Dll4, a Novel Notch Ligand Expressed in Arterial Endothelium

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2000 Jun 3

PMID 10837024

Citations 179

Authors

J R Shutter

S Scully

W Fan

W G Richards

J Kitajewski

G A Deblandre

C R Kintner

K L Stark

Affiliations

Soon will be listed here.

Abstract

We report the cloning and characterization of a new member of the Delta family of Notch ligands, which we have named Dll4. Like other Delta genes, Dll4 is predicted to encode a membrane-bound ligand, characterized by an extracellular region containing several EGF-like domains and a DSL domain required for receptor binding. In situ analysis reveals a highly selective expression pattern of Dll4 within the vascular endothelium. The activity and expression of Dll4 and the known actions of other members of this family suggest a role for Dll4 in the control of endothelial cell biology.

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References

Muskavitch M . Delta-notch signaling and Drosophila cell fate choice. Dev Biol. 1994; 166(2):415-30. DOI: 10.1006/dbio.1994.1326. View

Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssiere C . Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet. 1997; 350(9090):1511-5. DOI: 10.1016/S0140-6736(97)08083-5. View

Chitnis A, Henrique D, Lewis J, Ish-Horowicz D, Kintner C . Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta. Nature. 1995; 375(6534):761-6. DOI: 10.1038/375761a0. View

Knecht A, Good P, Dawid I, Harland R . Dorsal-ventral patterning and differentiation of noggin-induced neural tissue in the absence of mesoderm. Development. 1995; 121(6):1927-35. DOI: 10.1242/dev.121.6.1927. View

Bettenhausen B, Hrabe de Angelis M, Simon D, Guenet J, Gossler A . Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta. Development. 1995; 121(8):2407-18. DOI: 10.1242/dev.121.8.2407. View

Nye J, Kopan R . Developmental signaling. Vertebrate ligands for Notch. Curr Biol. 1995; 5(9):966-9. DOI: 10.1016/s0960-9822(95)00189-8. View

Zhong T, Rosenberg M, Mohideen M, WEINSTEIN B, Fishman M . gridlock, an HLH gene required for assembly of the aorta in zebrafish. Science. 2000; 287(5459):1820-4. DOI: 10.1126/science.287.5459.1820. View

Jiang R, Lan Y, Chapman H, Shawber C, Norton C, Serreze D . Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice. Genes Dev. 1998; 12(7):1046-57. PMC: 316673. DOI: 10.1101/gad.12.7.1046. View

Wang H, Chen Z, Anderson D . Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell. 1998; 93(5):741-53. DOI: 10.1016/s0092-8674(00)81436-1. View

10.

Kusumi K, Sun E, Kerrebrock A, Bronson R, Chi D, Bulotsky M . The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries. Nat Genet. 1998; 19(3):274-8. DOI: 10.1038/961. View

11.

Fleming R . Structural conservation of Notch receptors and ligands. Semin Cell Dev Biol. 1999; 9(6):599-607. DOI: 10.1006/scdb.1998.0260. View

12.

Artavanis-Tsakonas S, Rand M, Lake R . Notch signaling: cell fate control and signal integration in development. Science. 1999; 284(5415):770-6. DOI: 10.1126/science.284.5415.770. View

13.

Deblandre G, Wettstein D, Kintner C . A two-step mechanism generates the spacing pattern of the ciliated cells in the skin of Xenopus embryos. Development. 1999; 126(21):4715-28. DOI: 10.1242/dev.126.21.4715. View

14.

Gallahan D, Callahan R . Mammary tumorigenesis in feral mice: identification of a new int locus in mouse mammary tumor virus (Czech II)-induced mammary tumors. J Virol. 1987; 61(1):66-74. PMC: 255203. DOI: 10.1128/JVI.61.1.66-74.1987. View

15.

Kintner C, Melton D . Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction. Development. 1987; 99(3):311-25. DOI: 10.1242/dev.99.3.311. View

16.

Ellisen L, Bird J, West D, Soreng A, Reynolds T, Smith S . TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991; 66(4):649-61. DOI: 10.1016/0092-8674(91)90111-b. View

17.

Oschwald R, Richter K, Grunz H . Localization of a nervous system-specific class II beta-tubulin gene in Xenopus laevis embryos by whole-mount in situ hybridization. Int J Dev Biol. 1991; 35(4):399-405. View

18.

Harland R . In situ hybridization: an improved whole-mount method for Xenopus embryos. Methods Cell Biol. 1991; 36:685-95. DOI: 10.1016/s0091-679x(08)60307-6. View

19.

Kintner C, Dodd J . Hensen's node induces neural tissue in Xenopus ectoderm. Implications for the action of the organizer in neural induction. Development. 1991; 113(4):1495-505. DOI: 10.1242/dev.113.4.1495. View

20.

del Amo F, Swiatek P, Jenkins N, Copeland N, Gridley T . Cloning, analysis, and chromosomal localization of Notch-1, a mouse homolog of Drosophila Notch. Genomics. 1993; 15(2):259-64. DOI: 10.1006/geno.1993.1055. View