Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neural cell adhesion molecule (N-CAM) mediates cell-cell interactions and is expressed in characteristic spatiotemporal patterns during development. In previous studies of factors that control N-CAM gene expression, we identified a binding site for the paired domain of Pax proteins (designated PBS) in the mouse N-CAM promoter. In this study, we demonstrate that a transcription factor known to be important for development of the central nervous system, Pax-6, binds to the N-CAM PBS and show that the PBS can influence N-CAM expression in vivo. Pax-6, produced in COS-1 cells, bound to the PBS through two half-sites, PBS-1 and PBS-2; mutations in both of these sites completely disrupted binding. Moreover, nuclear extracts from embryonic day (E) 11.5 mouse embryos bound to the PBS, and this binding was inhibited by antibodies to Pax-6. To determine the role of the PBS in vivo, we generated transgenic mice with N-CAM promoter/lacZ gene constructs containing either a wild-type or a mutated PBS. Mutations in PBS-1 and PBS-2 decreased the extent of beta-galactosidase expression in the mantle layer of the spinal cord limiting it to ventral regions at E11.5. At E14.5, these mutations eliminated most of the expression that was seen in the wild-type spinal cord. Taken together with our previous observations that the PBS binds multiple Pax proteins, the data indicate that such binding contributes to the regulation of N-CAM gene expression during neural development.
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PMID:A binding site for Pax proteins regulates expression of the gene for the neural cell adhesion molecule in the embryonic spinal cord. 903 76

The cell adhesion molecule L1 regulates axonal guidance and fasciculation during development. We previously identified the regulatory region of the L1 gene and showed that it was sufficient for establishing the neural pattern of L1 expression in transgenic mice. In the present study, we characterize a DNA element within this region called the HPD that contains binding motifs for both homeodomain and Pax proteins and responds to signals from bone morphogenetic proteins (BMPs). An ATTA sequence within the core of the HPD was required for binding to the homeodomain protein Barx2 while a separate paired domain recognition motif was necessary for binding to Pax-6. In cellular transfection experiments, L1-luciferase reporter constructs containing the HPD were activated an average of 4-fold by Pax-6 in N2A cells and 5-fold by BMP-2 and BMP-4 in Ng108 cells. Both of these responses were eliminated on deletion of the HPD from L1 constructs. In transgenic mice, deletion of the HPD from an L1-lacZ reporter resulted in a loss of beta-galactosidase expression in the telencephalon and mesencephalon. Collectively, our experiments indicate that the HPD regulates L1 expression in neural tissues via homeodomain and Pax proteins and is likely to be a target of BMP signaling during development.
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PMID:A binding site for homeodomain and Pax proteins is necessary for L1 cell adhesion molecule gene expression by Pax-6 and bone morphogenetic proteins. 1005 57

Gonadotropin-releasing hormone-I (GnRH-I) is thought to be expressed by a single, highly spatially restricted group of neurons, which originate in the olfactory placode and migrate through the nose into the medial septum and hypothalamus from where they control fertility. Transgenic mice bearing a 13.5 kb GnRH-I-lacZ reporter construct were derived and found to express high levels of beta-galactosidase mRNA and protein within the septohypothalamic GnRH neurons in a correct temporal and spatial manner. Unexpectedly, low levels of beta-galactosidase were also present in three further populations of cells within the lateral septum, bed nucleus of the stria terminalis, and tectum. Analysis of wild-type mice with three different GnRH-I antibodies revealed distinct and transient patterns of GnRH-I peptide expression during development in all three of these populations revealed by transgenics. The synthesis of GnRH by cells of the lateral septum was the most persistent and remained until the third postnatal week. Embryonic "small eye" Pax-6 null mice, which fail to develop an olfactory placode, were also examined and shown to have equivalent populations of GnRH-I-immunoreactive cells in the lateral septum, tectum, and bed nucleus of the stria terminalis but none of the migrating cells that form the septohypothalamic GnRH population. These results prove that so-called "ectopic" expression in promoter transgenic lines can reflect authentic developmental patterns of gene expression. They further provide the first demonstration in mammalian brain that multiple neuronal populations of different embryological origin express GnRH-I peptide during embryonic and postnatal development.
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PMID:Promoter transgenics reveal multiple gonadotropin-releasing hormone-I-expressing cell populations of different embryological origin in mouse brain. 1040 34

Expression of Pax-2 in the mouse gastrula is the first marker of the midbrain-hindbrain region. To address roles played by transcription factors in the process of neural plate pattern formation and to facilitate gain-of-function approaches in the study of midbrain-hindbrain and cerebellar development, we characterized regulatory sequences at the Pax-2 locus using an in vivo transgenic mouse reporter assay. An 8.5 kb fragment of genomic DNA located upstream of Pax-2 directed lacZ expression prior to neurulation (7.5 days post-coitum, dpc) in a region fated to become midbrain and hindbrain, and subsequently in developing neuroepithelium. While similar to the pattern of Pax-2 expression, reporter gene activity extended beyond the boundaries of Pax-2 expression, most probably reflecting purdurance of beta-galactosidase activity and an absence of DNA sequences that restrict Pax-2 expression to rhombomere 1 by 9. 5 dpc. In the fetal and neonatal brain, Pax-2-lacZ activity was confined largely to Purkinje cells and the external granule cell layer (EGL) of the cerebellum. A 4 kb regulatory element, in contrast, initiated neural expression at 8.25 dpc in the anterior hindbrain, but recapitulated all later aspects of Pax-2-lacZ activity observed with the larger transgene. These results indicate the presence of regulatory sequences upstream of the Pax-2 locus capable of directing gene expression in the developing midbrain, first rhombomere of the hindbrain, and its principal derivative, the cerebellum. Successful misexpression of Sonic hedgehog demonstrates that Pax-2 regulatory sequences should prove generally useful for transgenic gain-of-function approaches in mice.
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PMID:Pax-2 regulatory sequences that direct transgene expression in the developing neural plate and external granule cell layer of the cerebellum. 1053 37

The vitamin A derivative retinoic acid (RA) is necessary for eye development, though its role in signaling within eye tissues is poorly understood. We investigated this question in two transgenic mouse strains carrying a retinoic acid response element (RARE) fused to beta-galactosidase that identify regions of the embryo expressing activated retinoic acid receptors. Retinoid signaling appears in the retina and lens ectoderm of wild-type embryos prior to neural tube closure, when lens induction is under way. To determine if there are interactions between retinoid signaling and the transcription factor Pax-6, also essential for lens development, we examined RARE transgene expression in Small eye (Sey) mice, which carry a Pax-6 mutation. Retinoid signaling in the eye, nose, and forebrain of Sey embryos is decreased, with the most severe effects in the developing lens. In Sey mice the lens anlage cannot respond to exogenous RA after E9, though it is responsive earlier; the retina and other neural ectoderm can respond to RA at any stage. In Sey mice the ability of presumptive lens and retina to produce and/or sequester RA is also decreased, as assayed with a retinoid-reporter cell line. These results implicate retinoid signaling in lens formation and show that RA signaling in the developing eye is dependent upon Pax-6.
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PMID:Altered retinoid signaling in the heads of small eye mouse embryos. 1077 88

Six genes are widely expressed during vertebrate embryogenesis, suggesting that they are implicated in diverse differentiation processes. To determine the functions of the Six1 gene, we constructed Six1-deficient mice by replacing its first exon by the beta-galactosidase gene. We have previously shown that mice lacking Six1 die at birth due to thoracic skeletal defects and severe muscle hypoplasia affecting most of the body muscles. Here, we report that Six1(-/-) neonates also lack a kidney and thymus, as well as displaying a strong disorganisation of craniofacial structures, namely the inner ear, the nasal cavity, the craniofacial skeleton, and the lacrimal and parotid glands. These organ defects can be correlated with Six1 expression in the embryonic primordium structures as revealed by X-Gal staining at different stages of embryogenesis. Thus, the fetal abnormalities of Six1(-/-) mice appear to result from the absence of the Six 1 homeoprotein during early stages of organogenesis. Interestingly, these Six1 defects are very similar to phenotypes caused by mutations of Eya 1, which are responsible for the BOR syndrome in humans. Close comparison of Six1 and Eya 1 deficient mice strongly suggests a functional link between these two factors. Pax gene mutations also lead to comparable phenotypes, suggesting that a regulatory network including the Pax, Six and Eya genes is required for several types of organogenesis in mammals.
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PMID:Thymus, kidney and craniofacial abnormalities in Six 1 deficient mice. 1283 66

The metanephric kidney is a mesodermal organ that develops as a result of reciprocal interactions between the ureteric bud and the blastema. The generation of embryonic stem (ES) cell-derived progenitors offers potential for regenerative therapies but is often limited by development of tumor formation. Because brachyury (T) denotes mesoderm specification, a mouse ES cell line with green fluorescence protein (GFP) knocked into the functional T locus as well as lacZ in the ROSA26 locus (LacZ/T/GFP) was used in cell selection and lineage tracing. In the absence of leukemia inhibitory factor, mouse ES cells give rise to embryoid bodies that can differentiate into mesoderm. Culture conditions were optimized (4 d, 10 ng/ml Activin-A) to generate maximal numbers of renal progenitor populations identified by expression of the specific combination of renal markers cadherin-11, WT-1, Pax-2, and Wnt-4. LacZ/T/GFP+ cells were further enriched by FACS selection. Five days after injection of LacZ/T/GFP+ cells into embryonic kidney explants in organ culture, beta-galactosidase immunohistochemistry showed incorporation into blastemal cells of the nephrogenic zone. After a single injection into developing live newborn mouse kidneys, co-localization studies showed that the LacZ/T/GFP+ cells were stably integrated into proximal tubules with normal morphology and normal polarization of alkaline phosphatase and aquaporin-1 for 7 mo, without teratoma formation. It is concluded that defined differentiation of ES cells into embryoid bodies with Activin-A and selection for T expression provides a means to isolate and purify renal proximal tubular progenitor cells with the potential for safe use in regenerative therapies.
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PMID:Mouse embryonic stem cell-derived embryoid bodies generate progenitors that integrate long term into renal proximal tubules in vivo. 2199 95

Expression and function of the transcription factor Sox10 is predominant in neural crest cells, its derivatives and in oligodendrocytes. To understand how Sox10 expression is regulated during development, we analysed the potential of evolutionary conserved non-coding sequences in the Sox10 genomic region to function as enhancers. By linking these sequences to a beta-galactosidase marker gene under the control of a minimal promoter, five regulatory regions were identified that direct marker gene expression in transgenic mice to Sox10 expressing cell types and tissues in a defined temporal pattern. These possible enhancers of the Sox10 gene mediate Sox10 expression in the otic vesicle, in oligodendrocytes and in several neural crest derivatives including the developing peripheral nervous system and the adrenal gland. They furthermore exhibit overlapping activities and share binding sites for Sox, Lef/Tcf, Pax and AP2 transcription factors. This may explain high level and robustness of Sox10 expression during embryonic development.
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PMID:Multiple conserved regulatory elements with overlapping functions determine Sox10 expression in mouse embryogenesis. 1789 62