Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo.
Zic family zinc-finger proteins play various roles in animal development. In mice, five Zic genes (Zic1-5) have been reported. Despite the partly overlapping expression profiles of these genes, mouse mutants for each Zic show distinct phenotypes. To uncover possible redundant roles, we characterized Zic2/Zic3 compound mutant mice. Zic2 and Zic3 are both expressed in presomitic mesoderm, forming and newly generated somites with differential spatiotemporal accentuation. Mice heterozygous for the hypomorphic Zic2 allele together with null Zic3 allele generally showed severe malformations of the axial skeleton, including asymmetric or rostro-caudally bridged vertebrae, and reduction of the number of caudal vertebral bones, that are not obvious in single mutants. These defects were preceded by perturbed somitic marker expression, and reduced paraxial mesoderm progenitors in the primitive streak. These results suggest that Zic2 and Zic3 cooperatively control the segmentation of paraxial mesoderm at multiple stages. In addition to the segmentation abnormality, the compound mutant also showed neural tube defects that ran the entire rostro-caudal extent (craniorachischisis), suggesting that neurulation is another developmental process where Zic2 and Zic3 have redundant functions.
Inoue
Takashi
T
Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.
Ota
Maya
M
Mikoshiba
Katsuhiko
K
Aruga
Jun
J
D000818:Animals; D001846:Bone Development / Q000235:genetics; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000378:metabolism*; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D009432:Neural Crest / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D005819:Genetic Markers; D018398:Homeodomain Proteins; D014157:Transcription Factors; C491811:Zic2 protein, mouse; C491594:Zic3 protein, mouse