Fibulin-1 is required for morphogenesis of neural crest-derived structures.
Here we report that mouse embryos homozygous for a gene trap insertion in the fibulin-1 (Fbln1) gene are deficient in Fbln1 and exhibit cardiac ventricular wall thinning and ventricular septal defects with double outlet right ventricle or overriding aorta. Fbln1 nulls also display anomalies of aortic arch arteries, hypoplasia of the thymus and thyroid, underdeveloped skull bones, malformations of cranial nerves and hemorrhagic blood vessels in the head and neck. The spectrum of malformations is consistent with Fbln1 influencing neural crest cell (NCC)-dependent development of these tissues. This is supported by evidence that Fbln1 expression is associated with streams of cranial NCCs migrating adjacent to rhombomeres 2-7 and that Fbln1-deficient embryos display patterning anomalies of NCCs forming cranial nerves IX and X, which derive from rhombomeres 6 and 7. Additionally, Fbln1-deficient embryos show increased apoptosis in areas populated by NCCs derived from rhombomeres 4, 6 and 7. Based on these findings, it is concluded that Fbln1 is required for the directed migration and survival of cranial NCCs contributing to the development of pharyngeal glands, craniofacial skeleton, cranial nerves, aortic arch arteries, cardiac outflow tract and cephalic blood vessels.
Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Marion A
MA
Cooley
Christine B
CB
Kern
Victor M
VM
Fresco
Andy
A
Wessels
Robert P
RP
Thompson
Tim C
TC
McQuinn
Waleed O
WO
Twal
Corey H
CH
Mjaatvedt
Christopher J
CJ
Drake
W Scott
WS
Argraves
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000235:genetics; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004721:Endoplasmic Reticulum / Q000502:physiology; D005318:Fetal Heart / Q000473:pathology / Q000502:physiology; D005838:Genotype; D006352:Heart Ventricles / Q000196:embryology / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology*; D009432:Neural Crest / Q000502:physiology*; D016133:Polymerase Chain Reaction; D001616:beta-Galactosidase / Q000235:genetics
D015704:CD4 Antigens; D002135:Calcium-Binding Proteins; C060820:fibulin; D001616:beta-Galactosidase