Jagged 1 is necessary for normal mouse lens formation.
In mammals, two spatially and temporally distinct waves of fiber cell differentiation are crucial steps for normal lens development. In between these phases, an anterior growth zone forms in which progenitor cells migrate circumferentially, terminally exit the cell cycle and initiate differentiation at the lens equator. Much remains unknown about the molecular pathways orchestrating these processes. Previously, the Notch signal transduction pathway was shown to be critical for anterior lens progenitor cell growth and differentiation. However, the ligand or ligand(s) that direct these events are unknown. Using conditional gene targeting, we show that Jagged1 is required for lens fiber cell genesis, particularly that of secondary fiber cells. In the absence of Jagged1, the anterior growth and equatorial transition zones fail to develop fully, with only a handful of differentiated fiber cells present at birth. Adult Jagged1 conditional mutants completely lack lenses, along with severe anterior chamber deformities. Our data support the hypothesis that Jagged1-Notch signaling conveys a lateral inductive signal, which is indispensable for lens progenitor cell proliferation and differentiation.
Le
Tien T
TT
Division of Developmental Biology, Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Conley
Kevin W
KW
Brown
Nadean L
NL
D000818:Animals; D001035:Aphakia / Q000209:etiology / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000072100:Jagged-1 Protein; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology* / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008957:Models, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins