"An international team of scientists from the UK, the USA and Japan have revealed new aspects of how developing embryos establish a left and a right hand side.
While we are externally mirror symmetrical between left and right, our internal organs are asymmetrically positioned and patterned (the heart lies towards the left and the liver towards the right side of the body). This asymmetry is established between 19 and 22 days of development in humans, before the mother even knows that she is pregnant. If this process goes wrong, it can lead to birth defects and is particularly associated with congenital heart disease. New research, published in the journal PLoS Genetics provides insight into how this process happens and the ways in which it can go wrong.
The earliest known event in mammalian left-right (L-R) patterning, surprisingly, is not an asymmetry in where a gene functions, but a physical flow of fluid (from right to left) within a short-lived pit in the embryo. This tear shaped pit is known as the node. The direction of this 'nodal flow' determines which side of the embryo will develop as the left. This leftward 'nodal flow' is driven by the action of motile cilia, hair-like structures protruding from the cell surface within the node.
Exactly how nodal flow is detected by the embryo remains unclear: we know that the cells directly surrounding the node (the crown cells) are required to detect nodal flow; that the crown cells must each have an immotile cilium and that they must contain the putative calcium channel protein Polycystin-2 (PKD2). Previously the research team implicated a second Polycystin protein, PKD1L1, in this pathway.
Describing these new findings, Dominic Norris, Programme Leader at the Medical Research Council (MRC) Harwell, explains, "Firstly, we have been able to define a genetic pathway in which each element represses the next..."
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