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Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail

Nature Genetics volume 28, pages 251–255 (2001)Cite this article

Abstract

Neural tube defects (NTDs) such as spina bifida and anencephaly are common congenital malformations in humans (1/1,000 births) that result from failure of the neural tube to close during embryogenesis1,2. The etiology of NTDs is complex, with both genetic and environmental contributions; the genetic component has been extensively studied with mouse models3. Loop-tail (Lp) is a semidominant mutation on mouse chromosome 1 (ref. 4). In the two known Lp alleles (Lp, Lpm1Jus), heterozygous mice exhibit a characteristic looped tail, and homozygous embryos show a completely open neural tube in the hindbrain and spinal region, a condition similar to the severe craniorachischisis defect in humans4,5,6. Morphological and neural patterning studies indicate a role for the Lp gene product in controlling early morphogenesis and patterning of both axial midline structures and the developing neural plate7. The 0.6-cM/0.7-megabase (Mb) Lp interval is delineated proximally by D1Mit113/Apoa2/Fcer1g and distally by Fcer1a/D1Mit149/Spna1 and contains a minimum of 17 transcription units8,9,10,11. One of these genes, Ltap, encodes a homolog of Drosophila Strabismus/Van Gogh (Stbm/Vang), a component of the frizzled/dishevelled tissue polarity pathway12,13,14. Ltap is expressed broadly in the neuroectoderm throughout early neurogenesis and is altered in two independent Lp alleles, identifying this gene as a strong candidate for Lp.

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Figure 1: Organization of the Lp candidate region.
Figure 2: Characterization of the ORF for Ltap.
Figure 3: Ltap mRNA expression in embryonic and adult tissues and in Lp.
Figure 4: Expression of Ltap from E7.0 to E8.5.
Figure 5: Expression of Ltap from E8.5 to E10.0.

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GenBank/EMBL/DDBJ

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Acknowledgements

We thank M. Mathieu for expert technical assistance in DNA sequencing, D. Malo for supplying DNA from inbred strains and R. Krumlauf for providing the Krox20 probe. We especially thank C. Tabin for supporting aspects of this study in his laboratory and for providing helpful advice during the course of this work. The BAC clone was provided by the MRC Genome Resource Facility. This study was supported by grants from the Canadian Institute for Health Research (CIHR) of Canada (to P.G.) and NIH Public Health Service grant P01 CA75719 (to M.J). Z.K. is supported by a fellowship from the Fonds de la Recherche en Santé du Québec. K.J.V. is a Genetics Institute Fellow of the Life Sciences Research Foundation. D.A.U. is a Scholar of the Alberta Heritage Foundation for Medical Research. P.G. is supported by a Distinguished Scientist Award of the CIHR and is an International Scholar for the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Biochemistry, McGill University, Montreal, Canada

    Zoha Kibar, Normand Groulx & Philippe Gros

  2. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA

    Kyle J. Vogan

  3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA

    Monica J. Justice

  4. Department of Medical Genetics, University of Alberta, Edmonton, Canada

    D. Alan Underhill

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  1. Zoha Kibar
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Correspondence to Philippe Gros.

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Kibar, Z., Vogan, K., Groulx, N. et al. Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail. Nat Genet 28, 251–255 (2001). https://doi.org/10.1038/90081

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