International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

Dr Zoha Kibar
McGill University
3655 Sir William Osler Promenade
Room 910
Montreal, PQ
H3G1Y6
Canada

Co-Authors: 1)Vogan K, 2)Groulx N, 3)Justice M, 4)Underhill A, 2)Gros P
Institutions: 1)Dept of Genetics, Harvard Medical School 2)Dept of Biochemistry, McGill University, 3)Dept of Molecular and Human Genetics, Baylor College of Medicine, 4)Dept of Medical Genetics, University of Alberta, and Dept of Biochemistry, McGill University

Mice homozygous for the Loop-tail (Lp) mutation exhibit a profound defect in neurulation that results in an open neural tube in the hindbrain and spinal region, a condition similar to craniorachischisis in humans. A positional cloning approach has led to the isolation and characterization of a novel Lp candidate gene, Ltap. Ltap is expressed embryonically in a tissue-specific fashion in structures affected by Lp, from the earlier stages of neural induction in the neural ectoderm, to the late stages of neural tube closure in the neuroepithelium. Significantly, alterations in Ltap were identified in two independent alleles of the Loop-tail mutation (Lp, Lpm1Jus). These alterations are specific to the Lp chromosomes, and are absent from the parental strains and from a large number of inbred strains tested. Ltap encodes a putative membrane protein with a PDZ domain-binding motif, and that shares striking similarity to the Drosophila protein Strabismus/Van Gogh, a member of the wingless/frizzled/dishevelled pathway required for proper tissue polarity and cell fate specification in the fly. These findings suggest that mutations in Ltap are responsible for the Lp phenotype and identify a key role for this novel gene in neurogenesis. In addition, the presented data support an evolutionarily conserved role for members of this gene family in regulating tissue polarity decisions during animal morphogenesis.