis relative to controls. While 3/5 homeobox genes were upregulated in HL (HOXB9, HOXC8, HLXB9), 2/5 were downregulated (BOB1, PAX5). Furthermore, cloning and sequencing RT-PCR products obtained with degenerate primers recognizing conserved homeobox motifs confirmed the predominant expression of HOXB9 in HL cells. However, fluorescence in situ hybridization (FISH) analysis of the HOXB locus (at 17q21) revealed no cytogenetic aberrations, indicating that its activation is conducted non-chromosomally in HL cells. Surprisingly, known target genes of HOXB9 and HOXC8 remained unperturbed, implying novel downstream effector pathways in HL cells. Antisense oligos directed against HOXB9 and forced expression experiments using cloned full length HOXB9 cDNA indicated its involvement in both proliferation and apoptosis. Cell cycle regulators BTG1, BTG2 and GEMININ have been described to interact with HOXB9 and may represent potential targets deserving investigation. We recently showed that HLXB9 promotes IL6 expression in HL cells in response to a constitutively active PI3K signalling pathway therein (Nagel et al., Leukemia19, 841–6, 2005). Our most recent data indicate that HLXB9 is also expressed in various NHL cell lines including anaplastic, diffuse and mediastinal large cell as well as follicular B-cell lymphomas while expression is notably absent from Burkitt, mantle cell and natural killer T-cell lymphomas reflecting their pathologic classification. Intriguingly, our data highlight unexpected similarities between HL and prostate cancer cells which together uniquely overexpress HOXB9, HOXC8 and HLXB9 (or its close homolog GBX2). Additional genes expressed in prostate carcinoma (HOXB13, PRAC1, PRAC2) were detected in two HL cell lines (KM-H2 and L-428) suggesting further parallels may be revealed. Detection of downregulated B-cell differentiation factors BOB1 and PAX5 in our panel of HL cell lines validated this approach. Both factors were previously implicated in oncogenesis of HL lacking IGH rearrangements and other key B-cell characteristics. In summary, we identified a unique homeobox gene expression pattern involving HOXB9, HOXB13, HOXC8 and HLXB9 in HL cell lines resembling that of prostate carcinoma cells. Overexpressed HOXB9 contributes to proliferation and protects against apoptosis in HL cells potentially via interacting with cell cycle regulators BTG1/2 and/or GEMININ.

Pepsinogen gene transcription induced in heterologous epithelial-mesenchymal recombinations of chicken endoderms and glandular stomach mesenchyme

Development ◽  
1988 ◽  
Vol 103 (4) ◽  
pp. 725-731 ◽  
Author(s):  
K. Hayashi ◽  
S. Yasugi ◽  
T. Mizuno
Keyword(s):  
Small Intestine ◽  
Digestive Tract ◽  
Gene Transcription ◽  
Normal Development ◽  
De Novo ◽  
Glandular Stomach ◽  
Northern Hybridization ◽  
Marker Protein ◽  
Chicken Embryos ◽  
Small Intestinal

Proventricular (glandular stomach) mesenchyme of chicken embryos can induce endoderms of some parts of embryonic digestive tract to produce embryonic chicken pepsinogen (ECPg), a marker protein for the differentiation of embryonic proventricular epithelium. In the present study, we investigated the production of ECPg mRNA in the course of epithelial-mesenchymal interactions between endoderms of digestive tract and proventricular mesenchyme. ECPg mRNA was detected by Northern hybridization with ECPg cDNA as a probe. In normal development of the proventriculus, ECPg mRNA was first detected at day 7 of incubation, and it ceased to be produced by day 21. Embryonic esophagus, gizzard and small intestine did not contain ECPg mRNA. When 6-day esophagus, gizzard or proventricular endoderm was associated and cultured with 6-day proventricular mesenchyme, the recombinates formed proventricular-gland-like complex glands and produced ECPg mRNA in almost equal quantity. However, 6-day small intestinal or 3.5-day allantoic endoderm did not produce pepsinogen mRNA under the same conditions, though the recombinates formed complex glands. These results indicate that the proventricular mesenchyme can induce de novo transcription of ECPg gene in esophagus, proventricular and gizzard endoderms, and that ECPg gene in small intestinal and allantoic endoderms fails to react to the inducing signal.

scholarly journals Motoneuron fate specification revealed by patterned LIM homeobox gene expression in embryonic zebrafish

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4117-4125 ◽  
Author(s):  
B. Appel ◽  
V. Korzh ◽  
E. Glasgow ◽  
S. Thor ◽  
T. Edlund ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Gene Transcription ◽  
Cell Body ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Positional Information ◽  
Axonal Projection ◽  
Fate Specification ◽  
Genes Expression

In zebrafish, individual primary motoneurons can be uniquely identified by their characteristic cell body positions and axonal projection patterns. The fate of individual primary motoneurons remains plastic until just prior to axogenesis when they become committed to particular identities. We find that distinct primary motoneurons express particular combinations of LIM homeobox genes. Expression precedes axogenesis as well as commitment, suggesting that LIM homeobox genes may contribute to the specification of motoneuronal fates. By transplanting them to new spinal cord positions, we demonstrate that primary motoneurons can initiate a new program of LIM homeobox gene expression, as well as the morphological features appropriate for the new position. We conclude that the patterned distribution of different primary motoneuronal types within the zebrafish spinal cord follows the patterned expression of LIM homeobox genes, and that this reflects a highly resolved system of positional information controlling gene transcription.

315. HOMEOBOX GENES ARE DIFFERENTIALLY EXPRESSED IN PRIMARY VILLOUS AND EXTRAVILLOUS TROPHOBLAST CELL LINEAGES DURING EARLY PREGNANCY

2010 ◽  
Vol 22 (9) ◽  
pp. 115
Author(s):  
P. Murthi ◽  
N. A. Pathirage ◽  
R. Keogh ◽  
M. Cocquebert ◽  
N. Segond ◽  
...  
Keyword(s):  
Gene Expression ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Trophoblast Cell ◽  
Differentially Expressed ◽  
Extravillous Trophoblast ◽  
Mrna Levels ◽  
Placental Development ◽  
Cell Lineages

During human placental development trophoblast cells differentiate along either the villous cytotrophoblast (VCT) lineage to form the syncytiotrophoblast (ST) or the invasive extravillous cytotrophoblast (EVCT) lineage (1). Abnormalities in early differentiation processes are characteristic of poor placentation, which is associated with fetal growth restriction (FGR) and pre-eclampsia (PE), the major clinical complications of human pregnancy (2). A large family of homeobox gene transcription factors controls “cell-fate decisions” during development (3), but the expression profile and role of homeobox genes in the human trophoblast cell lineages is not well understood. The aim of the study was to determine homeobox gene expression in primary cultures of mononuclear VCT (2h) and EVCT (2 h) obtained from first trimester human chorionic villi of 8–12 weeks of gestation and in vitro differentiated ST (72 h) and invasive EVCT (48 h), respectively. The isolation and characterization of freshly isolated VCT, EVCT and in vitro differentiated ST and invasive EVCT were performed as described previously (1,4). The homeobox gene mRNA profile was performed using PCR arrays in a pooled sample of VCT and EVCT (n = 6 in each group) and further validated by real-time PCR. Homeobox gene expression studies revealed MSX2 mRNA levels were the highest in VCT (2 h) but undetectable in EVCT (2 h). Further comparisons of homeobox gene expression in in vitro differentiated ST to invasive EVCT showed marked increase in MSX2, DLX3, DLX4 and MEIS1 mRNA levels in ST, which are regulators of cellular differentiation in many studies. Homeobox genes HLX and HHEX, which are implicated in regulating cellular proliferation showed decreased mRNA levels in ST compared to invasive EVCT. Our results demonstrated several known placental and novel homeobox genes are differentially expressed in trophoblast cell lineages. Functional studies of these candidate genes will provide a better understanding of the molecular mechanisms of early placental development. (1) Tarrade et al. (2001) Lab Invest. 81, 1199–1211.(2) LokeYW and King A (1995) Cell Biology and Immunology, Cambridge ed.(3) J Cross et al. (2002) Recent Progress in Hormone Research 57: 221–234.(4) Handschuh et al. (2007) Placenta, 28, 175–184.

Homeobox genes and the vertebrate head

Development ◽  
1988 ◽  
Vol 103 (Supplement) ◽  
pp. 17-24 ◽  
Author(s):  
Peter W. H. Holland
Keyword(s):  
Gene Expression ◽  
Embryonic Development ◽  
Neural Crest ◽  
Spatial Patterns ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Developing Brain ◽  
Characteristic Sequence ◽  
Head Development ◽  
Experimental Analyses

Several Drosophila genes important in the control of embryonic development contain a characteristic sequence of DNA, known as the homeobox. Homeobox sequences are also present in a family of vertebrate genes, which may therefore have regulatory roles during vertebrate embryogenesis. In this article, data concerning the spatial patterns of vertebrate homeobox gene expression are discussed in relation to recent descriptive and experimental analyses of head development. It is concluded that the patterns of gene expression are consistent with homeobox genes having roles in anteroposterior positional specification within the developing brain and possibly the neural crest. The data are not clearly consistent with these genes having direct roles in controlling the patterns of cranial segmentation, although further studies may reveal whether vertebrate segments are units of developmental specification.

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