Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice
Rulang Jiang,Yu Lan,H D Chapman,Carrie J. Shawber,Christine R. Norton,David V. Serreze,Gerry Weinmaster,Thomas Gridley +7 more
TLDR
It is demonstrated that Notch signaling mediated by Jag2 plays an essential role during limb, craniofacial, and thymic development in mice, as well as in the foot plates of the mutant homozygotes.Abstract:
The Notch signaling pathway is a conserved intercellular signaling mechanism that is essential for proper embryonic development in numerous metazoan organisms. We have examined the in vivo role of the Jagged2 (Jag2) gene, which encodes a ligand for the Notch family of transmembrane receptors, by making a targeted mutation that removes a domain of the Jagged2 protein required for receptor interaction. Mice homozygous for this deletion die perinatally because of defects in craniofacial morphogenesis. The mutant homozygotes exhibit cleft palate and fusion of the tongue with the palatal shelves. The mutant mice also exhibit syndactyly (digit fusions) of the fore- and hindlimbs. The apical ectodermal ridge (AER) of the limb buds of the mutant homozygotes is hyperplastic, and we observe an expanded domain of Fgf8 expression in the AER. In the foot plates of the mutant homozygotes, both Bmp2 and Bmp7 expression and apoptotic interdigital cell death are reduced. Mutant homozygotes also display defects in thymic development, exhibiting altered thymic morphology and impaired differentiation of γδ lineage T cells. These results demonstrate that Notch signaling mediated by Jag2 plays an essential role during limb, craniofacial, and thymic development in mice.read more
Citations
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HES and HERP families: multiple effectors of the Notch signaling pathway.
TL;DR: The identification of the HERP family as a Notch effector that cooperates with HES/E(spl) family has opened a new avenue to the authors' understanding of the Notch signaling pathway.
Journal ArticleDOI
Notch signaling is essential for vascular morphogenesis in mice.
Luke T. Krebs,Yingzi Xue,Christine R. Norton,John R. Shutter,Maureen Maguire,John P. Sundberg,Daniel Gallahan,Violaine Closson,Jan Kitajewski,Robert Callahan,Gilbert H. Smith,Kevin Lee Stark,Thomas Gridley +12 more
TL;DR: An essential role for the Notch signaling pathway in regulating embryonic vascular morphogenesis and remodeling is revealed and it is indicated that whereas the NotCh4 gene is not essential during embryonic development, the notch4 and Notch1 genes have partially overlapping roles during embryogenesis in mice.
Journal ArticleDOI
Notch signaling: simplicity in design, versatility in function
TL;DR: Recent studies in nematodes, Drosophila and vertebrate systems that begin to shed light on how versatility in Notch signaling output is generated, how signal strength is modulated, and how cross-talk between the Notch pathway and other intracellular signaling systems, such as the Wnt, hypoxia and BMP pathways, contributes to signaling diversity.
Journal ArticleDOI
Embryonic Lethality and Vascular Defects in Mice Lacking the Notch Ligand Jagged1
Yingzi Xue,Xiang Gao,Claire E. Lindsell,Christine R. Norton,Bo Chang,Carol Hicks,Maureen Gendron-Maguire,Elizabeth B. Rand,Gerry Weinmaster,Thomas Gridley +9 more
TL;DR: The phenotype of Cm /+ mice is established as a contiguous gene deletion syndrome and it is demonstrated that Jag1 is essential for remodeling of the embryonic vasculature.
Journal ArticleDOI
Radial Glial Identity Is Promoted by Notch1 Signaling in the Murine Forebrain
TL;DR: It is suggested that Notch1 promotes radial glial identity during embryogenesis, and that radial glia may be lineally related to stem cells in the adult nervous system.
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