Two rhombomeres are altered in Hoxa-1 mutant mice

Development ◽  
1993 ◽  
Vol 119 (2) ◽  
pp. 319-338 ◽  
Author(s):  
M. Mark ◽  
T. Lufkin ◽  
J.L. Vonesch ◽  
E. Ruberte ◽  
J.C. Olivo ◽  
...  

This study provides a detailed description of the anatomical defects in the Hoxa-1−/− mutant mice previously generated in our laboratory (T. Lufkin, A. Dierich, M. LeMeur, M. Mark and P. Chambon, 1991; Cell 66, 1105–1119). Three-dimensional reconstructions of the Hoxa-1−/− rhombencephalon reveals that it bears only five rhombomeric structures (ie. morphological segments) instead of the normal seven. The first three of these rhombomeres appear normal as judged from the distribution pattern of CRABPI transcripts in the neurectoderm and from the histological analysis of the cranial nerve components derived from these structures. In contrast, the neural-crest-cell-free region normally located opposite rhombomere 5 is lacking in Hoxa-1−/− embryos, and motor neurons of the facial and abducens nerves, which normally differentiate within rhombomeres 4, 5 and 6, are missing in Hoxa-1−/− fetuses. These morphological data, combined with the determination of the molecular positional identities of the rhombomeres 4 and 5 (P. Dolle, T. Lufkin, R. Krumlauf, M. Mark, D. Duboule and P. Chambon, 1993; Proc. Natl. Acad. Sci. USA, in press), suggest that rhombomere 4 is markedly reduced, whereas rhombomere 5 is almost absent. Thus, the remnants of rhombomeres 4 and 5 appear to be fused caudally with rhombomere 6 to form a single fourth rhombomeric structure. Moreover, the migration of neural crest cells contributing to the glossopharyngeal and vagus nerves occurs in a more rostral position, resulting in abnormalities of these cranial nerves, which were visualized by whole-mount anti-neurofilament immunostaining. The mutual relationship along the rostrocaudal axis between the otic pit and the neuroepithelial site of int-2 protein secretion (a putative otogenic cue) is not significantly changed in Hoxa-1−/− embryos. However, the abnormal relationship between the rhombencephalon and the epithelial inner ear may account for the aplasia and faulty differentiation of the membranous labyrinth, the disruption of the cartilaginous otic capsule and the disorganisation of some middle ear structures. This phenotype is compared with that of the Hoxa-1−/− mutants generated by O. Chisaka, T. S. Musci and M. R. Capecchi, 1992 (Nature 335, 516–520) and with that of the mice homozygous for the kreisler mutation.

2011 ◽  
Vol 356 (1) ◽  
pp. 185
Author(s):  
Annita Achilleos ◽  
Jennie Crane ◽  
Shachi Bhatt ◽  
Paul Trainor

2006 ◽  
Vol 289 (1) ◽  
pp. 218-228 ◽  
Author(s):  
Edward G. Coles ◽  
Laura S. Gammill ◽  
Jeffrey H. Miner ◽  
Marianne Bronner-Fraser

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 1989-2003 ◽  
Author(s):  
N.R. Manley ◽  
M.R. Capecchi

Targeted disruption of Hoxa-3 results in a number of regionally restricted defects in tissues and structures derived from or patterned by mesenchymal neural crest. However, analysis of mutant embryos with injections of a carbocyanine dye or with molecular markers that label these cells indicates that neither the amount nor the migration patterns of this neural crest population are grossly affected. Therefore, it appears that the loss of Hoxa-3 affects the intrinsic capacity of this neural crest cell population to differentiate and/or to induce proper differentiation of the surrounding pharyngeal arch and pouch tissues. Hoxa-3 mutant mice are athymic and show thyroid hypoplasia. Thymus development is first evident as an expansion of mesenchymal neural crest in the posterior part of the 3rd pharyngeal pouch. Prior to this expansion, a marked reduction in pax-1 expression is observed in these cells in the mutant embryos. As pax-1 mutant mice also show thymic hypoplasia, these results suggest that Hoxa-3 may be required to maintain pax-1 expression in these cells and that the reduction of pax-1 expression is part of the athymic teleology in Hoxa-3 mutant mice. The thyroid gland is formed from the fusion of two structures of separate embryonic origin, the thyroid diverticulum, which is formed from endodermal epithelium in the floor of the pharynx, and the ultimobranchial body, formed from mesenchymal neural crest in the 4th pharyngeal pouch. Both of these sites express Hoxa-3 and are defective in mutant mice. Often a vesicle is observed in mutant mice that is exclusively composed of calcitonin-producing cells, suggesting the persistence of an ultimobranchial body. Both aspects of the thyroid phenotype show variable expressivity among mutant animals, even on the two sides of the same mutant animal. This variability suggests the presence of a compensating gene or genes, whose utilization is stochastic. A reasonable candidate for providing this compensatory function is the paralogous gene Hoxb-3.


Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 1123-1136 ◽  
Author(s):  
A. Gavalas ◽  
M. Studer ◽  
A. Lumsden ◽  
F.M. Rijli ◽  
R. Krumlauf ◽  
...  

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.


Author(s):  
O. Faroon ◽  
F. Al-Bagdadi ◽  
T. G. Snider ◽  
C. Titkemeyer

The lymphatic system is very important in the immunological activities of the body. Clinicians confirm the diagnosis of infectious diseases by palpating the involved cutaneous lymph node for changes in size, heat, and consistency. Clinical pathologists diagnose systemic diseases through biopsies of superficial lymph nodes. In many parts of the world the goat is considered as an important source of milk and meat products.The lymphatic system has been studied extensively. These studies lack precise information on the natural morphology of the lymph nodes and their vascular and cellular constituent. This is due to using improper technique for such studies. A few studies used the SEM, conducted by cutting the lymph node with a blade. The morphological data collected by this method are artificial and do not reflect the normal three dimensional surface of the examined area of the lymph node. SEM has been used to study the lymph vessels and lymph nodes of different animals. No information on the cutaneous lymph nodes of the goat has ever been collected using the scanning electron microscope.


Lab on a Chip ◽  
2021 ◽  
Author(s):  
Kazuki Yamamoto ◽  
Nao Yamaoka ◽  
Yu Imaizumi ◽  
Takunori Nagashima ◽  
Taiki Furutani ◽  
...  

A three-dimensional human neuromuscular tissue model that mimics the physically separated structures of motor neurons and skeletal muscle fibers is presented.


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