Mesenchymal Expression of Tbx4 Gene is Not Altered in Adriamycin Mouse Model

Overview

Journal Pediatr Surg Int

Specialties General Surgery
Pediatrics

Date 2010 Feb 26

PMID 20182749

Citations 4

Authors

Piotr Hajduk

Paula Murphy

Prem Puri

Affiliations

Soon will be listed here.

Abstract

Purpose: The Adriamycin mouse model (AMM) is a reproducible teratogenic model of esophageal atresia/tracheo-esophageal fistula (EA/TEF). Tbx4 is a member of the T-box family of transcription factor genes, which is reported to play a key role in separation of the respiratory tract and the esophagus. Up-regulation of Tbx4 is reported to cause TEF in the chick. Optical projection tomography (OPT) is a technique that allows three-dimensional (3D) imaging of gene expression in small tissue specimens in an anatomical context. The aim of this study was to investigate the temporo-spatial expression of Tbx4 during the critical period of separation of the trachea and esophagus in normal and Adriamycin treated embryos using OPT.

Materials And Methods: Time-mated CBA/Ca mice received intraperitoneal injections of Adriamycin (6 mg/kg) or saline on days 7 and 8 of gestation. Embryos were harvested on days 9-12, stained following whole mount in situ hybridization with labeled RNA probes to detect Tbx4 transcripts (n = 5 for each treatment/day of gestation). Immunolocalization with the endoderm marker Hnf3beta was used to visualize morphology. Embryos were scanned by OPT to obtain 3D representations of gene expression domains. Animal licence no. B100/4106.

Results: OPT elegantly revealed Tbx4 gene expression in both controls and in the disorganized pulmonary mesenchyme in the treated embryos. Although characteristic morphological abnormalities were observed in Adriamycin treated embryos, there was no significant difference in Tbx4 transcript distribution around lung primordia in comparison with control embryos.

Conclusion: Although previously reported morphological abnormalities of notochord and esophagus were observed in AMM, Tbx4 gene expression was unaltered, suggesting that esophageal anomalies can occur in the presence of normal Tbx4 gene expression in this model.

Citing Articles

Identification and Functional Evaluation of a Novel Mutation Underlies Small Patella Syndrome.

Li P, Lan W, Li J, Zhang Y, Xiong Q, Ye J Int J Mol Sci. 2022; 23(4).

PMID: 35216193 PMC: 8875086. DOI: 10.3390/ijms23042075.

Altered Tbx1 gene expression is associated with abnormal oesophageal development in the adriamycin mouse model of oesophageal atresia/tracheo-oesophageal fistula.

Mc Laughlin D, Murphy P, Puri P Pediatr Surg Int. 2013; 30(2):143-9.

PMID: 24356861 DOI: 10.1007/s00383-013-3455-9.

Design and implementation of a custom built optical projection tomography system.

Wong M, Dazai J, Walls J, Gale N, Henkelman R PLoS One. 2013; 8(9):e73491.

PMID: 24023880 PMC: 3762719. DOI: 10.1371/journal.pone.0073491.

Adriamycin-Induced Models of VACTERL Association.

Mc Laughlin D, Hajduk P, Murphy P, Puri P Mol Syndromol. 2013; 4(1-2):46-62.

PMID: 23653576 PMC: 3638781. DOI: 10.1159/000345579.

References

Ang S, Wierda A, Wong D, STEVENS K, Cascio S, Rossant J . The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development. 1993; 119(4):1301-15. DOI: 10.1242/dev.119.4.1301. View

Maeda Y, Dave V, Whitsett J . Transcriptional control of lung morphogenesis. Physiol Rev. 2007; 87(1):219-44. DOI: 10.1152/physrev.00028.2006. View

Summerhurst K, Stark M, Sharpe J, Davidson D, Murphy P . 3D representation of Wnt and Frizzled gene expression patterns in the mouse embryo at embryonic day 11.5 (Ts19). Gene Expr Patterns. 2008; 8(5):331-48. PMC: 2452985. DOI: 10.1016/j.gep.2008.01.007. View

Quan L, Smith D . The VATER association. Vertebral defects, Anal atresia, T-E fistula with esophageal atresia, Radial and Renal dysplasia: a spectrum of associated defects. J Pediatr. 1973; 82(1):104-7. DOI: 10.1016/s0022-3476(73)80024-1. View

Diez-Pardo J, Baoquan Q, Navarro C, Tovar J . A new rodent experimental model of esophageal atresia and tracheoesophageal fistula: preliminary report. J Pediatr Surg. 1996; 31(4):498-502. DOI: 10.1016/s0022-3468(96)90482-0. View

Sharpe J, Ahlgren U, Perry P, Hill B, Ross A, Hecksher-Sorensen J . Optical projection tomography as a tool for 3D microscopy and gene expression studies. Science. 2002; 296(5567):541-5. DOI: 10.1126/science.1068206. View

Litingtung Y, Lei L, Westphal H, Chiang C . Sonic hedgehog is essential to foregut development. Nat Genet. 1998; 20(1):58-61. DOI: 10.1038/1717. View

CHAPMAN D, Garvey N, Hancock S, Alexiou M, Agulnik S, Bollag R . Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. Dev Dyn. 1996; 206(4):379-90. DOI: 10.1002/(SICI)1097-0177(199608)206:4<379::AID-AJA4>3.0.CO;2-F. View

Costa R, Kalinichenko V, Lim L . Transcription factors in mouse lung development and function. Am J Physiol Lung Cell Mol Physiol. 2001; 280(5):L823-38. DOI: 10.1152/ajplung.2001.280.5.L823. View

10.

Khoury M, Cordero J, GREENBERG F, James L, Erickson J . A population study of the VACTERL association: evidence for its etiologic heterogeneity. Pediatrics. 1983; 71(5):815-20. View

11.

Sakiyama J, Yamagishi A, Kuroiwa A . Tbx4-Fgf10 system controls lung bud formation during chicken embryonic development. Development. 2003; 130(7):1225-34. DOI: 10.1242/dev.00345. View

12.

Ioannides A, Chaudhry B, Henderson D, Spitz L, Copp A . Dorsoventral patterning in oesophageal atresia with tracheo-oesophageal fistula: Evidence from a new mouse model. J Pediatr Surg. 2002; 37(2):185-91. DOI: 10.1053/jpsu.2002.30252. View

13.

Naito Y, Kimura T, Aramaki M, Izumi K, Okada Y, Suzuki H . Caudal regression and tracheoesophageal malformation induced by adriamycin: a novel chick model of VATER association. Pediatr Res. 2009; 65(6):607-12. DOI: 10.1203/PDR.0b013e31819e7317. View

14.

Ang S, Rossant J . HNF-3 beta is essential for node and notochord formation in mouse development. Cell. 1994; 78(4):561-74. DOI: 10.1016/0092-8674(94)90522-3. View

15.

Hajduk P, Murphy P, Puri P . Fgf10 gene expression is delayed in the embryonic lung mesenchyme in the adriamycin mouse model. Pediatr Surg Int. 2009; 26(1):23-7. DOI: 10.1007/s00383-009-2519-3. View

16.

Sato H, Murphy P, Giles S, Bannigan J, Takayasu H, Puri P . Visualizing expression patterns of Shh and Foxf1 genes in the foregut and lung buds by optical projection tomography. Pediatr Surg Int. 2007; 24(1):3-11. DOI: 10.1007/s00383-007-2036-1. View

17.

Que J, Choi M, Ziel J, Klingensmith J, Hogan B . Morphogenesis of the trachea and esophagus: current players and new roles for noggin and Bmps. Differentiation. 2006; 74(7):422-37. DOI: 10.1111/j.1432-0436.2006.00096.x. View

18.

Temtamy S, Miller J . Extending the scope of the VATER association: definition of the VATER syndrome. J Pediatr. 1974; 85(3):345-9. DOI: 10.1016/s0022-3476(74)80113-7. View

19.

Merei J, Hutson J . Embryogenesis of tracheo esophageal anomalies: a review. Pediatr Surg Int. 2002; 18(5-6):319-26. DOI: 10.1007/s00383-002-0751-1. View

20.

Lioubinski O, Alonso M, Alvarez Y, Vendrell V, Garrosa M, Murphy P . FGF signalling controls expression of vomeronasal receptors during embryogenesis. Mech Dev. 2005; 123(1):17-23. DOI: 10.1016/j.mod.2005.10.004. View