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JOURNAL ARTICLES
Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch
A. Gavalas, M. Studer, A. Lumsden, F.M. Rijli, R. Krumlauf, P. Chambon
Development 1998 125: 1123-1136;

Summary

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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JOURNAL ARTICLES
Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch
A. Gavalas, M. Studer, A. Lumsden, F.M. Rijli, R. Krumlauf, P. Chambon
Development 1998 125: 1123-1136;
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An extract from a schematic demonstrating the possible pipeline for how discovery in lab model systems can influence applications for regenerative therapies.

One of the most challenging objectives of tissue regeneration research is regrowth of a lost or amputated limb. Here, Ben Cox, Maximina Yun and Kenneth Poss outline the research avenues yet to be explored to move closer to this capstone achievement.

Articles of interest in our sister journals

Tox4 modulates cell fate reprogramming

Lotte Vanheer, Juan Song, Natalie De Geest, Adrian Janiszewski, Irene Talon, Caterina Provenzano, Taeho Oh, Joel Chappell, Vincent Pasque
Journal of Cell Science

Drosophila melanogaster: a simple system for understanding complexity

Stephanie E. Mohr, Norbert Perrimon
Disease Models & Mechanisms