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Gavalas, A.* ; Studer, M.* ; Lumsden, A.* ; Rijli, F.M.* ; Krumlauf, R.* ; Chambon, P.*

Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch.

Development 125, 1123-1136 (1998)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The analysis of Hoxa1 and Hoxb1 null mutants suggested that these genes are involved in distinct aspects of hindbrain segmentation and specification. Here we investigate the possible functional synergy of the two genes. The generation of Hoxa1(3'RARE)/Hoxb1(3'RARE) compound mutants resulted in mild facial motor nerve defects reminiscent of those present in the Hoxb1 null mutants. Strong genetic interactions between Hoxa1 and Hoxb1 were uncovered by introducing the Hoxb1(3'RARE) and Hoxb1 null mutations into the Hoxa1 null genetic background. Hoxa1(null)/Hoxb1(3'RARE) and Hoxa1(null)/Hoxb1(null )double homozygous embryos showed additional patterning defects in the r4-r6 region but maintained a molecularly distinct r4-like territory. Neurofilament staining and retrograde labelling of motor neurons indicated that Hoxa1 and Hoxb1 synergise in patterning the VIIth through XIth cranial nerves. The second arch expression of neural crest cell markers was abolished or dramatically reduced, suggesting a defect in this cell population. Strikingly, the second arch of the double mutant embryos involuted by 10.5 dpc and this resulted in loss of all second arch-derived elements and complete disruption of external and middle ear development. Additional defects, most notably the lack of tympanic ring, were found in first arch-derived elements, suggesting that interactions between first and second arch take place during development. Taken together, our results unveil an extensive functional synergy between Hoxa1 and Hoxb1 that was not anticipated from the phenotypes of the simple null mutants.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 1998
HGF-reported in Year 0
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Quellenangaben Volume: 125, Issue: 6, Pages: 1123-1136 Article Number: , Supplement: ,
Publisher Company of Biologists
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502600-003
PubMed ID 9463359
Erfassungsdatum 1998-12-31