Here we define the expression of ∼100 transcription factors in progenitors and neurons of the developing basal ganglia. We have begun to elucidate the transcriptional hierarchy of these genes with respect to the Dlx homeodomain genes, which are essential for differentiation of most GABAergic projection neurons of the basal ganglia. This analysis identified Dlx-dependent and Dlx-independent pathways. The Dlx-independent pathway depends in part on the function of the Mash1 b-HLH transcription factor. These analyses define core transcriptional components that differentially specify the identity and differentiation of the striatum, nucleus accumbens and septum.

Genome-wide expression profiling has aided the understanding of the molecular basis of neuronal diversity, but achieving broad functional insight remains a considerable challenge. Here, we perform the first systems-level analysis of microarray data from single neuronal populations using weighted gene co-expression network analysis to examine how neuronal transcriptome organization relates to neuronal function and diversity. We systematically validate network predictions using published proteomic and genomic data. Several network modules of co-expressed genes correspond to interneuron development programs, in which the hub genes are known to be critical for interneuron specification. Other co-expression modules relate to fundamental cellular functions, such as energy production, firing rate, trafficking, and synapses, suggesting that fundamental aspects of neuronal diversity are produced by quantitative variation in basic metabolic processes. We identify two transcriptionally distinct mitochondrial modules and demonstrate that one corresponds to mitochondria enriched in neuronal processes and synapses, whereas the other represents a population restricted to the soma. Finally, we show that galectin-1 is a new interneuron marker, and we validate network predictions in vivo using Rgs4 and Dlx1/2 knockout mice. These analyses provide a basis for understanding how specific aspects of neuronal phenotypic diversity are organized at the transcriptional level.

Gonadotropin-releasing hormone (GnRH) is the central regulator of the hypothalamic-pituitary-gonadal axis, controlling sexual maturation and fertility in diverse species from fish to humans. GnRH gene expression is limited to a discrete population of neurons that migrate through the nasal region into the hypothalamus during embryonic development. The GnRH regulatory region contains four conserved homeodomain binding sites (ATTA) that are essential for basal promoter activity and cell-specific expression of the GnRH gene. MSX and DLX are members of the Antennapedia class of non-Hox homeodomain transcription factors that regulate gene expression and influence development of the craniofacial structures and anterior forebrain. Here, we report that expression patterns of the Msx and Dlx families of homeodomain transcription factors largely coincide with the migratory route of GnRH neurons and co-express with GnRH in neurons during embryonic development. In addition, MSX and DLX family members bind directly to the ATTA consensus sequences and regulate transcriptional activity of the GnRH promoter. Finally, mice lacking MSX1 or DLX1 and 2 show altered numbers of GnRH-expressing cells in regions where these factors likely function. These findings strongly support a role for MSX and DLX in contributing to spatiotemporal regulation of GnRH transcription during development.Proper sexual maturation and fertility are dependent upon the correct function of the hypothalamic-pituitary-gonadal axis, initiated by a small, yet critical population of gonadotropin-releasing hormone (GnRH) 1 neurons. The GnRH gene is expressed in a complex spatiotemporal manner during embryonic development and into postnatal life with several populations of GnRH-expressing neurons originating at different developmental stages and locations. These populations include the classical, septohypothalamic neurons, as well as populations in the lateral septum, posterior bed nucleus stria terminalis (pBNST), and tectum (1, 2). Although the role of each of these populations of GnRH-producing neurons remains to be elucidated, the contribution of the septohypothalamic population is required for maturation of the hypothalamic-pituitarygonadal axis and fertility (3).The precursor cells of the septohypothalamic GnRH neurons have been reported to originate within the olfactory placode (4 -6) or the neural crest (7) and begin to express the GnRH transcript in a discrete population of cells located in close proximity to the olfactory placode of the embryonic mouse by 11.5-days postcoitum (11.5 dpc). By 12.5 dpc, the full complement of septohypothalamic GnRH neurons (ϳ800) in the adult population is established (6), and over the course of the next several days, these neurons migrate toward the CNS, closely associated with the established position of the peripherin-positive nerve bundle of the olfactory nerve (8, 9). By 16.5 dpc the majority of the septohypothalamic neurons have reached their destination, scattered throughout the preoptic area, the diagonal band of Broc...

The tobacco gene g10 is preferentially and maximally expressed in mature pollen, shows homology to pectate lyases, and is the putative homologue of the tomato gene lat56. Analysis of regulatory elements within the g10 promoter was carried out to verify the importance of putative regulatory sequence motifs. Analysis of transgenic plants showed that 1190 bp of g10 5' sequence directed preferential expression of GUS in pollen, with bimodal peaks of expression just before and during pollen mitosis I, and in mature anthers. This was confirmed by northern analysis of native g10 transcripts in isolated spores. Transient expression analysis defined the minimal g10 promoter region capable of directing expression in pollen as -86 to +217. Three upstream regions within -427 bp modulate the expression from g10. Gain-of-function analyses showed that the region from -106 to -53 could enhance pollen-specific expression of a minimal CaMV 35S promoter. These analyses further showed that sequences upstream of -86 modulate expression in pollen, but are not essential for preferential pollen expression. The function of a conserved GTGA motif shared between the tobacco g10 and tomato lat56 promoters was demonstrated in g10. Thus, further functional evidence is provided for the conservation of mechanisms for the regulation of late pollen genes across species.

Subjects with thicker anterior mitral leaflets and more severe MR were more likely to receive two MitraClip devices. Immediate and long-term reduction in MR was similar regardless of the number of devices implanted at the time of the procedure.

No abstract

No abstract