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)

Studies of cell lineage in the rat cerebral cortex have provided new insights into the mechanisms of neuronal and glial determination. They have shown that clonally related cells, marked with retrovirus injection at embryonic day 16 (E16), express the same glial or neuronal phenotype, suggesting that separate progenitors for each of these cell phenotypes exist in the ventricular zone at that stage of corticogenesis. However, it is not known if such committed progenitors are present in the ventricular zone before E16. Another important question concerns which neurochemical features are shared by clonally related cells of the adult cerebral cortex. In this study we have addressed the first question by injecting a retroviral vector expressing beta-galactosidase into the telencephalic ventricles of rat embryos at different stages (E14-E19). In order to classify clonally related neurons in the cerebral cortex of these rats, we have used postembedding immunohistochemistry for the amino acid neurotransmitters glutamate, aspartate, and GABA. Glutamate and GABA immunoreactivity marked nonoverlapping populations of cells that corresponded to the pyramidal and nonpyramidal neuron types of the rat cerebral cortex. Clonally related neurons, marked by retrovirus injection at any day between E14 and E19, homogeneously expressed one or other phenotype and accordingly displayed glutamate or GABA immunoreactivity. This finding indicates that committed progenitor cells for pyramidal and nonpyramidal neurons are present in the ventricular zone before E16. To investigate whether lineage dictates other features in clonally related neurons, we performed an immunohistochemical analysis for the calcium-binding proteins calbindin, parvalbumin, and calretinin in clusters of clonally related nonpyramidal neurons. The same calcium-binding protein was rarely found in members of the same cluster, suggesting that lineage does not control the expression of calcium-binding proteins in cortical nonpyramidal neurons. As a result of examining a large number of clonally related neurons from brains injected at different ages, we observed remarkable differences in number and laminar distribution of pyramidal and nonpyramidal neurons marked with retrovirus. Clusters of nonpyramidal neurons were usually composed of two or three cells, and resided in the cortical layers that were just being generated at the time of injection. Clusters of pyramidal neurons were larger and dispersed in several layers in the earlier injections; their size and laminar distribution were progressively reduced for later injections. These observations suggest the existence of different mechanisms that generate the pyramidal and nonpyramidal neurons of the cerebral cortex.
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PMID:Lineage analysis reveals neurotransmitter (GABA or glutamate) but not calcium-binding protein homogeneity in clonally related cortical neurons. 790 3

During development of the vertebrate nervous system, the neural cell adhesion molecule (N-CAM) is expressed in a defined spatiotemporal pattern. We have proposed that the expression of N-CAM is controlled, in part, by proteins encoded by homeobox genes. This hypothesis has been supported by previous in vitro experiments showing that products of homeobox genes can both bind to and transactivate the N-CAM promoter via two homeodomain binding sites, HBS-I and HBS-II. We have now tested the hypothesis that the N-CAM gene is a target of homeodomain proteins in vivo by using transgenic mice containing native and mutated N-CAM promoter constructs linked to a beta-galactosidase reporter gene. Segments of the 5' flanking region of the mouse N-CAM gene were sufficient to direct expression of the reporter gene in the central nervous system in a pattern consistent with that of the endogenous N-CAM gene. For example, at embryonic day (E) 11, beta-galactosidase staining was found in postmitotic neurons in dorsolateral and ventrolateral regions of the spinal cord; at E14.5, staining was seen in these neurons throughout the spinal cord. In contrast, mice carrying an N-CAM promoter-reporter construct with mutations in both homeodomain binding sites (HBS-I and HBS-II) showed altered expression patterns in the spinal cord. At E11, beta-galactosidase expression was seen in the ventrolateral spinal cord, but was absent in the dorsolateral areas, and at E 14.5, beta-galactosidase expression was no longer detected in any cells of the cord. Homeodomain binding sites found in the N-CAM promoter thus appear to be important in determining specific expression patterns of N-CAM along the dorsoventral axis in the developing spinal cord. These experiments suggest that the N-CAM gene is an in vivo target of homeobox gene products in vertebrates.
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PMID:Embryonic expression patterns of the neural cell adhesion molecule gene are regulated by homeodomain binding sites. 870 Aug 54

We have studied the lineage relationships of pyramidal and nonpyramidal neurons, the principal neuronal types in the cerebral cortex, using a recombinant retrovirus that carries the gene encoding Escherichia coli beta-galactosidase as a lineage marker. The phenotype of every cell of clones of beta-galactosidase-labelled neurons generated by intraventricular injection of recombinant retrovirus in rat embryos at different stages of cortical neurogenesis was identified using light and electron microscopy as well as immunohistochemistry for known markers of neuronal subtypes. We found that clonally related neurons in adult rats showed the same morphological and neurotransmitter phenotypes, suggesting that lineages of pyramidal and nonpyramidal neurons are specified as early as E14, the time of onset of neurogenesis. However, when we followed the development of cortical cell lineages, we noted that a significant number of neuronal clones showed a mixed pyramidal/nonpyramidal cell composition during the first three weeks of life. We suggest that the change in the composition of neuronal clones between the third week of postnatal life and adulthood may either be due to changes in the phenotype of some developing neurons or, more likely, to selective cell death.
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PMID:The cell lineage of neuronal subtypes in the mammalian cerebral cortex. 872 86

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

In this report, we have examined the requirement for the retinoblastoma (Rb) gene family in neuronal determination with a focus on the developing neocortex. To determine whether pRb is required for neuronal determination in vivo, we crossed the Rb-/- mice with transgenic mice expressing beta-galactosidase from the early, panneuronal Talpha1 alpha-tubulin promoter (Talpha1:nlacZ). In E12.5 Rb-/- embryos, the Talpha1:nlacZ transgene was robustly expressed throughout the developing nervous system. However, by E14. 5, there were perturbations in Talpha1:nlacZ expression throughout the nervous system, including deficits in the forebrain and retina. To more precisely define the temporal requirement for pRb in neuronal determination, we functionally ablated the pRb family in wild-type cortical progenitor cells that undergo the transition to postmitotic neurons in vitro by expression of a mutant adenovirus E1A protein. These studies revealed that induction of Talpha1:nlacZ did not require proteins of the pRb family. However, in their absence, determined, Talpha1:nlacZ-positive cortical neurons underwent apoptosis, presumably as a consequence of "mixed signals" deriving from their inability to undergo terminal mitosis. In contrast, when the pRb family was ablated in postmitotic cortical neurons, there was no effect on neuronal survival, nor did it cause the postmitotic neurons to reenter the cell cycle. Together, these studies define a critical temporal window of requirement for the pRb family; these proteins are not required for induction of neuronal gene expression or for the maintenance of postmitotic neurons, but are essential for determined neurons to exit the cell cycle and survive.
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PMID:A critical temporal requirement for the retinoblastoma protein family during neuronal determination. 950 81

The mouse keratocan gene (Ktcn) expression tracks the corneal morphogenesis during eye development and becomes restricted to keratocytes of the adult, implicating a cornea-specific gene regulation of the mouse Ktcn [J. Biol. Chem., 273 (1998) 22584-22588]. To examine the functionality of the mouse Ktcn promoter, we have cloned and sequenced a 3.2kb genomic DNA fragment 5' of the mouse Ktcn gene, which was used to prepare a reporter gene construct that contained the 3.2kb 5' flanking sequence, exon 1 and 0.4kb of intron 1 of Ktcn, and beta-geo hybrid reporter gene. The beta-galactosidase (betaGal) activity was assayed in tissues of two of five transgenic mouse lines obtained via microinjection. In adult transgenic mice, betaGal activity was detected only in cornea, not in other tissues (e.g. lens, retina, sclera, lung, heart, liver, diaphragm, kidney, and brain). During ocular development, the spatial-temporal expression patterns of the betaGal recapitulated that of endogenous Ktcn in transgenic mice. Using XGal staining, strong betaGal activity was first detected in periocular tissues of E13.5 embryos, and restricted to corneal keratocytes at E14.5 and thereafter. Interestingly, in addition to cornea, betaGal activity was transiently found in some non-ocular tissues, i.e. ears, snout, and limbs of embryos of E13.5 and E14.5 but was no longer detected in those tissues of E16.5 embryos. The transient expression of endogenous keratocan in non-ocular tissues during embryonic development was confirmed by in situ hybridization. Taken together, our results suggest that the 3.2kb Ktcn promoter contains sufficient cis-regulatory elements to drive heterologous minigene expression in cells expressing keratocan. The identification of keratocyte-specific expression of betaGal reporter gene in the adult transgenic mice is an important first step in characterizing the Ktcn promoter in order to use it to drive a foreign gene expression in corneal stroma.
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PMID:Identification of a 3.2 kb 5'-flanking region of the murine keratocan gene that directs beta-galactosidase expression in the adult corneal stroma of transgenic mice. 1085 82

Vascular endothelial growth factor (VEGF) is required for endothelial cell differentiation, vasculogenesis, and normal glomerular vascularization. To examine whether VEGF plays a role as a chemoattractant for the developing kidney vasculature, avascular metanephric kidneys from rat embryos (E14) were cocultured with endothelial cells. To determine whether VEGF directly provides chemoattractive guidance for migration, we examined migration of endothelial cells toward VEGF-coated beads. Mouse glomerular endothelial cells expressing beta-galactosidase (MGEC) were isolated from Flk-1(+/-) heterozygous mice and passaged 4-12 times. Upon 24 h culture on collagen I gels MGEC formed a lattice or capillary-like network. Embryonic metanephroi were cocultured with MGEC on collagen I gels for 1-6 days in defined media, stained for beta-galactosidase, and examined by light microscopy. Metanephric organs induced a rearrangement of the endothelial cell lattice and attracted MGEC. MGEC invaded the metanephric organs forming capillary-like structures within and surrounding the forming nephrons. This process was accelerated and amplified by low oxygen (3% O(2)) and was prevented by anti-VEGF neutralizing antibodies. MGECs migrated toward VEGF-coated beads, whereas PBS-coated beads did not alter MGEC networks. We conclude that VEGF produced by the differentiating nephrons acts as a chemoattractant providing spatial direction to developing capillaries toward forming nephrons during metanephric development in vitro.
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PMID:VEGF spatially directs angiogenesis during metanephric development in vitro. 1107 74

Gene trapping in mouse embryonic stem cells is an efficient method for identifying new genes and examining their functions. This method has been used in an effort to identify some novel genes involved in mouse development. In the present paper, one such gene named IZP6 is reported. Expression of the IZP6 gene, as monitored by beta-galactosidase expression in heterozygous mice, was detected in a developmentally regulated fashion: the expression pattern has two phases during the embryogenesis. In the first phase, from embryonic day 11.5 (E11.5) until E14.5, the reporter gene is mainly expressed in the forebrain. In the second phase, from E15.5 until birth, expression in the forebrain becomes weaker but is still observed in the olfactory bulb and the skin around the eyes, nose, limbs and tail. Thus, IZP6 gene expression changes from the central nervous system (the first phase) to the peripheral tissues (the second phase) during development. The IZP6 gene encodes a protein of 228 amino acids. Analysis of the secondary structure of the IZP6 protein revealed four hydrophobic regions, indicating that the IZP6 protein is a four transmembrane region protein. These results suggest that IZP6 is a transmembrane protein related to neurogenesis in the mouse.
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PMID:A novel putative transmembrane protein, IZP6, is expressed in neural cells during embryogenesis. 1142 94

In the pancreas, ligands of receptor tyrosine kinases (RTKs) are thought to be implicated in the development and function of the islets of Langerhans, which represent the endocrine part of the pancreas. In a previous study, we randomly screened by reverse transcriptase-polymerase chain reaction for RTKs expressed in the embryonic pancreas. One cDNA fragment that was cloned during this screen corresponded to the KIT receptor. The objective of the present study was to analyze the pattern of Kit expression in the pancreas. We demonstrated that Kit is expressed and functional in terms of signal transduction in the insulin-producing cell line INS-1. Indeed, upon treatment with the KIT ligand (KITL), the extracellular signal-regulated protein kinase was phosphorylated, and the expression of early responsive genes was induced. We also demonstrated that Kit mRNAs are present in fetal and adult rat islets. We next used mice that had integrated the lacZ reporter gene into the Kit locus. In these mice, beta-galactosidase (beta-gal) served as a convenient marker for expression of the endogenous Kit gene. Kit was found to be specifically transcribed in beta-cells (insulin-expressing cells), whereas no expression was found in other endocrine cell types or in the exocrine tissue. Interestingly, not all mature beta-cells expressed Kit, indicating that Kit is a marker of a subpopulation of beta-cells. Finally, by following beta-gal expression in the pancreas during fetal life, we found that at E14.5, Kit is expressed in both insulin- and glucagon-expressing cells present at that stage, and also in a specific cell population present in the epithelium that stained negative for endocrine markers. These data suggest that these Kit-positive/endocrine-negative cells could represent a subpopulation of endocrine cell precursors.
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PMID:Expression of the receptor tyrosine kinase KIT in mature beta-cells and in the pancreas in development. 1152 67

The human RUNX3/AML2 gene belongs to the 'runt domain' family of transcription factors that act as gene expression regulators in major developmental pathways. Here, we describe the expression pattern of Runx3 during mouse embryogenesis compared to the expression pattern of Runx1. E10.5 and E14.5-E16.5 embryos were analyzed using both immunohistochemistry and beta-galactosidase activity of targeted Runx3 and Runx1 loci. We found that Runx3 expression overlapped with that of Runx1 in the hematopoietic system, whereas in sensory ganglia, epidermal appendages, and developing skeletal elements, their expression was confined to different compartments. These data provide new insights into the function of Runx3 and Runx1 in organogenesis and support the possibility that cross-regulation between them plays a role in embryogenesis.
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PMID:Spatial and temporal expression pattern of Runx3 (Aml2) and Runx1 (Aml1) indicates non-redundant functions during mouse embryogenesis. 1173 Dec 60


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