Zic2 Regulates the Kinetics of Neurulation

Mutation in human ZIC2, a zinc finger protein homologous to Drosophila odd-paired, causes holoprosencephaly (HPE), which is a common, severe malformation of the brain in humans. However, the pathogenesis is largely unknown. Here we show that reduced expression (knockdown) of mouse Zic2 causes neurul...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-02, Vol.97 (4), p.1618-1623
Main Authors: Nagai, Takeharu, Aruga, Jun, Minowa, Osamu, Sugimoto, Takashi, Ohno, Yoshiki, Noda, Tetsuo, Mikoshiba, Katsuhiko
Format: Article
Language:English
Subjects:
Alleles
Animals
Biological Sciences
Biology
Bone and Bones - embryology
Bone and Bones - pathology
Cell Differentiation
Central Nervous System - embryology
Central Nervous System - pathology
Disease Models, Animal
Embryonic and Fetal Development
Embryos
Gene Expression Regulation, Developmental
Gene Targeting
Genetic mutation
holoprosencephaly
Holoprosencephaly - embryology
Humans
In Situ Hybridization
In Situ Nick-End Labeling
Mice
Mice, Knockout
Mutation
Neural crest
Neural tube defects
Neural Tube Defects - genetics
Neurology
Neurons
Nuclear Proteins
Prenatal development
Proteins
Proteins - genetics
Reverse transcriptase polymerase chain reaction
Spina bifida
Spinal cord
Spinal Dysraphism - embryology
Transcription Factors - genetics
Transcription Factors - pharmacology
Wnt Proteins
Wnt-3a gene
Wnt3 Protein
Wnt3A Protein
Zic2 gene
Zic2 protein
Zinc
Zinc Fingers
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Summary:Mutation in human ZIC2, a zinc finger protein homologous to Drosophila odd-paired, causes holoprosencephaly (HPE), which is a common, severe malformation of the brain in humans. However, the pathogenesis is largely unknown. Here we show that reduced expression (knockdown) of mouse Zic2 causes neurulation delay, resulting in HPE and spinal bifida. Differentiation of the most dorsal neural plate, which gives rise to both roof plate and neural crest cells, also was delayed as indicated by the expression lag of a roof plate marker, Wnt3a. In addition the development of neural crest derivatives such as dorsal root ganglion was impaired. These results suggest that the Zic2 expression level is crucial for the timing of neurulation. Because the Zic2 knockdown mouse is the first mutant with HPE and spina bifida to survive to the perinatal period, the mouse will promote analyses of not only the neurulation but also the pathogenesis of human HPE.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.97.4.1618