Selective requirement of Pax6, but not Emx2, in the specification and development of several nuclei of the amygdaloid complex.
ABSTRACT The amygdaloid complex is a group of nuclei that are thought to originate from multiple sites of the dorsal and ventral telencephalic neuroepithelium. The mechanisms that regulate their development are essentially unknown. We studied the role of Pax6 and Emx2, two transcription factors that regulate regional specification and growth of the telencephalon, in the morphogenesis of the amygdaloid complex. We used a set of specific marker genes that identify distinct amygdaloid nuclei to analyze Pax6/Small eye and Emx2 knock-out mutant mouse brains. We found that there is a selective requirement for Pax6, but not Emx2, in the formation a subset of nuclei within the amygdaloid complex. Specifically, structures that were not previously considered to be developmentally linked, the nucleus of the lateral olfactory tract and the lateral, basolateral, and basomedial nuclei, all appear to have a common requirement for Pax6. Together, our findings provide new insights into the origins and mechanisms underlying the development of the amygdaloid complex.
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ABSTRACT: Many of the genes involved in brain patterning during development are highly conserved in vertebrates and similarities in their expression patterns help to recognize homologous cell types or brain regions. Among these genes, Pax6 and Pax7 are expressed in regionally restricted patterns in the brain and are essential for its development. In the present immunohistochemical study we analyzed the distribution of Pax6 and Pax7 cells in the brain of six representative species of tetrapods and lungfishes, the closest living relatives of tetrapods, at several developmental stages. The distribution patterns of these transcription factors were largely comparable across species. In all species only Pax6 was expressed in the telencephalon, including the olfactory bulbs, septum, striatum, and amygdaloid complex. In the diencephalon, Pax6 and Pax7 were distinct in the alar and basal parts, mainly in prosomeres 1 and 3. Pax7 specifically labeled cells in the optic tectum (superior colliculus) and Pax6, but not Pax7, cells were found in the tegmentum. Pax6 was found in most granule cells of the cerebellum and Pax7 labeling was detected in cells of the ventricular zone of the rostral alar plate and in migrated cells in the basal plate, including the griseum centrale and the interpeduncular nucleus. Caudally, Pax6 cells formed a column, whereas the ventricular zone of the alar plate expressed Pax7. Since the observed Pax6 and Pax7 expression patterns are largely conserved they can be used to identify subdivisions in the brain across vertebrates that are not clearly discernible with classical techniques.Frontiers in Neuroanatomy 08/2014; 8(75):1-20. · 4.06 Impact Factor
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ABSTRACT: The subpallium comprises large parts of the basal ganglia including striatum and globus pallidus. Genes and factors involved in the development of the subpallium have been extensively studied in most vertebrates, including amphibians, birds, and rodents. However, our knowledge on patterning of the human subpallium remains insufficient. Using double fluorescent immunohistochemistry, we investigated the protein distribution of transcription factors involved in patterning of the subventricular zone (SVZ) in the human forebrain at late embryonic development. Furthermore, we compared the development of cortical and striatal precursors between human fetal brain and E14 and E16 fetal rat brains. Our results reveal that DLX2 marks SVZ precursors in the entire subpallium. Individual subpallial subdomains can be identified based on co-expression of DLX2 with either PAX6 or NKX2-1. SVZ precursors in the dorsal LGE and preopto-hypothalamic boundary are characterized by DLX2/PAX6 co-expression, while precursors in the MGE and preoptic region co-express DLX2/NKX2-1. SVZ precursors in the ventral LGE are DLX2(+)/PAX6(-)/NKX2-1(-). In terms of staging comparisons, the development of the corpus striatum in the human fetal brain during late embryonic stages corresponds well with the development of the striatum observed in E14 fetal rat brains. Our study demonstrates that the pattern underlying the development of the subpallium is highly conserved between rodents and humans and suggests a similar function for these factors in human brain development. Moreover, our data directly influence the application of ganglionic eminence derived human tissue for cell therapeutic approaches in neurodegenerative disorders such as Huntington's disease.Frontiers in Neuroanatomy 01/2013; 7:54. · 4.06 Impact Factor
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ABSTRACT: Background. The basolateral complex, comprised of the lateral, basolateral, and basomedial nuclei, is the main structure of the amygdala and contains two neuronal cell types: excitatory neurons and inhibitory interneurons. Studies show that most of the excitatory neurons originate in the ventral pallium of the telencephalon. However, their subsequent development remains poorly understood.Results. In this study, we examined the roles of the zinc finger gene Fezf2 in the development of the amygdala. Fezf2 is expressed in the lateral and basolateral nuclei during development. In Fezf2-deficient embryos, specific excitatory neuron markers in the lateral and basolateral nuclei were reduced, with concurrent induction of other markers in the endopiriform cortex. Furthermore, the morphology of the lateral and basolateral nuclei was abnormal. In the adult stages, excitatory neurons in the lateral and basolateral nuclei were greatly reduced because of apoptosis that occurred soon after birth.Conclusions. These results suggest that Fezf2 is required for the development of excitatory neurons and nuclear morphology in the lateral and basolateral nuclei, and that abnormal formation of these regions leads to cell death soon after birth in Fezf2-deficient mice. Developmental Dynamics, 2014. © 2014 Wiley Periodicals, Inc.Developmental Dynamics 04/2014; · 2.59 Impact Factor