The ventral nervous system defective gene controls proneural gene expression at two distinct steps during neuroblast formation in Drosophila

Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1517-1524 ◽  
Author(s):  
J.B. Skeath ◽  
G.F. Panganiban ◽  
S.B. Carroll
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Cluster Formation ◽  
Regulatory Region ◽  
Regulatory Elements ◽  
Drosophila Embryo ◽  
Proneural Gene ◽  
Lacz Reporter ◽  
Proneural Genes ◽  
Proneural Cluster

Within the Drosophila embryo, the formation of many neuroblasts depends on the functions of the proneural genes of the achaete-scute complex (AS-C): achaete (ac), scute (sc) and lethal of scute (l'sc), and the gene ventral nervous system defective (vnd). Here, we show that vnd controls neuroblast formation, in part, through its regulation of the proneural genes of the AS-C. vnd is absolutely required to activate ac, sc and l'sc gene expression in proneural clusters in specific domains along the medial column of the earliest arising neuroblasts. Using ac-lacZ reporter constructs, we determined that vnd controls proneural gene expression at two distinct steps during neuroblast formation through separable regulatory regions. First, vnd is required to activate proneural cluster formation within the medial column of every other neuroblast row through regulatory elements located 3′ to ac; second, through a 5′ regulatory region, vnd functions to increase or maintain proneural gene expression in the cell within the proneural cluster that normally becomes the neuroblast. By following neuroblast segregation in vnd mutant embryos, we show that the neuroectoderm forms normally and that the defects in neuroblast formation are specific to particular proneural clusters.

Targeting gene expression to the head: the Drosophila orthodenticle gene is a direct target of the Bicoid morphogen

Development ◽  
1998 ◽  
Vol 125 (21) ◽  
pp. 4185-4193 ◽  
Author(s):  
Q. Gao ◽  
R. Finkelstein
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Regulatory Element ◽  
Regulatory Region ◽  
Repeated Sequence ◽  
Drosophila Embryo ◽  
Sequence Motif ◽  
Specific Expression ◽  
Gap Gene

The Bicoid (Bcd) morphogen establishes the head and thorax of the Drosophila embryo. Bcd activates the transcription of identified target genes in the thoracic segments, but its mechanism of action in the head remains poorly understood. It has been proposed that Bcd directly activates the cephalic gap genes, which are the first zygotic genes to be expressed in the head primordium. It has also been suggested that the affinity of Bcd-binding sites in the promoters of Bcd target genes determines the posterior extent of their expression (the Gene X model). However, both these hypotheses remain untested. Here, we show that a small regulatory region upstream of the cephalic gap gene orthodenticle (otd) is sufficient to recapitulate early otd expression in the head primordium. This region contains two control elements, each capable of driving otd-like expression. The first element has consensus Bcd target sites that bind Bcd in vitro and are necessary for head-specific expression. As predicted by the Gene X model, this element has a relatively low affinity for Bcd. Surprisingly, the second regulatory element has no Bcd sites. Instead, it contains a repeated sequence motif similar to a regulatory element found in the promoters of otd-related genes in vertebrates. Our study is the first demonstration that a cephalic gap gene is directly regulated by Bcd. However, it also shows that zygotic gene expression can be targeted to the head primordium without direct Bcd regulation.

A regulatory region from the mouse Hox-2.2 promoter directs gene expression into developing limbs

Development ◽  
1991 ◽  
Vol 112 (3) ◽  
pp. 807-811 ◽  
Author(s):  
K. Schughart ◽  
C.J. Bieberich ◽  
R. Eid ◽  
F.H. Ruddle
Keyword(s):  
Gene Expression ◽  
Transgenic Mouse ◽  
Reporter Gene ◽  
Developmental Stages ◽  
Regulatory Region ◽  
Homeobox Gene ◽  
Regulatory Elements ◽  
Body Region ◽  
Lacz Gene ◽  
Mouse Lines

To characterize cis-acting regulatory elements of the murine homeobox gene, Hox-2.2, transgenic mouse lines were generated that contained the LacZ reporter gene under the control of different fragments from the presumptive Hox-2.2 promoter. A promoter region of 3600 base pairs (bp) was identified, which reproducibly directed reporter gene expression into specific regions of developing mouse embryos. At 8.5 days postcoitum (p.c.) reporter gene activity was detected in posterior regions of the lateral mesoderm and, in subsequent developmental stages, expression of the LacZ gene was restricted to specific regions of the developing limb buds and the mesenchyme of the ventrolateral body region. This pattern of Hox-2.2-LacZ expression was found in all transgenic embryos that have been generated with the 3.6 kb promoter fragment (two founder embryos and embryos from five transgenic lines). In addition, embryos from two transgenic mouse lines expressed the reporter gene at low levels in the developing central nervous system (CNS). Our results are consistent with the idea that in addition to their presumptive role in CNS and vertebrae development, Hox-2.2 gene products are involved in controlling pattern formation in developing limbs.

Regulation of proneural gene expression and cell fate during neuroblast segregation in the Drosophila embryo

Development ◽  
1992 ◽  
Vol 114 (4) ◽  
pp. 939-946 ◽  
Author(s):  
J.B. Skeath ◽  
S.B. Carroll
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Single Cells ◽  
Regulatory Protein ◽  
Drosophila Embryo ◽  
Proneural Gene ◽  
Developmental Pathway ◽  
Neurogenic Genes ◽  
Temporal And Spatial ◽  
Epidermal Development

The Drosophila embryonic central nervous system develops from sets of progenitor neuroblasts which segregate from the neuroectoderm during early embryogenesis. Cells within this region can follow either the neural or epidermal developmental pathway, a decision guided by two opposing classes of genes. The proneural genes, including the members of the achaete-scute complex (AS-C), promote neurogenesis, while the neurogenic genes prevent neurogenesis and facilitate epidermal development. To understand the role that proneural gene expression and regulation play in the choice between neurogenesis and epidermogenesis, we examined the temporal and spatial expression pattern of the achaete (ac) regulatory protein in normal and neurogenic mutant embryos. The ac protein is first expressed in a repeating pattern of four ectodermal cell clusters per hemisegment. Even though 5–7 cells initially express ac in each cluster, only one, the neuroblast, continues to express ac. The repression of ac in the remaining cells of the cluster requires zygotic neurogenic gene function. In embryos lacking any one of five genes, the restriction of ac expression to single cells does not occur; instead, all cells of each cluster continue to express ac, enlarge, delaminate and become neuroblasts. It appears that one key function of the neurogenic genes is to silence proneural gene expression within the nonsegregating cells of the initial ectodermal clusters, thereby permitting epidermal development.

Targeted modification of promoters

2021 ◽  
pp. 247-278
Author(s):  
Andika Gunadi ◽  
◽  
Ning Zhang ◽  
John J. Finer ◽  
◽  
...  
Keyword(s):  
Gene Expression ◽  
Genome Editing ◽  
Promoter Region ◽  
Regulatory Region ◽  
Regulatory Elements ◽  
Upstream Regulatory Region ◽  
Precise Control ◽  
Coding Regions ◽  
Gene Coding ◽  
Altered Regulation

Although most genome editing efforts focus on modifications to gene coding regions, this chapter emphasizes genome editing of the upstream regulatory regions. Thoughtful editing of the promoter region will ultimately lead to improved plants, modified for more precise control of the intensity and specificity of native gene expression. In this chapter, we present an overview of the promoter or upstream regulatory region of a gene, and describe how this sequence is defined and studied. We then describe how the composition and arrangements of cis-regulatory elements within the promoter and the leading intron associated with the promoter region have been studied using classical transgenic approaches to reveal what regulatory components might be suitable for genome editing approaches. Finally, we offer some suggestions for pursuit of promoter editing and gene expression modulation, which will eventually lead to modified plants with an altered regulation of native gene expression.

Neurogenic expression of snail is controlled by separable CNS and PNS promoter elements

Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 199-207 ◽  
Author(s):  
Y.T. Ip ◽  
M. Levine ◽  
E. Bier
Keyword(s):  
Regulatory Region ◽  
Neural Element ◽  
Proneural Gene ◽  
Lacz Expression ◽  
Proneural Genes ◽  
Growing Body ◽  
Mesoderm Formation ◽  
Separate Control ◽  
Early Neurogenesis ◽  
Developing Nervous System

The Drosophila snail (sna) gene is first expressed in cells giving rise to mesoderm and is required for mesoderm formation. sna is subsequently expressed in the developing nervous system. sna expression during neurogenesis evolves from segmentally repeated neuroectodermal domains to a pan-neural pattern. We have identified a 2.8 kb regulatory region of the sna promoter that drives LacZ expression in a faithful neuronal pattern. Deletion analysis of this region indicates that the pan-neural element is composed of separable CNS and PNS components. This finding is unexpected since all known genes controlling early neurogenesis, including the proneural genes (i.e. da and AS-C), are expressed in both the CNS and PNS. We also show that expression of sna during neurogenesis is largely independent of the proneural genes da and AS-C. The separate control of CNS and PNS sna expression and independence of proneural gene regulation add to a growing body of evidence that current genetic models of neurogenesis are substantially incomplete.

asense is a Drosophila neural precursor gene and is capable of initiating sense organ formation

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 1-17 ◽  
Author(s):  
M. Brand ◽  
A.P. Jarman ◽  
L.Y. Jan ◽  
Y.N. Jan
Keyword(s):  
Ectopic Expression ◽  
Sense Organ ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Gene Products ◽  
Proneural Gene ◽  
Proneural Genes ◽  
Helix Loop Helix ◽  
Normal Gene ◽  
Proneural Cluster

Neural precursor cells in Drosophila arise from the ectoderm in the embryo and from imaginal disc epithelia in the larva. In both cases, this process requires daughterless and the proneural genes achaete, scute and lethal-of-scute of the achaete-scute complex. These genes encode basic helix-loop-helix proteins, which are nuclear transcription factors, as does the asense gene of the achaete-scute complex. Our studies suggest that asense is a neural precursor gene, rather than a proneural gene. Unlike the proneural achaete-scute gene products, the asense RNA and protein are found in the neural precursor during its formation, but not in the proneural cluster of cells that gives rise to the neural precursor cell. Also, asense expression persists longer during neural precursor development than the proneural gene products; it is still expressed after the first division of the neural precursor. Moreover, asense is likely to be downstream of the proneural genes, because (1) asense expression is affected in proneural and neurogenic mutant backgrounds, (2) ectopic expression of asense protein with an intact DNA-binding domain bypasses the requirement for achaete and scute in the formation of imaginal sense organs. We further note that asense ectopic expression is capable of initiating the sense organ fate in cells that do not normally require the action of asense. Our studies therefore serve as a cautionary note for the inference of normal gene function based on the gain-of-function phenotype after ectopic expression.

scholarly journals Molecular topography of an entire nervous system

2020 ◽  
Author(s):  
Seth R Taylor ◽  
Gabriel Santpere ◽  
Alexis Weinreb ◽  
Alec Barrett ◽  
Molly B. Reilly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Web Application ◽  
Gene Families ◽  
Regulatory Elements ◽  
Individual Neuron ◽  
Specific Gene ◽  
C Elegans ◽  
Underlying Mechanisms ◽  
And Function

SummaryNervous systems are constructed from a deep repertoire of neuron types but the underlying gene expression programs that specify individual neuron identities are poorly understood. To address this deficit, we have produced an expression profile of all 302 neurons of the C. elegans nervous system that matches the single cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families. For example, each neuron class expresses unique codes of ∼23 neuropeptide-encoding genes and ∼36 neuropeptide receptors thus pointing to an expansive “wireless” signaling network. To demonstrate the utility of this uniquely comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression across the nervous system and (2) reveal adhesion proteins with potential roles in synaptic specificity and process placement. These data are available at cengen.org and can be interrogated at the web application CengenApp. We expect that this neuron-specific directory of gene expression will spur investigations of underlying mechanisms that define anatomy, connectivity and function throughout the C. elegans nervous system.

scholarly journals Chromatin accessibility analysis uncovers regulatory element landscape in prostate cancer progression

2020 ◽  
Author(s):  
Joonas Uusi-Mäkelä ◽  
Ebrahim Afyounian ◽  
Francesco Tabaro ◽  
Tomi Häkkinen ◽  
Alessandro Lussana ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Progression ◽  
Regulatory Element ◽  
Regulatory Region ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Prostate Cancer Progression ◽  
Accessibility Analysis ◽  
A Genome

AbstractAberrant oncogene functions and structural variation alter the chromatin structure in cancer cells. While gene regulation by chromatin states has been studied extensively, chromatin accessibility and its relevance in aberrant gene expression during prostate cancer progression is not well understood. Here, we report a genome-wide chromatin accessibility analysis of clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration-resistant prostate cancer (CRPC) and integrative analysis with transcriptome, methylome, and proteome profiles of the same samples to uncover disease-relevant regulatory elements and their association to altered gene expression during prostate cancer progression. While promoter accessibility is consistent during disease initiation and progression, at distal sites chromatin accessibility is variable enabling transcription factors (TFs) binding patterns that are differently activated in different patients and disease stages. We identify consistent progression-related chromatin alterations during the progression to CRPC. By studying the TF binding patterns, we demonstrate the activation and suppression of androgen receptor-driven regulatory programs during PC progression and identify complementary TF regulatory modules characterized by e.g. MYC and glucocorticoid receptor. By correlation analysis we assign at least one putative regulatory region for 62% of genes and 85% of proteins differentially expressed during prostate cancer progression. Taken together, our analysis of the chromatin landscape in PC identifies putative regulatory elements for the majority of cancer-associated genes and characterizes their impact on the cancer phenotype.

Neurogenic genes control gene expression at the transcriptional level in early neurogenesis and in mesectoderm specification

Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 219-224 ◽  
Author(s):  
M.D. Martin-Bermudo ◽  
A. Carmena ◽  
F. Jimenez
Keyword(s):  
Posttranscriptional Regulation ◽  
Drosophila Embryo ◽  
Transcriptional Level ◽  
Proneural Gene ◽  
Proneural Genes ◽  
Protein Levels ◽  
Neurogenic Genes ◽  
The Central Nervous System ◽  
Early Neurogenesis ◽  
The Relationship

The development of the central nervous system in the Drosophila embryo is initiated by the acquisition of neural potential by clusters of ectodermal cells, promoted by the activity of proneural genes. Proneural gene function is antagonized by neurogenic genes, resulting in the realization of the neural potential in a single cell per cluster. To analyse the relationship between proneural and neurogenic genes, we have studied, in specific proneural clusters and neuroblasts of wild-type and neurogenic mutants embryos, the expression at the RNA and protein levels of lethal of scute, the most important known proneural gene in central neurogenesis. We find that the restriction of lethal of scute expression that accompanies the restriction of the neural potential to the delaminating neuroblast is regulated at the transcriptional level by neurogenic genes. These genes, however, do not control the size of proneural clusters. Moreover, available antibodies do not provide evidence for an hypothetical posttranscriptional regulation of proneural proteins by neurogenic genes. We also find that neurogenic genes are required for the specification of the mesectoderm. This has been shown for neuralized and Notch, and could also be the case for Delta and for the Enhancer of split gene complex. Neurogenic genes would control at the transcriptional level the repression of proneural genes and the activation of single-minded in the anlage of the mesectoderm.

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