A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice

Smita M. Purandare, Stephanie Ware, Kin Ming Kwan, Marinella Gebbia, Maria Teresa Bassi, Jian Min Deng, Hannes Vogel, Richard R. Behringer, John W. Belmont, Brett Casey

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

X-linked heterotaxy (HTX1) is a rare developmental disorder characterized by disturbances in embryonic laterality and other midline developmental field defects. HTX1 results from mutations in ZIC3, a member of the GLI transcription factor superfamily. A targeted deletion of the murine Zic3 locus has been created to investigate its function and interactions with other molecular components of the left-right axis pathway. Embryonic lethality is seen in approximately 50% of null mice with an additional 30% lethality in the perinatal period. Null embryos have defects in turning, cardiac development and neural tube closure. Malformations in live born null mice include complex congenital heart defects, pulmonary reversal or isomerism, CNS defects and vertebral/rib anomalies. Investigation of nodal expression in Zic3-deficient mice indicates that, although nodal is initially expressed symmetrically in the node, there is failure to maintain expression and to shift to asymmetric expression. Subsequent nodal and Pitx2 expression in the lateral plate mesoderm in these mice is randomized, indicating that Zic3 acts upstream of these genes in the determination of left-right asymmetry. The phenotype of these mice correctly models the defects found in human HTX1 and indicates an important role for Zic3 in both left-right and axial patterning.

Original languageEnglish (US)
Pages (from-to)2293-2302
Number of pages10
JournalDevelopment (Cambridge)
Volume129
Issue number9
StatePublished - 2002
Externally publishedYes

Fingerprint

Skeleton
Central Nervous System
Isomerism
Neural Tube
Congenital Heart Defects
Ribs
Mesoderm
Transcription Factors
Embryonic Structures
Phenotype
Lung
Mutation
Genes

Keywords

  • CNS
  • Left-right asymmetry
  • Mouse
  • Zic3

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Purandare, S. M., Ware, S., Kwan, K. M., Gebbia, M., Bassi, M. T., Deng, J. M., ... Casey, B. (2002). A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice. Development (Cambridge), 129(9), 2293-2302.

A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice. / Purandare, Smita M.; Ware, Stephanie; Kwan, Kin Ming; Gebbia, Marinella; Bassi, Maria Teresa; Deng, Jian Min; Vogel, Hannes; Behringer, Richard R.; Belmont, John W.; Casey, Brett.

In: Development (Cambridge), Vol. 129, No. 9, 2002, p. 2293-2302.

Research output: Contribution to journalArticle

Purandare, SM, Ware, S, Kwan, KM, Gebbia, M, Bassi, MT, Deng, JM, Vogel, H, Behringer, RR, Belmont, JW & Casey, B 2002, 'A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice', Development (Cambridge), vol. 129, no. 9, pp. 2293-2302.
Purandare, Smita M. ; Ware, Stephanie ; Kwan, Kin Ming ; Gebbia, Marinella ; Bassi, Maria Teresa ; Deng, Jian Min ; Vogel, Hannes ; Behringer, Richard R. ; Belmont, John W. ; Casey, Brett. / A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice. In: Development (Cambridge). 2002 ; Vol. 129, No. 9. pp. 2293-2302.
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