spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Theil, T.
Right arrow Articles by Wilkinson, D. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Theil, T.
Right arrow Articles by Wilkinson, D. G.
Development 129, 1477-1485 (2002)
© 2002 The Company of Biologists Limited

Requirement for downregulation of kreisler during late patterning of the hindbrain

Thomas Theil*, Linda Ariza-McNaughton{dagger}, Miguel Manzanares{ddagger}, Jim Brodie, Robb Krumlauf§ and David G. Wilkinson

Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
* Present address: Developmental and Molecular Biology of Animals, Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany
{dagger} Present address: The Sanger Centre, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK
{ddagger} Present address: Instituto Cajal, CSIC, Av. Doctor Arce 37, 28002 Madrid, Spain
§ Present address: Stowers Institute for Medical Research, 1000 East 50th, Kansas City, Missouri 64110, USA

¶Author for correspondence (e-mail: dwilkin{at}nimr.mrc.ac.uk)

Accepted 17 December 2001

Pattern formation in the hindbrain is governed by a segmentation process that provides the basis for the organisation of cranial motor nerves. A cascade of transcriptional activators, including the bZIP transcription factor encoded by the kreisler gene controls this segmentation process. In kreisler mutants, r5 fails to form and this correlates with abnormalities in the neuroanatomical organisation of the hindbrain. Studies of Hox gene regulation suggest that kreisler may regulate the identity as well as the formation of r5, but such a role cannot be detected in kreisler mutants since r5 is absent. To gain further insights into the function of kreisler we have generated transgenic mice in which kreisler is ectopically expressed in r3 and for an extended period in r5. In these transgenic mice, the Fgf3, Krox20, Hoxa3 and Hoxb3 genes have ectopic or prolonged expression domains in r3, indicating that it acquires molecular characteristics of r5. Prolonged kreisler expression subsequently causes morphological alterations of r3/r5 that are due to an inhibition of neuronal differentiation and migration from the ventricular zone to form the mantle layer. We find that these alterations in r5 correlate with an arrest of facial branchiomotor neurone migration from r4 into the caudal hindbrain, which is possibly due to the deficiency in the mantle layer through which they normally migrate. We propose that the requirement for the downregulation of segmental kreisler expression prior to neuronal differentiation reflects the stage-specific roles of this gene and its targets.

Key words: kreisler, Hindbrain, Segmentation, Neuronal differentiation, Migration, Mouse






© The Company of Biologists Ltd 2002