Position‐specific expression of Hox genes along the gastrointestinal tract

Abstract

Hox genes play a critical role in morphogenesis of the early embryo along the anteroposterior axis. In mammals, 39 Hox genes with extensive homology are organized into 13 paralogous groups, forming four clusters on four separate chromosomes. The genes within each cluster are arranged in a 3' to 5' direction and expressed in a temporally and spatially coordinated manner along the anteroposterior axis in the vertebrae, limbs and viscera, including the gastrointestinal tract, but little is known about their spatial expression in the adult gastrointestinal tract. We used the quantitative polymerase chain reaction (PCR) intercalater method with SYBR Green to quantify human Hox gene expression in the adult gastrointestinal tract tissue: esophagus, stomach, duodenum, jejunum, ileum, ileocecum, cecum, ascending colon, transverse colon, descending colon and rectum. Hox gene expression was normalized to glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) gene expression. The spatial expression pattern was analyzed by the multivariate method. The expression level of all 39 Hox genes could be measured in a reproducible manner. Genes with higher expression in the foregut-derived segments tended to have lower expression in hindgut-derived segments, whereas those with low expression in the former tended to have higher in the latter. Principal components analysis and permax analysis revealed a position-specific expression pattern of Hox genes along the anteroposterior axis of the adult gastrointestinal tract. The pattern recapitulates the expression pattern in the embryonic gastrointestinal tract. We suggest that Hox genes may play a pivotal role in the position-specific regenerative process of intestinal epithelial cells.

Evidence for a functional role of epigenetically regulated midclusterHOXBgenes in the development of Barrett esophagus

“…Of note, we found high expression levels of midcluster HOXB genes also in BE cases with no histological evidence of globet cells, in keeping with the notion that a pathological diagnosis of BE can be supported by both gastric and intestinal metaplasia (35). With regards to HOXB gene levels in normal gut epithelia, our data are in agreement with previous evidence that midcluster HOXB genes are less expressed in the esophagus than in posterior segments of the GI tract (21). However, the midcluster HOXB profile we found in human adult GI tissues does differ from that found in embryonic murine gut (22).…”

“…With the exception of markers of intestinal differentiation and CDXs (5,20), little is known about similarities in gene-expression patterns between BE and other normal gut epithelia. In addition only one study has looked at HOX expression levels in the human adult gut (21). We tested the expression of midcluster HOXB genes also in other normal gastrointestinal (GI) epithelia, such as stomach, duodenum, and colon ( Fig.…”

HOXA13 Promotes Cancer Cell Growth and Predicts Poor Survival of Patients with Esophageal Squamous Cell Carcinoma

“…Accordingly, Yahagi and colleagues (9) showed that HOX genes with high expression in the foregut had a propensity for low expression in the hindgut, whereas those with a low expression in the foregut tended to have high expression in the hindgut. Specifically, paralogue 13 (HOXA13, HOXB13, and HOXD13) had a tendency for high expression in the hindgut region and weak expression in the foregut including the esophagus.…”

Breaking the seals: Efficient mRNA detection from human archival paraffin-embedded tissue

“…Malfunctioning and dysregulation of these genes during development lead to innate deformities and malformations (Dolle et al 1993a;Mark et al 1997;Zakany et al 1997). Dysregulation of HOX genes in adult tissue has been directly linked with cancer and tumorigenesis Yahagi et al 2004;Grier et al 2005). Our understanding of the role of HOX genes has mostly relied on animal models and, therefore, remains limited in normal and diseased human tissues (Johnson 1914;Kluth et al 1995).…”