title: Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives.
abstract: Zic family genes encode zinc finger proteins, which are homologues of the Drosophila pair-rule gene odd-paired. In the present study, we characterized the fifth member of the mouse Zic family gene, mouse Zic5. Zic5 is located near Zic2, which is responsible for human brain malformation syndrome (holoprosencephaly, or HPE). In embryonic stages, Zic5 was expressed in dorsal part of neural tissues and limbs. Expression of Zic5 overlapped with those of other Zic genes, most closely with Zic2, but was not identical. Targeted disruption of Zic5 resulted in insufficient neural tube closure at the rostral end, similar to that seen in Zic2 mutant mice. In addition, the Zic5-deficient mice exhibited malformation of neural-crest-derived facial bones, especially the mandible, which had not been observed in other Zic family mutants. During the embryonic stages, there were delays in the development of the first branchial arch and extension of the trigeminal and facial nerves. Neural crest marker staining revealed fewer neural crest cells in the dorsal cephalic region of the mutant embryos without significant changes in their migration. When mouse Zic5 was overexpressed in Xenopus embryos, expression of a neural crest marker was enhanced. These findings suggested that Zic5 is involved in the generation of neural crest tissue in mouse development. ZIC5 is also located close to ZIC2 in humans, and deletions of 13q32, where ZIC2 is located, lead to congenital brain and digit malformations known as the "13q32 deletion syndrome". Based on both their similar expression pattern in mouse embryos and the malformations observed in Zic5-deficient mutant mice, human ZIC5 might be involved in the deletion syndrome.
authors.affiliation: Laboratory for Developmental Neurobiology and Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute,Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inoue
authors.forename: Minoru
authors.initials: M
authors.lastname: Hatayama
authors.forename: Takahide
authors.initials: T
authors.lastname: Tohmonda
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Jun
authors.initials: J
authors.lastname: Aruga
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000818:Animals; D019521:Body Patterning; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D019465:Craniofacial Abnormalities / Q000235:genetics; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009420:Nervous System / Q000033:anatomy & histology / Q000196:embryology*; D009432:Neural Crest / Q000002:abnormalities / Q000166:cytology / Q000502:physiology*; D009436:Neural Tube Defects / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C418623:Zic5 protein, mouse