Hedgehog is required for activation of engrailed during regeneration of fragmented Drosophila imaginal discs

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1591-1599 ◽  
Author(s):  
M.C. Gibson ◽  
G. Schubiger

Surgically fragmented Drosophila appendage primordia (imaginal discs) engage in wound healing and pattern regulation during short periods of in vivo culture. Prothoracic leg disc fragments possess exceptional regulative capacity, highlighted by the ability of anterior cells to convert to posterior identity and establish a novel posterior compartment. This anterior/posterior conversion violates developmental lineage restrictions essential for normal growth and patterning of the disc, and thus provides an ideal model for understanding how cells change fate during epimorphic pattern regulation. Here we present evidence that the secreted signal encoded by hedgehog directs anterior/posterior conversion by activating the posterior-specific transcription factor engrailed in regulating anterior cells. In the absence of hedgehog activity, prothoracic leg disc fragments fail to undergo anterior/posterior conversion, but can still regenerate missing anterior pattern elements. We suggest that hedgehog-independent regeneration within the anterior compartment (termed integration) is mediated by the positional cues encoded by wingless and decapentaplegic. Taken together, our results provide a novel mechanistic interpretation of imaginal disc pattern regulation and permit speculation that similar mechanisms could govern appendage regeneration in other organisms.

Development ◽  
1998 ◽  
Vol 125 (15) ◽  
pp. 2771-2780 ◽  
Author(s):  
F. Maschat ◽  
N. Serrano ◽  
N.B. Randsholt ◽  
G. Geraud

Engrailed is a nuclear regulatory protein with essential roles in embryonic segmentation and wing morphogenesis. One of its regulatory targets in embryos was shown to be the Polycomb group gene, polyhomeotic. We show here that transheterozygous adult flies, mutant for both engrailed and polyhomeotic, show a gap in the fourth vein. In the corresponding larval imaginal discs, a polyhomeotic-lacZ enhancer trap is not normally activated in anterior cells adjacent to the anterior-posterior boundary. This intermediary region corresponds to the domain of low engrailed expression that appears in the anterior compartment, during L3. Several arguments show that engrailed is responsible for the induction of polyhomeotic in these cells. The role of polyhomeotic in this intermediary region is apparently to maintain the repression of hedgehog in the anterior cells abutting the anterior-posterior boundary, since these cells ectopically express hedgehog when polyhomeotic is not activated. This leads to ectopic expressions first of patched, then of cubitus interruptus and decapentaplegic in the posterior compartment, except for the dorsoventral border cells that are not affected. Thus posterior cells express a new set of genes that are normally characteristic of anterior cells, suggesting a change in the cell identity. Altogether, our data indicate that engrailed and polyhomeotic interactions are required to maintain the anterior-posterior boundary and the posterior cell fate, just prior to the evagination of the wing.


Development ◽  
1997 ◽  
Vol 124 (1) ◽  
pp. 79-89 ◽  
Author(s):  
M.A. Singer ◽  
A. Penton ◽  
V. Twombly ◽  
F.M. Hoffmann ◽  
W.M. Gelbart

The imaginal disk expression of the TGF-beta superfamily member DPP in a narrow stripe of cells along the anterior-posterior compartment boundary is essential for proper growth and patterning of the Drosophila appendages. We examine DPP receptor function to understand how this localized DPP expression produces its global effects upon appendage development. Clones of saxophone (sax) or thick veins (tkv) mutant cells, defective in one of the two type I receptors for DPP, show shifts in cell fate along the anterior-posterior axis. In the adult wing, clones that are homozygous for a null allele of sax or a hypomorphic allele of tkv show shifts to more anterior fates when the clone is in the anterior compartment and to more posterior fates when the clone is in the posterior compartment. The effect of these clones upon the expression pattern of the downstream gene spalt-major also correlates with these specific shifts in cell fate. The similar effects of sax null and tkv hypomorphic clones indicate that the primary difference in the function of these two receptors during wing patterning is that TKV transmits more of the DPP signal than does SAX. Our results are consistent with a model in which a gradient of DPP reaches all cells in the developing wing blade to direct anterior-posterior pattern.


Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3359-3369 ◽  
Author(s):  
T. Tabata ◽  
C. Schwartz ◽  
E. Gustavson ◽  
Z. Ali ◽  
T.B. Kornberg

Anterior/posterior compartment borders bisect every Drosophila imaginal disc, and the engrailed gene is essential for their function. We analyzed the role of the engrailed and invected genes in wing discs by eliminating or increasing their activity. Removing engrailed/invected from posterior wing cells created two new compartments: an anterior compartment consisting of mutant cells and a posterior compartment that grew from neighboring cells. In some cases, these compartments formed a complete new wing. Increasing engrailed activity also affected patterning. These findings demonstrate that engrailed both directs the posterior compartment pathway and creates the compartment border. These findings also establish the compartment border as the pre-eminent organizational feature of disc growth and patterning.


Development ◽  
1989 ◽  
Vol 107 (4) ◽  
pp. 715-722 ◽  
Author(s):  
A.A. Simcox ◽  
I.J.H. Roberts ◽  
E. Hersperger ◽  
M.C. Gribbin ◽  
A. Shearn ◽  
...  

Drosophila embryos homozygous for strong mutations in each of the segment-polarity genes wingless (wg), engrailed (en), naked (nkd) and patched (ptc) form a larval cuticle in which there is a deletion in every segment. The mutant embryos normally fail to hatch but by in vivo culture we were able to show which could produce adult structures. Cultured wg- embryos did not produce any adult structures. Cultured en- embryos produced eye-antennal derivatives and rarely produced partial thoracic structures. nkd- and ptc- embryos produced eye-antennal and thoracic derivatives. The nkd- and ptc- thoracic imaginal discs developed with an abnormal morphology and abnormal pattern of en- expression. Our findings are consistent with the idea that the thoracic imaginal discs derive from two adjacent groups of cells that express wg and en respectively in the embryo.


1984 ◽  
Vol 62 (2) ◽  
pp. 157-160
Author(s):  
P. Sivasubramanian

Two stages of postfeeding, third-instar larvae of Sarcophaga bullata were injected with 5-bromodeoxyuridine to examine the effect of the analogue on pupariation and adult differentiation. While pupariation was inhibited in prered spiracle-stage larvae, adult differentiation was unaffected in both stages as revealed by in vivo culture of imaginal discs. It is suggested BudR may be more effective in disturbing certain biochemical processes than in inhibiting morphogenesis.


Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 4943-4948 ◽  
Author(s):  
Y. Chen ◽  
G. Struhl

During Drosophila development, cells belonging to the posterior compartment of each segment organize growth and patterning by secreting Hedgehog (Hh), a protein which induces a thin strip of adjacent cells in the anterior compartment to express the morphogens Decapentaplegic (Dpp) and Wingless (Wg). Hedgehog is bound and transduced by a receptor complex that includes Smoothened (Smo), a member of the Frizzled (Fz) family of seven-pass transmembrane receptors, as well as the multiple-pass transmembrane protein Patched (Ptc). Ptc is required for the binding of Hh to the complex as well as for the Hh-dependent activation of Smo within the complex. Here, we identify a likely null allele of the smo gene and use it to determine whether Hh is bound by Ptc alone, or by Smo in concert with Ptc. We find that cells devoid of Smo can sequester Hh, but that their ability to do so depends, as in wild-type cells, on the expression of high levels of Ptc protein. These results suggest that Ptc normally binds Hh without any help from Smo and hence favor a mechanism of signal transduction in which Hh binds specifically to Ptc and induces a conformational change leading to the release of latent Smo activity.


Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3467-3476 ◽  
Author(s):  
J.F. de Celis ◽  
M. Ruiz-Gomez

Drosophila imaginal discs are divided into units called compartments. Cells belonging to the same compartment are related by lineage and express a characteristic set of ‘selector genes’. The borders between compartments act as organizing centres that influence cell growth within compartments. Thus, in the cells immediately anterior to the anterior-posterior compartment boundary the presence of the hedgehog product causes expression of decapentaplegic, which, in turn, influences the growth and patterning of the wing disc. The normal growth of the disc requires that posterior-specific genes, such as hedgehog and engrailed are not expressed in cells of the anterior compartment. Here we show that hedgehog can activate engrailed in the anterior compartment and that both hedgehog and engrailed are specifically repressed in anterior cells by the activity of the neurogenic gene groucho. In groucho mutant discs, hedgehog and engrailed are expressed at the dorsoventral boundary of the anterior compartment, leading to the ectopic activation of decapentaplegic and patched and to a localised increase in cell growth associated with pattern duplications. The presence of engrailed in the anterior compartment causes the transformation of anterior into posterior structures.


Development ◽  
1995 ◽  
Vol 121 (6) ◽  
pp. 1625-1635 ◽  
Author(s):  
C. Schwartz ◽  
J. Locke ◽  
C. Nishida ◽  
T.B. Kornberg

The cubitus interruptus (ci) gene of Drosophila is expressed in all anterior compartment cells in both embryos and imaginal disks where it encodes a putative zinc-finger protein related to the vertebrate Gli and C. elegans Tra-1 proteins. Using ci/lacZ fusions, we located regulatory sequences responsible for the normal pattern of ci expression, and obtained evidence that separate elements regulate its expression in embryos and imaginal disks. Mutants that delete a portion of this regulatory region express ci ectopically in the posterior compartments of their wing imaginal disks and have wings with malformed posterior compartments. Similar deletions of ci/lacZ fusion constructs also result in ectopic posterior compartment expression. Evidence that the engrailed protein normally represses ci in posterior compartments includes the expansion of ci expression into posterior compartment cells that lack engrailed function, diminution of ci expression upon overexpression of engrailed protein in anterior compartment cells, and the ability of engrailed protein to bind to the ci regulatory region in vivo and in vitro. We suggest that engrailed protein directly represses ci expression in posterior compartment cells.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eren Akbaba ◽  
Burak Sezgin

Abstract Background Laparoscopic lateral suspension (LLS) is a laparoscopic technique used to treat pelvic organ prolapse (POP) in apical and anterior compartment defect with the use of a synthetic T-shaped mesh graft. The posterior compartment is repaired using a second mesh or a procedure along with LLS, such as posterior colporrhaphy. The aim of this study was to evaluate the clinical results of LLS for POP using a five-arm mesh instead of a T-shaped mesh graft to repair the defect of the posterior compartment in addition to the apical and anterior compartments. Methods Data from 37 patients with a diagnosis of advanced-stage (≥ 3) POP undergoing LLS with the use of a five-arm mesh were retrospectively analysed. Pre-operative and post-operative examinations and, surgical outcomes were determined. The results of measurements and examinations, reoperation rates, erosion rates, lower urinary tract symptoms, and complications were analysed. The Prolapse Quality of Life Questionnaire (P-QOL) was also used. Results The median post-operative follow-up was 20 (13–34) months. There was a significant improvement in POP-Q scores in all treated compartments, with overall objective cure rates of 94.5% for the apical compartment, 86.4% for the anterior compartment, and 91.8% for the posterior compartment. The median operative time was 96 (76–112) minutes. The median length of hospitalization was 2 (1–3) days. A significant improvement in vaginal bulge, urinary urgency, incomplete voiding, urinary frequency, and constipation was observed after surgery. The sexuality among patients increased from 13 (35.1%) preoperatively to 22 (59.4%) post-operatively. De novo stress urinary incontinence developed in 7 (18.9%) patients. The P-QOL scores improved significantly after surgery. Conclusions In advanced-stage POP patients, the posterior compartment damage can also be repaired in LLS with the use of a single five-arm mesh without the need for an additional procedure, and the recurrence rate can be reduced.


Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 139-149 ◽  
Author(s):  
S.L. Ang ◽  
J. Rossant

We have developed germ layer explant culture assays to study the role of mesoderm in anterior-posterior (A-P) patterning of the mouse neural plate. Using isolated explants of ectodermal tissue alone, we have demonstrated that the expression of Engrailed-1 (En-1) and En-2 genes in ectoderm is independent of mesoderm by the mid- to late streak stage, at least 12 hours before their onset of expression in the neural tube in vivo at the early somite stage. In recombination explants, anterior mesendoderm from headfold stage embryos induces the expression of En-1 and En-2 in pre- to early streak ectoderm and in posterior ectoderm from headfold stage embryos. In contrast, posterior mesendoderm from embryos of the same stage does not induce En genes in pre- to early streak ectoderm but is able to induce expression of a general neural marker, neurofilament 160 × 10(3) M(r). These results provide the first direct evidence for a role of mesendoderm in induction and regionalization of neural tissue in mouse.


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