Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



ID: 229464.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
The mouse homeobox gene Not is required for caudal notochord development and affected by the truncate mutation
Authors:Abdelkhalek, Hanaa Ben; Beckers, Anja; Schuster-Gossler, Karin; Pavlova, Maria N.; Burkhardt, Hannelore; Lickert, Heiko; Rossant, Janet; Reinhardt, Richard; Schalkwyk, Leonard C.; Müller, Ines; Herrmann, Bernhard G.; Ceolin, Marcelo; Rivera-Pomar, Rolando; Gossler, Achim
Language:English
Date of Publication (YYYY-MM-DD):2004-07-15
Title of Journal:Genes and Development
Journal Abbrev.:Genes Dev
Volume:18
Issue / Number:14
Start Page:1725
End Page:1736
Copyright:© 2004 by Cold Spring Harbor Laboratory Press
Review Status:not specified
Audience:Experts Only
Abstract / Description:The floating head (flh) gene in zebrafish encodes a homeodomain protein, which is essential for notochord formation along the entire body axis. flh orthologs, termed Not genes, have been isolated from chick and Xenopus, but no mammalian ortholog has yet been identified. Truncate (tc) is an autosomal recessive mutation in mouse that specifically disrupts the development of the caudal notochord. Here, we demonstrate that truncate arose by a mutation in the mouse Not gene. The truncate allele (Nottc) contains a point mutation in the homeobox of Not that changes a conserved Phenylalanine residue in helix 1 to a Cysteine (F20C), and significantly destabilizes the homeodomain. Reversion of F20C in one allele of homozygous tc embryonic stem (ES) cells is sufficient to restore normal notochord formation in completely ES cell-derived embryos. We have generated a targeted mutation of Not by replacing most of the Not coding sequence, including the homeobox with the eGFP gene. The phenotype of NoteGFP/eGFP, NoteGFP/tc, and Nottc/tc embryos is very similar but slightly more severe in NoteGFP/eGFP than in Nottc/tc embryos. This confirms allelism of truncate and Not, and indicates that tc is not a complete null allele. Not expression is abolished in Foxa2 and T mutant embryos, suggesting that Not acts downstream of both genes during notochord development. This is in contrast to zebrafish embryos, in which flh interacts with ntl (zebrafish T) in a regulatory loop and is essential for development of the entire notochord, and suggests that different genetic control circuits act in different vertebrate species during notochord formation.
Free Keywords:Notochord development; Not gene; homeodomain protein
Comment of the Author/Creator:Published online: 2004-07-01
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Institute for Molecular Biology OE5250, Medizinische Hochschule Hannover, D-30625 Hannover, Germany;
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Ontario, Canada;
Max-Planck-Institute for Biophysical Chemistry, D-37077 Göttingen, Germany
Relations:Has References-ISSN:0890-9369
Has References-DOI:10.1101/gad.303504
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.