Oscillatory lunatic fringe activity is crucial for segmentation of the anterior but not posterior skeleton.
The Notch pathway plays multiple roles during vertebrate somitogenesis, functioning in the segmentation clock and during rostral/caudal (R/C) somite patterning. Lunatic fringe (Lfng) encodes a glycosyltransferase that modulates Notch signaling, and its expression patterns suggest roles in both of these processes. To dissect the roles played by Lfng during somitogenesis, a novel allele was established that lacks cyclic Lfng expression within the segmentation clock, but that maintains expression during R/C somite patterning (Lfng(DeltaFCE1)). In the absence of oscillatory Lfng expression, Notch activation is ubiquitous in the PSM of Lfng(DeltaFCE1) embryos. Lfng(DeltaFCE1) mice exhibit severe segmentation phenotypes in the thoracic and lumbar skeleton. However, the sacral and tail vertebrae are only minimally affected in Lfng(DeltaFCE1) mice, suggesting that oscillatory Lfng expression and cyclic Notch activation are important in the segmentation of the thoracic and lumbar axial skeleton (primary body formation), but are largely dispensable for the development of sacral and tail vertebrae (secondary body formation). Furthermore, we find that the loss of cyclic Lfng has distinct effects on the expression of other clock genes during these two stages of development. Finally, we find that Lfng(DeltaFCE1) embryos undergo relatively normal R/C somite patterning, confirming that Lfng roles in the segmentation clock are distinct from its functions in somite patterning. These results suggest that the segmentation clock may employ varied regulatory mechanisms during distinct stages of anterior/posterior axis development, and uncover previously unappreciated connections between the segmentation clock, and the processes of primary and secondary body formation.
Shifley
Emily T
ET
Department of Molecular Genetics, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210-1292, USA.
Vanhorn
Kellie M
KM
Perez-Balaguer
Ariadna
A
Franklin
John D
JD
Weinstein
Michael
M
Cole
Susan E
SE
D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000502:physiology*; D001846:Bone Development; D001842:Bone and Bones / Q000002:abnormalities / Q000196:embryology*; D004247:DNA / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D016695:Glycosyltransferases / Q000172:deficiency / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D009991:Oscillometry; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology; D017384:Sequence Deletion; D013131:Spine / Q000002:abnormalities; D015017:Yolk Sac / Q000502:physiology
D051880:Receptors, Notch; D004247:DNA; D016695:Glycosyltransferases; C498392:Lfng protein, mouse