Transcriptional oscillation of Lunatic fringe is essential for somitogenesis

Abstract

A molecular oscillator that controls the expression of cyclic genes such as lunatic fringe (Lfng) in the presomitic mesoderm has been shown to be coupled with somite formation in vertebrate embryos. To address the functional significance of oscillatingLfngexpression, we have generated transgenic mice expressingLfngconstitutively in the presomitic mesoderm in addition to the intrinsic cyclicLfngactivity. These transgenic lines displayed defects of somite patterning and vertebral organization that were very similar to those ofLfngnull mutants. Furthermore, constitutive expression of exogenousLfngdid not compensate for the complete loss of cyclic endogenousLfngactivity. Noncyclic exogenousLfngexpression did not abolish cyclic expression of endogenousLfngin the posterior presomitic mesoderm (psm) but affected its expression pattern in the anterior psm. Similarly, dynamic expression ofHes7was not abolished but abnormal expression patterns were obtained. Our data are consistent with a model in which alternations ofLfngactivity between ON and OFF states in the presomitic mesoderm prior to somite segmentation are critical for proper somite patterning, and suggest that Notch signaling might not be the only determinant of cyclic gene expression in the presomitic mesoderm of mouse embryos.