Abstract
Background. The objectives of this study were to determine the spatiotemporal distribution of human caudal-type homeobox proteins CDX1, CDX2 and CDX4 during development of the hindgut and anorectum in the embryo and to explore the possible roles of CDX genes during morphogenesis of the hindgut and anorectum.Methods. Embryos (89) were cut into sections serially and sagittally. From gestation weeks 4–9, CDX1, CDX2 and CDX4 proteins were detected on the caudal midline by immunohistochemical staining.Results. During week 4, extensive immunoreactivity of CDX1, CDX2 and CDX4 was detected in the dorsal urorectal septum, urogenital sinus and hindgut. From weeks 5–7, CDX1-, CDX2- and CDX4- positive cells were detected mainly in the mesenchyme of the urorectal septum and hindgut. The levels of CDX2 and CDX4 immunoreactivity were lower compared to CDX1. During weeks 8 and 9, the anorectal epithelium stained positive for CDX1 and CDX4, and the anal epithelium was positive for CDX2.Conclusions. The CDX proteins are constantly distributed during development of the hindgut and anorectum and exhibit overlapping distribution patterns in the cloaca/hindgut, suggesting they are important in the morphogenesis of the human hindgut and anorectum. CDX genes might be involved in development of the anorectal epithelium after the rectum has separated from the urorectal septum.
Highlights
Anorectal malformations (ARMs) are among the most common human congenital anomalies, occurring in approximately 1/5,000–1/1,500 live births (Van der Putte, 1986), with adverse influences on patient quality of life (Peña et al, 1998; Bai et al, 2000; Levitt & Peña, 2005)
cloacal membrane (CM) and urogenital sinus (UGS) were negative for CDX1, CDX2 and CDX4
The results of this study suggested CDX1, CDX2 and CDX4 were active in the urorectal septum (URS) during separation of the cloaca from gestation weeks 4–7, but their distribution level decreased after the anorectum and UGS opened to the amniotic cavity in week 8
Summary
Anorectal malformations (ARMs) are among the most common human congenital anomalies, occurring in approximately 1/5,000–1/1,500 live births (Van der Putte, 1986), with adverse influences on patient quality of life (Peña et al, 1998; Bai et al, 2000; Levitt & Peña, 2005). Earlier studies on the spatiotemporal expression patterns of Cdx, Cdx and Cdx in rat embryo suggested downregulation of these genes during separation of the cloaca into the rectum and urethra was related to ARM development (Zhang et al, 2009; Tang et al, 2014a; Tang et al, 2014b). Cdx2−/− mice displayed severe hindgut abnormalities with failure of colon development and complete terminal blockage (Gao, White & Kaestner, 2009), and Cdx2+/−; Cdx4−/− mice manifested cloacal septation and anorectal defects, including imperforate anus (Van de Ven et al, 2011) Together these results suggest Cdx genes are related to anorectal morphogenesis in animal models. The objectives of this study were to determine the spatiotemporal distribution of human caudal-type homeobox proteins CDX1, CDX2 and CDX4 during development of the hindgut and anorectum in the embryo and to explore the possible roles of CDX genes during morphogenesis of the hindgut and anorectum. CDX genes might be involved in development of the anorectal epithelium after the rectum has separated from the urorectal septum
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