Temporal and spatial expression of caudal-type homeobox gene-1 in the development of anorectal malformations in rat embryos

Zhang, Tao; Bai, Yu; Zhang, Dan; Zhang, Shi Wei; Wang, Da Jia; Jia, Hui; Yuan, Zheng Wei; Wang, Wei Lin

doi:10.1016/j.jpedsurg.2008.10.002

Cited by 7 publications

(11 citation statements)

References 27 publications

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“…Furthermore, the dynamic expression pattern of CDX1 along the developing has been proposed that CDX1 is involved in both the caudal region of the embryo and AP patterning17,18. On the other hand, it was reported that downregulation of CDX1 at the time of cloacal separation into rectum and urethra might be related to the development of ARMs19. Indeed, evidences from these studies have strengthened our observation that CDX1 plays an important role in human anorectal development and the pathogenesis of ARMs.…”

Section: Introductionsupporting

confidence: 69%

Mutations and Down-Regulation of CDX1 in Children with Anorectal Malformations

Zhang¹,

Tang²,

Wang³

et al. 2013

Int. J. Med. Sci.

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Background: Anorectal malformations (ARMs) represent a variety of congenital disorders that involve abnormal termination of the anorectum. This study was to reveal relation between CDX1 and human ARMs phenotypes.Methods: 108 Chinese patients and 120 Chinese controls were included in this study. We analyzed the relation between two by PCR, qRT-PCR, western blot and immunofluorescence.Results: Four heterozygous mutations in CDX1 gene were identified in ARMs patients (3.7%, 4/108), no found in controls. CDX1 protein expression was significantly decreased in the ARMs compared with the control anorectum. All samples analyzed in ARMs group exhibited down-regulated CDX1 mRNA expression in comparison to matched normal group, demonstrated significant differences statistically.Conclusion: The findings represented the relation between CDX1 mutations and CDX1 genotype. Furthermore, it was suggested that the downregulation of CDX1 might be related to the development of ARMs.

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Section: Introductionsupporting

confidence: 69%

Mutations and Down-Regulation of CDX1 in Children with Anorectal Malformations

Zhang¹,

Tang²,

Wang³

et al. 2013

Int. J. Med. Sci.

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“…Our earlier studies on the spatiotemporal expression pattern of Cdx1 and Cdx2 in rat embryos suggested that the downregulation of Cdx1 and Cdx2 at the time of cloaca separation into rectum and urethra is related to the development of ARM [Zhang et al, 2009;Tang et al, 2014]. Cdx1 overexpression mice manifest defects in the female urogenital system [Gaunt and Paul, 2011].…”

Section: Discussionmentioning

confidence: 99%

“…About 80% of the offspring of these rats have ARMs ranging from a simple, covered anus to rectourethral fistulae [Hirai and Kuwabara, 1990], which closely resemble those seen in neonates with ARMs, so this is an ideal animal model for investigating ARM embryogenesis. ETU-induced ARM in rat embryos has been previously used to study the morphological changes of ARM by our group and others [Qi et al, 2002;Bai et al, 2004;Mandhan et al, 2006;Zhang et al, 2009].…”

Section: Discussionmentioning

confidence: 99%

“…The Cdx (caudal-type homeobox) genes show a highly restricted expression pattern at the onset of gastrulation, suggesting their involvement in the formation of the digestive tract [McGinnis and Krumlauf, 1992;Bonner et al, 1995;Silberg et al, 2000]. Our earlier studies on the spatiotemporal expression pattern of Cdx1 and Cdx2 in the rat embryo suggested that the downregulation of Cdx1 and Cdx2 at the time of separation of the cloaca into rectum and urethra is related to the development of ARM [Zhang et al, 2009;Tang et al, 2014]. Cdx1 , Cdx2 and Cdx4 are expressed in the developing hindgut endoderm [Beck, 2002].…”

Section: Introductionmentioning

confidence: 99%

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Spatiotemporal Expression of <b><i>Cdx4</i></b> in the Developing Anorectum of Rat Embryos with Ethylenethiourea-Induced Anorectal Malformations

Tang

Zhang

Wang

et al. 2014

Cells Tissues Organs

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Purpose: The aim of this study was to determine the expression of Cdx4 (caudal-type homeobox gene-4) during anorectal development in normal and ethylenethiourea (ETU)-induced anorectal malformation (ARM) embryos with a view to establishing the possible role of Cdx4 in ARM pathogenesis. Materials and Methods: ARM was induced by ETU on the 10th gestational day (GD10) in rat embryos. Cesarean deliveries were then performed to harvest the embryos. Spatiotemporal expression of Cdx4 was evaluated in normal rat embryos (n = 354) and ARM embryos (n = 378) from GD13 to GD16. Results: Immunohistochemical staining and immunofluorescencerevealed that, in normal embryos, Cdx4 expression was extensively detected on the epithelium of the cloaca on GD13. On GD14, the Cdx4-positive cells were intensively detected on the hindgut. On GD15, the anal membrane was constantly immunoreactive to Cdx4. On GD16, Cdx4-labeled cells were observed on the epithelium of the anus. In the ARM embryos, the epithelium of the cloaca, urorectal septum (URS) and anorectum was negative or faint for Cdx4. In the normal embryo group, Cdx4 protein and mRNA expression showed time-dependent changes in the developing hindgut from GD13 to GD16 on Western blot and real-time reverse transcription plus polymerase chain reaction. Once the URS divided the cloaca into the primitive rectum and urogenital sinus (UGS) on GD15, Cdx4 expression began to decrease. In addition, the expression level of Cdx4 in the ARM group from GD13 to GD15 was significantly lower than that in the normal group (p < 0.05). Conclusions: In ARM embryos, an imbalance in the spatiotemporal expression of Cdx4 was noted during anorectal morphogenesis from GD13 to GD16. This suggests that ETU may cause downregulation of Cdx4 expression. Downregulation of Cdx4 at the time of cloacal separation into the primitive rectum and UGS might thus be related to the development of ARM.

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“…A role for Gdf11 and its associated pro-protein convertase Pcsk5 has also been suggested, as inactivating the latter causes the VACTERL-like phenotype (Szumska et al, 2008), which comprises vertebral and ano-rectal anomalies. Recently, ano-rectal malformations induced by ethylenethiourea in rat embryos were reported to be accompanied by downregulation of Cdx1 (Zhang et al, 2009).…”

Section: Introductionmentioning

confidence: 99%