Sox4-Deficiency Syndrome in Mice Is an Animal Model for Common Trunk

Abstract

Embryonic mice lacking functional Sox4 transcription factor die from cardiac failure at embryonic day (ED) 14. Heart morphogenesis in these embryos was analyzed in hematoxylin-azophlochsin or immunohistochemically stained, 3-dimensionally reconstructed serial sections between ED12 and ED14. Although Sox4 is expressed in the endocardially derived tissue of both the outflow tract and atrioventricular canal, Sox4-deficient hearts only suffer from defective transformation of the endocardial ridges into semilunar valves and from lack of fusion of these ridges, usually resulting in common trunk, although the least affected hearts should be classified as having a large infundibular septal defect. The more serious cases are, in addition, characterized by an abnormal number and position of the semilunar valve-leaflet anlagen, a configuration of the ridges typical for transposition of the great arteries (with linear rather than spiral course of both ridges and posterior position of the pulmonary trunk at the level of the valve), and variable size of the aorta relative to the pulmonary trunk. The coronary arteries always originated from the aorta, irrespective of its position relative to the pulmonary trunk. The restriction of the malformations to the arterial pole implies that the interaction between the endocardially derived tissue of the outflow tract and the neural crest-derived myofibroblasts determines proper development of the arterial pole.

Molecular markers of cardiac endocardial cushion development

“…2K,L, 3K,L, 4K,L). Runx2 plays an important role in epithelial HMG-box transcription factor Ya et al, 1998 to mesenchymal transformation during tooth formation and in the development of osteoblasts, processes in which TGF␤ signaling has been implicated. Runx2 may be an downstream effector of TGF␤ signaling (Lee et al, 2000).…”

Sox-4 is a positive regulator of Hep3B and HepG2 cells' apoptosis induced by prostaglandin (PG)A2 and Δ12-PGJ2

“…Recent studies revealed that the mutation of Sox-4(Sox-4 -/-) in the embryo of mice leads to premature death at 14th embryonic days due to impaired development of the endocardial ridges (Schilham et al, 1996: Ya et al, 1998. In 1998, Southard-Smith et al reported that premature termination of Sox-10, a member of the Sox family, disrupted neural crest development due to apoptosis in Dom Hirschsprung mouse models.…”

“…Many Sox (SRY-HMG box containing) proteins are assumed to be involved in the regulation of developmental stages of several distinct tissues (Uwanogho et al, 1995: Schilham et al, 1998: Southard-Smith et al, 1998 and nervous system in mammals (Prior andWalter, 1996: Jay et al, 1997). Unlike other Sox family proteins, Sox-4, a transcription factor, contains serine-rich trans-activation domain in the C-terminus and is selectively expressed in brain, heart and testis of fetus mice (van de Wetering et al, 1993: Schilham et al, 1997.…”

Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma

“…This suggests that the SOX4 molecular activity during caracinogenesis is influenced by additional factors that are enriched in a tissuespecific manner. The requirement for SOX4 in a wide range of developmental processes (van De et al, 1993;Ya et al, 1998;Cheung et al, 2000) further argues for a synergy between SOX4 and tissue-selective partner proteins. Among the identified highly upregulated genes in intrahepatic liver tumors, SOX4 was an attractive candidate for further investigation.…”