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 link between these processes has been revealed by the frequent finding of midline defects in humans with left-right anomalies. This association is also seen in a number of mutations in mouse and zebrafish, and in experimentally manipulated Xenopus embryos. However, the severity of laterality defects accompanying abnormal midline development varies, and the molecular basis for this variation is unknown. Here we show that mouse embryos lacking the early-response gene SIL have axial midline defects, a block in midline Sonic hedgehog (Shh) signalling and randomized cardiac looping. Comparison with Shh mutant embryos, which have axial defects but normal cardiac looping, indicates that the consequences of abnormal midline development for left-right patterning depend on the time of onset, duration and severity of disruption of the normal asymmetric patterns of expression of nodal, lefty-2 and Pitx2.
Izraeli
S
S
Genetics Department, Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20889-5105, USA.
Lowe
L A
LA
Bertness
V L
VL
Good
D J
DJ
Dorward
D W
DW
Kirsch
I R
IR
Kuehn
M R
MR
D000818:Animals; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D004622:Embryo, Mammalian / Q000002:abnormalities; D005314:Embryonic and Fetal Development / Q000235:genetics* / Q000502:physiology; D018390:Gene Targeting; D006321:Heart / Q000196:embryology; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D051379:Mice; D008819:Mice, Nude; D016296:Mutagenesis; D009436:Neural Tube Defects / Q000235:genetics; D055457:Nodal Protein; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D051761:Paired Box Transcription Factors; D011506:Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D000097577:Homeobox Protein PITX2
D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D055457:Nodal Protein; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D051761:Paired Box Transcription Factors; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000097577:Homeobox Protein PITX2; C526161:LEFTY1 protein, human; C526007:NODAL protein, human; C526008:Nodal protein, mouse; C509239:SHH protein, human; C071236:STIL protein, human; C101485:homeobox protein PITX1; C433629:homeobox protein PITX3