The SIL gene is required for mouse embryonic axial development and left-right specification

The establishment of the main body axis and the determination of left-right asymmetry are fundamental aspects of vertebrate embryonic development. A l ink between these processes has been revealed by the frequent finding of mi dline defects in humans with left-right anomalies(1). This association is a lso seen in a number of mutations in mouse(2-4) and zebrafish(1,5), and in experimentally manipulated Xenopus embryos(5). However, the severity of lat erality defects accompanying abnormal midline development varies(6), and th e molecular basis for this variation is unknown. Here we show that mouse em bryos lacking the early-response gene SIL have axial midline defects, a blo ck in midline Sonic hedgehog (Shh) signalling and randomized cardiac loopin g. Comparison with Shh mutant embryos(7), which have axial defects but norm al cardiac looping, indicates that the consequences of abnormal midline dev elopment for left-right patterning depend on the time of onset, duration an d severity of disruption of the normal asymmetric patterns of expression of nodal, lefty-2 and Pitx2.