RESUMO
In vertebrates, the proximal and distal sensory ganglia of the branchial nerves are derived from neural crest cells (NCCs) and placodes, respectively. We previously reported that in Hoxa3 knockout mouse embryos, NCCs and placode-derived cells of the glossopharyngeal nerve were defective in their migration. In this report, to determine the cell-type origin for this Hoxa3 knockout phenotype, we blocked the expression of the gene with antisense morpholino oligonucleotides (MO) specifically in either NCCs/neural tube or placodal cells of chicken embryos. Our results showed that HOXA3 function was required for the migration of the epibranchial placode-derived cells and that HOXA3 regulated this cell migration in both NCCs/neural tube and placodal cells. We also report that the expression pattern of chicken HOXA3 was slightly different from that of mouse Hoxa3.
Assuntos
Movimento Celular/genética , Proteínas de Homeodomínio/genética , Crista Neural/metabolismo , Animais , Embrião de Galinha , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Camundongos , Crista Neural/citologia , Crista Neural/embriologia , RNA Mensageiro/metabolismo , Rombencéfalo/citologia , Rombencéfalo/embriologia , Rombencéfalo/metabolismoRESUMO
During nervous system development, a small number of conserved guidance cues and receptors regulate many axon trajectories. How could a limited number of cues and receptors regulate such complex projection patterns? One way is to modulate receptor function. Here we show that the Caenorhabditis elegans kinesin-related protein VAB-8L, which is necessary and sufficient for posterior cell and growth-cone migrations, directs these migrations by regulating the levels of the guidance receptor SAX-3 (also known as robo). Genetic experiments indicate that VAB-8L and the Rac guanine nucleotide exchange factor activity of UNC-73 (trio) increase the ability of the SLT-1 (slit) and UNC-6 (netrin) guidance pathways to promote posterior guidance. The observations of higher SAX-3 receptor abundance in animals with increasing amounts of VAB-8L, and of physical interactions between UNC-73 and both VAB-8L and the intracellular domain of the SAX-3, support a model whereby VAB-8L directs cell and growth-cone migrations by promoting localization of guidance receptors to the cell surface.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Movimento Celular/fisiologia , Cones de Crescimento/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Sistema Nervoso/embriologia , Receptores Imunológicos/metabolismo , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Diferenciação Celular/fisiologia , Sinais (Psicologia) , Cones de Crescimento/ultraestrutura , Proteínas do Tecido Nervoso/genética , Sistema Nervoso/citologia , Sistema Nervoso/metabolismo , Netrinas , Receptores Imunológicos/genética , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas RoundaboutRESUMO
Homeobox gene Hoxa3 is expressed in the third pharyngeal arch and pouch and is required for development of the third arch artery in addition to the thymus, parathyroid gland and carotid body. We therefore statistically analyzed malformations of the carotid artery system in Hoxa3 homozygous mutant mice, in comparison with wild-type and heterozygous littermates. To identify the carotid artery system, red carbon ink was injected, or vascular casts were made by injection of Mercox resin and observed by scanning electron microscopy. Furthermore, innervation of the carotid sinus and baroreceptor regions in the aortic arch and right subclavian artery were studied in the Hoxa3 null mutants having an abnormal carotid artery system by immunohistochemistry with TuJ1 and protein gene product (PGP) 9.5 antibodies, which recognize nerve fibers and neurons. The common carotid artery of Hoxa3 homozygous mutants was absent or very short and therefore the internal and external carotid artery arose from a more proximal level than those of wild types. The baroreceptor innervation, however, persisted in the mutants, although vascular targets were changed. These results indicate that Hoxa3 gene is crucial for the formation of the common carotid artery and the null mutant mice are the first useful animal models to show that the third arch arteries on both sides specifically degenerate but the fourth and sixth arch arteries are normal.