MLC3F transgene expression in iv mutant mice reveals the importance of left-right signalling pathways for the acquisition of left and right atrial but not ventricular compartment identity

Transcriptional differences between left and right cardiac chambers are rev ealed by an nlacZ reporter transgene controlled by regulatory sequences of the MLC3F gene, which is expressed in the left ventricle (LV), atrioventric ular canal (AVC), and right atrium (RA), To examine the role of left-right signalling in the acquisition of left and right chamber identity, we have i nvestigated MLC3F transgene expression in iv mutant mice. iv/iv mice exhibi t randomised direction of heart looping and an elevated frequency of associ ated laterality defects, including atrial isomerism, At fetal stages, 3F-nl acZ-2E transgene expression remains confined to the morphological LV, AVC, and RA in L-loop hearts, although these appear on the opposite side of the body. In cases of morphologically distinguishable right atrial appendage is omerism, both atrial appendages show strong transgene expression. Conversel y, specimens with morphological left atrial appendage isomerism show only w eak expression in both atrial appendages. The earliest left-right atrial di fferences in the expression of the 3F-nLacZ-2E transgene are observed at E8 .5. DiI labelling experiments confirmed that transcriptional regionalisatio n of the 3F-nlacZ-2E transgene at this stage reflects future atrial chamber identity, In some iv/iv embryos at E8.5, the asymmetry of 3F-nlacZ-2E expr ession was lost, suggesting atrial isomerism at the transcriptional level p rior to chamber formation. These data suggest that molecular specification of left and right atrial but not ventricular chambers is dependent on left- right axial cues. (C) 2001 Wiley-Liss, Inc.