The role of Hoxa-3 in mouse thymus and thyroid development

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 1989-2003 ◽  
Author(s):  
N.R. Manley ◽  
M.R. Capecchi
Keyword(s):  
Neural Crest ◽  
Posterior Part ◽  
Neural Crest Cell ◽  
Mutant Mice ◽  
Pharyngeal Pouch ◽  
Migration Patterns ◽  
Ultimobranchial Body ◽  
Embryonic Origin ◽  
Intrinsic Capacity ◽  
Or Genes

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.

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 ◽  
...  
Keyword(s):  
Neural Crest ◽  
Motor Neurons ◽  
Cranial Nerves ◽  
Three Dimensional ◽  
Neural Crest Cell ◽  
Mutant Mice ◽  
Morphological Data ◽  
Vagus Nerves ◽  
Membranous Labyrinth ◽  
Free Region

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.

scholarly journals Understanding neural crest cell development using Gcnf−/− mutant mice as a model system

2011 ◽  
Vol 356 (1) ◽  
pp. 185
Author(s):  
Annita Achilleos ◽  
Jennie Crane ◽  
Shachi Bhatt ◽  
Paul Trainor
Keyword(s):  
Neural Crest ◽  
Neural Crest Cell ◽  
Cell Development ◽  
Model System ◽  
Mutant Mice ◽  
Crest Cell

scholarly journals Abnormalities in neural crest cell migration in laminin α5 mutant mice

2006 ◽  
Vol 289 (1) ◽  
pp. 218-228 ◽  
Author(s):  
Edward G. Coles ◽  
Laura S. Gammill ◽  
Jeffrey H. Miner ◽  
Marianne Bronner-Fraser
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cell ◽  
Mutant Mice ◽  
Neural Crest Cell Migration ◽  
Crest Cell

scholarly journals P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus

2008 ◽  
Vol 295 (5) ◽  
pp. L858-L865 ◽  
Author(s):  
Kevin Kwong ◽  
Marian Kollarik ◽  
Christina Nassenstein ◽  
Fei Ru ◽  
Bradley J. Undem
Keyword(s):  
Guinea Pig ◽  
Neural Crest ◽  
Single Cell ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Receptor Activation ◽  
Rt Pcr ◽  
C Fibers ◽  
Embryonic Origin ◽  
Ganglion Neurons

The lungs and esophagus are innervated by sensory neurons with somata in the nodose, jugular, and dorsal root ganglion. These sensory ganglia are derived from embryonic placode (nodose) and neural crest tissues (jugular and dorsal root ganglia; DRG). We addressed the hypothesis that the neuron's embryonic origin (e.g., placode vs. neural crest) plays a greater role in determining particular aspects of its phenotype than the environment in which it innervates (e.g., lungs vs. esophagus). This hypothesis was tested using a combination of extracellular and patch-clamp electrophysiology and single-cell RT-PCR from guinea pig neurons. Nodose, but not jugular C-fibers innervating the lungs and esophagus, responded to α,β-methylene ATP with action potential discharge that was sensitive to the P2X3 (P2X2/3) selective receptor antagonist A-317491. The somata of lung- and esophagus-specific sensory fibers were identified using retrograde tracing with a fluorescent dye. Esophageal- and lung-traced neurons from placodal tissue (nodose neurons) responded similarly to α,β-methylene ATP (30 μM) with a large sustained inward current, whereas in neurons derived from neural crest tissue (jugular and DRG neurons), the same dose of α,β-methylene ATP resulted in only a transient rapidly inactivating current or no detectable current. It has been shown previously that only activation of P2X2/3 heteromeric receptors produce sustained currents, whereas homomeric P2X3 receptor activation produces a rapidly inactivating current. Consistent with this, single-cell RT-PCR analysis revealed that the nodose ganglion neurons innervating the lungs and esophagus expressed mRNA for P2X2 and P2X3 subunits, whereas the vast majority of jugular and dorsal root ganglia innervating these tissues expressed only P2X3 mRNA with little to no P2X2 mRNA expression. We conclude that the responsiveness of C-fibers innervating the lungs and esophagus to ATP and other purinergic agonists is determined more by their embryonic origin than by the environment of the tissue they ultimately innervate.

scholarly journals Proliferation dynamics associated with cranial neural crest cell migration

2011 ◽  
Vol 356 (1) ◽  
pp. 197
Author(s):  
Dennis A. Ridenour ◽  
Rebecca McLennan ◽  
Jessica M. Teddy ◽  
Katherine W. Prather ◽  
Craig L. Semerad ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cell ◽  
Cranial Neural Crest ◽  
Cranial Neural Crest Cell ◽  
Neural Crest Cell Migration ◽  
Crest Cell
Sign in / Sign up

Export Citation Format

Share Document