Requirement of a novel gene, Xin, in cardiac morphogenesis

Abstract

A novel gene, Xin, from chick (cXin) and mouse (mXin) embryonic hearts, may be required for cardiac morphogenesis and looping. Both cloned cDNAs have a single open reading frame, encoding proteins with 2,562 and 1,677 amino acids for cXin and mXin, respectively. The derived amino acid sequences share 46% similarity. The overall domain structures of the predicted cXin and mXin proteins, including proline-rich regions, 16 amino acid repeats, DNA-binding domains, SH3-binding motifs and nuclear localization signals, are highly conserved. Northern blot analyses detect a single message of 8.9 and 5.8 kilo base (kb) from both cardiac and skeletal muscle of chick and mouse, respectively. In situ hybridization reveals that the cXin gene is specifically expressed in cardiac progenitor cells of chick embryos as early as stage 8, prior to heart tube formation. cXin continues to be expressed in the myocardium of developing hearts. By stage 15, cXin expression is also detected in the myotomes of developing somites. Immunofluorescence microscopy reveals that the mXin protein is colocalized with N-cadherin and connexin-43 in the intercalated discs of adult mouse hearts. Incubation of stage 6 chick embryos with cXin antisense oligonucleotides results in abnormal cardiac morphogenesis and an alteration of cardiac looping. The myocardium of the affected hearts becomes thickened and tends to form multiple invaginations into the heart cavity. This abnormal cellular process may account in part for the abnormal looping. cXin expression can be induced by bone morphogenetic protein (BMP) in explants of anterior medial mesoendoderm from stage 6 chick embryos, a tissue that is normally non-cardiogenic. This induction occurs following the BMP-mediated induction of two cardiac-restricted transcription factors, Nkx2.5 and MEF2C. Furthermore, either MEF2C or Nkx2.5 can transactivate a luciferase reporter driven by the mXin promoter in mouse fibroblasts. These results suggest that Xin may participate in a BMP-Nkx2.5-MEF2C pathway to control cardiac morphogenesis and looping.

Proteomic Analyses of the Developing Chicken Cardiovascular System

“…Supervillin and Xin are important for organization of actin in cells, which fits nicely in the hypothesis that during stage HH30/31 and later stages massive muscle development takes place. Ankyrin3 is important for normal electrical activity in cardiomyocytes and ankyrins are essential for the development of excitable membrane domains in heart tissue .…”

“…Desmoplakin is important for cellular organization by stabilizing desmosomes and its presence is fundamental for proper development of the embryonic heart. 17 Literature confirms the expression of xin 14 and titin/connectin 18 in the chicken embryonic heart. In the present study, we show that these proteins differentiate among stages and tissues investigated.…”

“…Literature confirms the expression of xin and titin/connectin in the chicken embryonic heart. In the present study, we show that these proteins differentiate among stages and tissues investigated.…”

Target formation in muscle fibres indicates reinnervation – A proteomic study in muscle samples from peripheral neuropathies

“…A possible experimental approach may be co-culture of muscle cells with motor neurons in a 3D cell culture. 1,28,[66][67][68] Target-like fibres that might develop in this setting could then be examined with a multitude of techniques.…”

Cardiac Overexpression of XIN Prevents Dilated Cardiomyopathy Caused by TNNT2 ΔK210 Mutation

“…Additionally, its localization at adherens junctions of muscle cells and interaction with β-catenin, filaminC, and Mena/VASP imply a role in linking and transducing signals important for cardiac remodeling. Inactivation of Xin in chick embryos led to looping defects, abnormal beating behavior and edema (Wang et al, 1999), while Xin-deficient mice display myopathy, impaired contractility, and attenuated muscle repair (Al-Sajee et al, 2015), which indicating a crucial role in heart development and cardiac disease. Moreover, it has been observed that Xin may participate in a BMP-Nkx2.5-MEF2C pathway and promote the expression of ventricular myosin heavy chain (vMHC) gene to participate in cardiogenesis regulation (Wang et al, 1999(Wang et al, , 2014.…”