Role of the teashirt gene in Drosophila midgut morphogenesis: secreted proteins mediate the action of homeotic genes

Development ◽  
1994 ◽  
Vol 120 (10) ◽  
pp. 2799-2809 ◽  
Author(s):  
L.D. Mathies ◽  
S. Kerridge ◽  
M.P. Scott
Keyword(s):  
Target Genes ◽  
Secreted Proteins ◽  
Homeotic Gene ◽  
Homeotic Genes ◽  
Gene Target ◽  
Downstream Target ◽  
Visceral Mesoderm ◽  
Transcription Regulators ◽  
Midgut Development ◽  
Anterior Midgut

Homeotic genes control the development of embryonic structure by coordinating the activities of downstream ‘target’ genes. The identities and functions of target genes must be understood in order to learn how homeotic genes control morphogenesis. Drosophila midgut development is regulated by homeotic genes expressed in the visceral mesoderm, where two of their target genes have been identified. Both encode secreted proteins. The Ultrabithorax (Ubx) homeotic gene activates transcription of the decapentaplegic (dpp) gene, which encodes a TGF beta class protein, while in adjacent mesoderm cells the abdominal-A (abd-A) homeotic gene activates transcription of the wingless (wg) gene, which encodes a Wnt class protein. The homeotic genes Antennapedia (Antp) and Sex combs reduced (Scr) act in more anterior midgut regions. Here we report the identification of another homeotic gene target in the midgut mesoderm, the teashirt (tsh) gene, which encodes a protein with zinc finger motifs. tsh is necessary for proper formation of anterior and central midgut structures. Antp activates tsh in anterior midgut mesoderm. In the central midgut mesoderm Ubx, abd-A, dpp, and wg are required for proper tsh expression. The control of tsh by Ubx and abd-A, and probably also by Antp, is mediated by secreted signaling molecules. By responding to signals as well as localized transcription regulators, the tsh transcription factor is produced in a spatial pattern distinct from any of the homeotic genes.

scholarly journals Regulation of a decapentaplegic midgut enhancer by homeotic proteins

Development ◽  
1994 ◽  
Vol 120 (12) ◽  
pp. 3605-3619 ◽  
Author(s):  
J.R. Manak ◽  
L.D. Mathies ◽  
M.P. Scott
Keyword(s):  
Target Genes ◽  
Ectopic Expression ◽  
Homeotic Genes ◽  
Lacz Gene ◽  
Cell Fates ◽  
Downstream Target ◽  
Visceral Mesoderm ◽  
Close Proximity ◽  
Correct Pattern

The clustered homeotic genes encode transcription factors that regulate pattern formation in all animals, conferring cell fates by coordinating the activities of downstream ‘target’ genes. In the Drosophila midgut, the Ultrabithorax (Ubx) protein activates and the abdominalA (abd-A) protein represses transcription of the decapentaplegic (dpp) gene, which encodes a secreted signalling protein of the TGF beta class. We have identified an 813 bp dpp enhancer which is capable of driving expression of a lacZ gene in a correct pattern in the embryonic midgut. The enhancer is activated ectopically in the visceral mesoderm by ubiquitous expression of Ubx or Antennapedia but not by Sex combs reduced protein. Ectopic expression of abd-A represses the enhancer. Deletion analysis reveals regions required for repression and activation. A 419 bp subfragment of the 813 bp fragment also drives reporter gene expression in an appropriate pattern, albeit more weakly. Evolutionary sequence conservation suggests other factors work with homeotic proteins to regulate dpp. A candidate cofactor, the extradenticle protein, binds to the dpp enhancer in close proximity to homeotic protein binding sites. Mutation of either this site or another conserved motif compromises enhancer function. A 45 bp fragment of DNA from within the enhancer correctly responds to both UBX and ABD-A in a largely tissue-specific manner, thus representing the smallest in vivo homeotic response element (HOMRE) identified to date.

Homeotic complex and teashirt genes co-operate to establish trunk segmental identities in Drosophila

Development ◽  
1994 ◽  
Vol 120 (8) ◽  
pp. 2287-2296 ◽  
Author(s):  
P. de Zulueta ◽  
E. Alexandre ◽  
B. Jacq ◽  
S. Kerridge
Keyword(s):  
Heat Shock ◽  
Target Genes ◽  
Homeotic Genes ◽  
Sex Combs Reduced ◽  
Downstream Target ◽  
Functional Aspects ◽  
Sex Combs ◽  
Head Segment ◽  
Posterior Trunk ◽  
Segmental Identity

Homeotic genes determine the identities of metameres in Drosophila. We have examined functional aspects of the homeotic gene teashirt by ectopically expressing its product under the control of a heat-shock promoter during embryogenesis. Our results confirm that the gene is critical for segmental identity of the larva. Under mild heat-shock conditions, the Teashirt protein induces an almost complete transformation of the labial to prothoracic segmental identity, when expressed before 8 hours of development. Positive autoregulation of the endogenous teashirt gene and the presence of Sex combs reduced protein in the labium explain this homeosis. Patterns in the maxillary and a more anterior head segment are partly replaced with trunk ones. Additional Teashirt protein has no effect on the identity of the trunk segments where the gene is normally expressed; teashirt function is overridden by some homeotic complex acting in the posterior trunk. Strong heat-shock regimes provoke novel defects: ectopic sense organs differentiate in posterior abdominal segments and trunk pattern elements differentiate in the ninth abdominal segment. Teashirt acts in a partially redundant way with certain homeotic complex proteins but co-operates with them for the establishment of specific segment types. We suggest that Teashirt and HOM-C proteins regulate common sets of downstream target genes.

Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos

Development ◽  
1990 ◽  
Vol 110 (4) ◽  
pp. 1031-1040 ◽  
Author(s):  
R. Reuter ◽  
G.E. Panganiban ◽  
F.M. Hoffmann ◽  
M.P. Scott
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Homeotic Genes ◽  
Visceral Mesoderm ◽  
Drosophila Embryogenesis ◽  
Growth Factor Genes ◽  
Growth Factor Beta ◽  
Drosophila Embryos

During Drosophila embryogenesis homeotic genes control the developmental diversification of body structures. The genes probably coordinate the expression of as yet unidentified target genes that carry out cell differentiation processes. At least four homeotic genes expressed in the visceral mesoderm are required for midgut morphogenesis. In addition, two growth factor homologs are expressed in specific regions of the visceral mesoderm surrounding the midgut epithelium. One of these, decapentaplegic (dpp), is a member of the transforming growth factor beta (TGF-beta) family; the other, wingless (wg), is a relative of the mammalian proto-oncogene int-1. Here we show that the spatially restricted expression of dpp in the visceral mesoderm is regulated by the homeotic genes Ubx and abd-A. Ubx is required for the expression of dpp while abd-A represses dpp. One consequence of dpp expression is the induction of labial (lab) in the underlying endoderm cells. In addition, abd-A function is required for the expression of wg in the visceral mesoderm posterior to the dpp-expressing cells. The two growth factor genes therefore are excellent candidates for target genes that are directly regulated by the homeotic genes.

scholarly journals Boundaries support specific long-distance interactions between enhancers and promoters in Drosophila Bithorax complex

2018 ◽  
Author(s):  
Nikolay Postika ◽  
Mario Metzler ◽  
Markus Affolter ◽  
Martin Müller ◽  
Paul Schedl ◽  
...  
Keyword(s):  
Target Genes ◽  
Model Systems ◽  
Homeotic Genes ◽  
Bithorax Complex ◽  
Long Distance ◽  
Gene Target ◽  
Regulatory Domains ◽  
Insulator Elements

AbstractDrosophila bithorax complex (BX-C) is one of the best model systems for studying the role of boundaries (insulators) in gene regulation. Expression of three homeotic genes, Ubx, abd-A, and Abd-B, is orchestrated by nine parasegment-specific regulatory domains. These domains are flanked by boundary elements, which function to block crosstalk between adjacent domains, ensuring that they can act autonomously. Paradoxically, seven of the BX-C regulatory domains are separated from their gene target by at least one boundary, and must “jump over” the intervening boundaries. To understand the jumping mechanism, the Mcp boundary was replaced with Fab-7 and Fab-8. Mcp is located between the iab-4 and iab-5 domains, and defines the border between the set of regulatory domains controlling abd-A and Abd-B. When Mcp is replaced by Fab-7 or Fab-8, they direct the iab-4 domain (which regulates abd-A) to inappropriately activate Abd-B in abdominal segment A4. For the Fab-8 replacement, ectopic induction was only observed when it was inserted in the same orientation as the endogenous Fab-8 boundary. A similar orientation dependence for bypass activity was observed when Fab-7 was replaced by Fab-8. Thus, boundaries perform two opposite functions in the context of BX-C – they block crosstalk between neighboring regulatory domains, but at the same time actively facilitate long distance communication between the regulatory domains and their respective target genes.Author SummaryDrosophila bithorax complex (BX-C) is one of a few examples demonstrating in vivo role of boundary/insulator elements in organization of independent chromatin domains. BX-C contains three HOX genes, whose parasegment-specific pattern is controlled by cis-regulatory domains flanked by boundary/insulator elements. Since the boundaries ensure autonomy of adjacent domains, the presence of these elements poses a paradox: how do the domains bypass the intervening boundaries and contact their proper regulatory targets? According to the textbook model, BX-C regulatory domains are able to bypass boundaries because they harbor special promoter targeting sequences. However, contrary to this model, we show here that the boundaries themselves play an active role in directing regulatory domains to their appropriate HOX gene promoter.

The Drosophila homeotic target gene centrosomin (cnn) encodes a novel centrosomal protein with leucine zippers and maps to a genomic region required for midgut morphogenesis

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3861-3876 ◽  
Author(s):  
J.G. Heuer ◽  
K. Li ◽  
T.C. Kaufman
Keyword(s):  
Leucine Zipper ◽  
Target Genes ◽  
Developmental Process ◽  
Coiled Coil ◽  
Regional Identity ◽  
Homeotic Genes ◽  
Structural Protein ◽  
Accumulation Pattern ◽  
Visceral Mesoderm

The products of the homeotic genes in Drosophila are transcription factors that are necessary to impose regional identity along the anterior-posterior axis of the developing embryo. However, the target genes under homeotic regulation that control this developmental process are largely unknown. We have utilized an immunopurification method to clone target genes of the Antennapedia protein (ANTP). We present here the characterization of centrosomin (cnn), one of the target genes isolated using this approach. The spatial and temporal expression of the cnn gene in the developing visceral mesoderm (VM) of the midgut and the central nervous system (CNS) of wild-type and homeotic mutant embryos is consistent with the idea that cnn is a homeotic target. In the VM, Antp and abdominal-A (abd-A) negatively regulate cnn, while Ultrabithorax (Ubx) shows positive regulation. In the CNS, cnn is regulated positively by Antp and negatively by Ubx and abd-A. Characterization of a cDNA encoding CNN predicts a novel structural protein with three leucine zipper motifs and several coiled-coil domains exhibiting limited homology to the rod portion of myosin. Immunocytochemical results demonstrate that the cnn encoded protein is localized to the centrosome and the accumulation pattern is coupled to the nuclear and centrosome duplication cycles of cleavage. In addition, evidence suggests that the expression of the cnn gene in the VM correlates with the morphogenetic function of Ubx in that tissue, i.e., the formation of the second midgut construction. The centrosomal localization of CNN and the involvement of microtubules in midgut morphogenesis suggest that this protein may participate in mitotic spindle assembly and the mechanics of morphogenesis through an interaction with microtubules, either directly or indirectly.

A role for the mesoderm in endodermal migration and morphogenesis in Drosophila

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1135-1145 ◽  
Author(s):  
R. Reuter ◽  
B. Grunewald ◽  
M. Leptin
Keyword(s):  
Cell Migration ◽  
Mesenchymal Cell ◽  
Drosophila Embryo ◽  
Germ Band ◽  
Visceral Mesoderm ◽  
Continuous Layer ◽  
Posterior Midgut ◽  
Endodermal Cells ◽  
Midgut Development ◽  
Anterior Midgut

The endodermal midgut arises from two primordia, the anterior midgut (AMG) primordium and the posterior midgut (PMG) primordium, which are separated by almost the entire length of the Drosophila embryo. To form the midgut, these two parts have to extend towards each other and to fuse laterally on both sides of the yolk. Shortly before and during that movement, AMG and PMG are arranged as mesenchymal cell masses, but later the midgut cells form an epithelium. We show that these two aspects of midgut development, migration of AMG and PMG and transition to an epithelium, depend on the mesoderm. The extension of the midgut primordia is achieved by cell migration along the visceral mesoderm which forms a continuous layer of cells within the germ band. In mutant embryos lacking the entire mesoderm or failing to differentiate the visceral mesoderm, AMG and PMG are formed but do not migrate properly. In addition, they fail to form an epithelium and instead either remain as compact cell masses anterior and posterior to the yolk (in twist and snail mutant embryos) or only occasionally wrap around the yolk before embryogenesis is completed (in tinman-deficient embryos). We conclude that the visceral mesoderm serves as a substratum for the migrating endodermal cells and that the contact between visceral mesoderm and endoderm is required for the latter to become an epithelium.

Regional repression of a Drosophila POU box gene in the endoderm involves inductive interactions between germ layers

Development ◽  
1993 ◽  
Vol 117 (4) ◽  
pp. 1199-1210 ◽  
Author(s):  
M. Affolter ◽  
U. Walldorf ◽  
U. Kloter ◽  
A.F. Schier ◽  
W.J. Gehring
Keyword(s):  
Homeotic Gene ◽  
Homeotic Genes ◽  
Germ Layers ◽  
Central Domain ◽  
Signalling Molecules ◽  
Spatial Regulation ◽  
Visceral Mesoderm ◽  
Induction Process ◽  
Genes Encoding ◽  
Repression Domain

An induction process occurring between the mesodermal and the endodermal germ layers has recently been described in the regulation of the Drosophila homeotic gene labial (lab). We report here that proper spatial regulation of the Drosophila POU box gene pdm-1 products also involves interaction between these two germ layers. pdm-1 transcripts are initially present in both the anterior and the posterior endodermal midgut primordia. Upon fusion of the two primordia, transcripts disappear from two regions in the endoderm, a central domain and an anterior domain. The anterior repression domain of pdm-1 is independent of the expression of known homeotic genes and genes encoding secreted signalling molecules in the visceral mesoderm, both for its positioning and its repression. Repression in the central domain requires both the homeotic gene Ultrabithorax (Ubx) and the decapentaplegic (dpp) gene, which encodes a secreted protein. Both of these genes are also required for lab induction. However, the analysis of pdm-1 expression in various mutant backgrounds indicates that the regulation of lab and pdm-1 across germ layers is controlled by different genetic cascades. Our study indicates that dpp is not the signal that dictates central pdm-1 repression across germ layers and suggests that in the same midgut region, different signalling pathways result in the differential activation or repression of potential transcription factors.

scholarly journals Genomic regions required for morphogenesis of the Drosophila embryonic midgut.

Genetics ◽  
1995 ◽  
Vol 141 (3) ◽  
pp. 1087-1100 ◽  
Author(s):  
D Bilder ◽  
M P Scott
Keyword(s):  
Regulatory Gene ◽  
Cell Communication ◽  
Gene Families ◽  
Genomic Region ◽  
Hormonal Control ◽  
Homeotic Genes ◽  
Spatial Regulation ◽  
Visceral Mesoderm ◽  
Genomic Regions ◽  
Midgut Development

Abstract The Drosophila midgut is an excellent system for studying the cell migration, cell-cell communication, and morphogenetic events that occur in organ formation. Genes representative of regulatory gene families common to all animals, including homeotic, TGF beta, and Wnt genes, play roles in midgut development. To find additional regulators of midgut morphogenesis, we screened a set of genomic deficiencies for midgut phenotypes. Fifteen genomic intervals necessary for proper midgut morphogenesis were identified, three contain genes already known to act in the midgut. Three other genomic regions are required for formation of the endoderm or visceral mesoderm components of the midgut. Nine regions are required for proper formation of the midgut constrictions. The E75 ecdysone-induced gene, which encodes a nuclear receptor superfamily member, is the relevant gene in one region and is essential for proper formation of midgut constrictions. E75 acts downstream of the previously known constriction regulators or in parallel. Temporal hormonal control may therefore work in conjunction with spatial regulation by the homeotic genes in midgut development. Another genomic region is required to activate transcription of the homeotic genes Antp and Scr specifically in visceral mesoderm. The genomic regions identified by this screen provide a map to novel midgut development regulators.

A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis

Development ◽  
1990 ◽  
Vol 110 (4) ◽  
pp. 1041-1050 ◽  
Author(s):  
G.E. Panganiban ◽  
R. Reuter ◽  
M.P. Scott ◽  
F.M. Hoffmann
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Homeotic Gene ◽  
Homeotic Genes ◽  
Germ Layers ◽  
Visceral Mesoderm ◽  
Endodermal Cells ◽  
Homeotic Gene Expression

The decapentaplegic (dpp) gene product, a member of the transforming growth factor-beta family, is required in Drosophila embryos for normal gastrulation and the establishment of dorsal-ventral polarity in the embryo. dpp is also expressed at specific positions in the visceral mesoderm along the developing midgut. We find that mutations that eliminate the visceral mesoderm expression of dpp lead to defects in midgut morphogenesis and alter the spatially localized expression of the homeotic genes Sex combs reduced (Scr), Ultrabithorax (Ubx), and Antennapedia (Antp) in the visceral mesoderm. The extracellular dpp protein migrates from the visceral mesoderm across the apposing endodermal cell layer in a region of the endoderm that expresses the homeotic gene labial (lab). Mesodermal expression of dpp is required for the expression of lab in these endodermal cells indicating that dpp mediates an inductive interaction between the two germ layers. We propose that extracellular dpp protein regulates gut morphogenesis, in part, by regulating homeotic gene expression in the visceral mesoderm and endoderm of the developing midgut.

scholarly journals Identification of homeotic target genes in Drosophila melanogaster including nervy, a proto-oncogene homologue.

Genetics ◽  
1995 ◽  
Vol 140 (2) ◽  
pp. 573-586 ◽  
Author(s):  
P G Feinstein ◽  
K Kornfeld ◽  
D S Hogness ◽  
R S Mann
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Target Genes ◽  
Early Stage ◽  
Gene Expression Pattern ◽  
Morphological Characteristics ◽  
Subtractive Hybridization ◽  
Homeotic Genes ◽  
Target Gene Expression ◽  
Downstream Target

Abstract In Drosophila, the specific morphological characteristics of each segment are determined by the homeotic genes that regulate the expression of downstream target genes. We used a subtractive hybridization procedure to isolate activated target genes of the homeotic gene Ultrabithorax (Ubx). In addition, we constructed a set of mutant genotypes that measures the regulatory contribution of individual homeotic genes to a complex target gene expression pattern. Using these mutants, we demonstrate that homeotic genes can regulate target gene expression at the start of gastrulation, suggesting a previously unknown role for the homeotic genes at this early stage. We also show that, in abdominal segments, the levels of expression for two target genes increase in response to high levels of Ubx, demonstrating that the normal down-regulation of Ubx in these segments is functional. Finally, the DNA sequence of cDNAs for one of these genes predicts a protein that is similar to a human proto-oncogene involved in acute myeloid leukemias. These results illustrate potentially general rules about the homeotic control of target gene expression and suggest that subtractive hybridization can be used to isolate interesting homeotic target genes.

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