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1
MRC Intercellular Signalling Group, Centre for Developmental Genetics,
University of Sheffield School of Medicine and Biomedical Science, Firth
Court, Western Bank, Sheffield S10 2TN, UK
2
Department of Anatomy and Developmental Biology, University College London,
Gower Street, London WC1E 1BT, UK
3
Max-Planck Institut für Entwicklungsbiologie,
Spemannstrasse 36, 72076 Tübingen, Germany
*
Present address: Department of Biology, University of Konstanz, 78464
Konstanz, Germany
Present address: Department of Developmental and Cell Biology, University of
California at Irvine, Irvine, CA 92697-2300, USA
Author for correspondence (e-mail:
p.w.ingham{at}sheffield.ac.uk
)
Accepted 16 May 2001
We describe a new zebrafish mutation, neckless, and present
evidence that it inactivates retinaldehyde dehydrogenase type 2, an enzyme
involved in retinoic acid biosynthesis. neckless embryos are
characterised by a truncation of the anteroposterior axis anterior to the
somites, defects in midline mesendodermal tissues and absence of pectoral
fins. At a similar anteroposterior level within the nervous system, expression
of the retinoic acid receptor
and hoxb4 genes is
delayed and significantly reduced. Consistent with a primary defect in
retinoic acid signalling, some of these defects in neckless mutants
can be rescued by application of exogenous retinoic acid. We use mosaic
analysis to show that the reduction in hoxb4 expression in the
nervous system is a non-cell autonomous effect, reflecting a requirement for
retinoic acid signalling from adjacent paraxial mesoderm. Together, our
results demonstrate a conserved role for retinaldehyde dehydrogenase type 2 in
patterning the posterior cranial mesoderm of the vertebrate embryo and provide
definitive evidence for an involvement of endogenous retinoic acid in
signalling between the paraxial mesoderm and neural tube.
Key words: Zebrafish, Anteroposterior patterning, Vitamin A deficiency, Retinoic acid, Retinoic acid receptor, Craniofacial development, Neural crest, raldh2, hoxb4
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