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Learning how organs tell left from right

the heart.

Studies of the heart orientation in the Pitx2 knockout mice proved less conclusive. In the Pitx2 knockout mice, the heart was located on the right side of the body, not in its normal location on the left side. Despite its improper location, however, the direction of cardiac looping was normal.

"Everyone might well have predicted the result would be the same as after removal of Nodal," said Rosenfeld. "But now we know that this single transcription factor in the pathway does not account for the whole of left/right asymmetry."

Rosenfeld is now searching for other transcription factors that respond to Nodal signals. These transcription factors may be involved in a condition called situs invertus, which affects approximately 1 in 10,000 humans and gives rise to a mirror-image organization of the internal organs. In many cases the disorder has no adverse consequences, though it can be associated with heart abnormalities.

Rosenfeld also hopes to begin identifying genes that are switched on by Pitx2 when organs grow. Such genes are likely to provide additional insight into understanding left/right determination, he says.


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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
16-Sep-1999


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