title: Neural crest defects in ephrin-B2 mutant mice are non-autonomous and originate from defects in the vasculature.
abstract: Ephrin-B2, a member of the Eph/ephrin family of cell signaling molecules, has been implicated in the guidance of cranial and trunk neural crest cells (NCC) and development of the branchial arches(BA), but detailed examination in mice has been hindered by embryonic lethality of Efnb2 null loss of function due to a requirement in angiogenic remodeling. To elucidate the developmental roles for Efnb2, we generated a conditional rescue knock-in allele that allows rescue of ephrin-B2 specifically in the vascular endothelium (VE), but is otherwise ephrin-B2 deficient. Restoration of ephrin-B2 expression specifically to the VE completely circumvents angiogenic phenotypes, indicating that the requirement of ephrin-B2 in angiogenesis is limited to the VE. Surprisingly, we find that expression of ephrin-B2 specifically in the VE is also sufficient for normal NCC migration and that conversely, embryos in which ephrin-B2 is absent specifically from the VE exhibit NCC migration and survival defects. Disruption of vascular development independent of loss of ephrin-B2 function also leads to defects in NCC and BA development. Together, these data indicate that direct ephrin-B2 signaling to NCCs is not required for NCC guidance, which instead depends on proper organization of the embryonic vasculature.
authors.affiliation: Department of Cell and Tissue Biology, Program in Craniofacial Biology and Institute for Human Genetics, University of California, San Francisco, CA 94143, United States.
authors.forename: Ace E
authors.initials: AE
authors.lastname: Lewis
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hwa
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Developmental and Regenerative Biology, Mt. Sinai School of Medicine, New York, NY 10029, United States.
authors.forename: Philippe
authors.initials: P
authors.lastname: Soriano
authors.affiliation: Department of Cell and Tissue Biology, Program in Craniofacial Biology and Institute for Human Genetics, University of California, San Francisco, CA 94143, United States. Electronic address: Jeffrey.bush@ucsf.edu.
authors.forename: Jeffrey O
authors.initials: JO
authors.lastname: Bush
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D002465:Cell Movement / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism*; D036388:Ephrin-B2 / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006652:Histological Techniques; D017403:In Situ Hybridization; D051379:Mice; D009154:Mutation / Q000235:genetics; D009432:Neural Crest / Q000002:abnormalities* / Q000502:physiology*; D010641:Phenotype
chemical_list: D017931:DNA Primers; D036388:Ephrin-B2
keywords: Angiogenesis; Bidirectional signaling; Branchial arches; Craniofacial; Eph; Ephrin; Foregut; Hindgut; Neural crest; Palate; Pharyngeal arches; Reverse signaling