Spatiotemporal expression of long noncoding RNA Moshe modulates heart cell lineage commitment

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• Long non-coding RNAs (LncRNAs) play crucial roles in biological development.
• Congenital heart defects (CHDs), including atrial septal defect (ASD), are linked to developmental abnormalities.
• Gata6 is a key gene in heart development and is associated with ASD.

Purpose of the Study:

• To characterize the molecular function of the lncRNA Moshe (1010001N08ik-203), an antisense transcript of Gata6.
• To investigate Moshe's role in cardiac development and its potential involvement in ASD.
• To elucidate the regulatory mechanism of Moshe on gene expression during cardiogenesis.

Main Methods:

• Analysis of Moshe expression during mouse embryonic development (E8.5-E12.5).
• Knockdown of Moshe during cardiogenesis to assess its functional impact on gene expression.
• Chromatin Isolation by RNA Purification (ChIRP) to determine Moshe's direct binding to target gene promoters.

Main Results:

• Moshe expression is detected during cardiac mesoderm and atrioventricular septum development.
• Moshe knockdown represses Nkx2.5 expression and increases expression of major second heart field (SHF) lineage genes.
• Moshe directly binds to the Nkx2.5 promoter region, activating its gene expression.

Conclusions:

• Moshe is a heart-enriched lncRNA essential for regulating cardiogenesis.
• Moshe controls a network of cardiac development genes, including Nkx2.5, and influences SHF lineage gene expression.
• Moshe may play a significant role in the pathogenesis of atrial septal defects.