wingless
Wingless autoregulation - role of Gooseberry and Lady bird Gooseberry is required for Hedgehog independent wg autoregulation. Direct wg autoregulation (autocrine signaling) is masked by its paracrine role in maintaining hh, which in turn maintains wg. zeste-white3 (zw3) and ptc mutant backgrounds have been used to uncouple genetically this positive-feedback loop and to study autocrine wg signaling. Direct wg autoregulation differs from WG signalling to adjacent cells in the importance of fused, smoothened and cubitus interruptus relative to zw3 and armadillo. wg autoregulation during this early hh-dependent phase differs from later wg autoregulation by lack of gooseberry participation (Hooper, 1994).
The main function of gsb is the maintenance of wg expression by a wg-gsb autoregulatory loop after 6 h of development. The repression of denticles by the wg signal is different from the wg signaling pathways that activate gsb or en. Mutual activations involving gsb, wg and en show temporal asymmetries which lead to their different mutant phenotypes (Li, 1993b).
porcupine is required for wingless autoregulation. There are two pathways through which wg regulates its own transcription. One pathway involves porcupine and is required for direct wg autoregulation. The second involves engrailed in adjacent cells resulting in a paracrine feedback loop involving dsh, shaggy/zw3 and arm and is also required for the specification of naked cuticle and the generation of cell diversity (Manoukian, 1995).
In addition to their role in the specification of the epidermal pattern in each segment, several segment polarity genes, including gooseberry (gsb), specify cell fate in the Drosophila central nervous system (CNS). Analyses of the gsb CNS phenotype have been complicated by the fact that the previously available gsb mutants, all caused by cytologically visible deficiencies, have severe segmentation defects and also lack a number of additional genes. Two novel gsb mutants have been characterized that have CNS defects, due to their hypomorphic nature, but have only weak or no segmentation defects. These gsb alleles, as well as gsb rescue experiments, have allowed a determination of which aspects of the deficiency mutant phenotypes can be attributed to loss of gsb. gsb mutants lack U and CQ neurons, have duplicated RP2 neurons, and display posterior commissure defects. gsb neural defects, as well as the gsb cuticle defect, are differentially sensitive to the level of functional Gsb. One of the novel gsb alleles has been used in order to understand the genetic interactions between gsb, wingless, and patched during the patterning of the ventral neuroectoderm. In contrast to epidermal patterning, where Gsb is required to maintain wg transcription, Gsb antagonizes the Wg signal that confers neuroblast (NB) 4-2 fate. The antagonism of the Wg signal by Gsb may be a common theme to many signal transduction and cell patterning systems. A secreted signaling molecule confers a particular cell fate on adjacent cells; at the same time, the signaling molecule regulates expression of a transcription factor within the cells which secrete the signal, effectively preventing these cells from taking on the fate conferred by the signal (Duman-Scheel, 1997).
Expression of lady bird early and lady bird late depends on wingless. Previous studies have shown that ubiquitous expression of gooseberry ectopically activates the endogenous gsb gene in cells located anterior to the wild-type stripe. However, this ectopic induction is not observed in a wingless mutant background (Li, 1993b). Heat shock gsb is also able to activate the formation of an ectopic strip of lbe. As for gsb, this phenomenon is wg-dependent and cannot be detected in wg mutants. Therefore, it is likely that wg function is required for both activation and maintenance of lbe and lbl expression, and for that matter, gsb as well (Jagla, 1997). In the dorsal epidermis, both wg and lbe are gsb-independent. It is concluded that whereas ventral epidermal wg expression may require gsb, in the dorsal epidermis, both wg and lbe are gsb-independent (Jagla, 1997).
The Drosophila ventral nerve cord derives from neural progenitor cells called neuroblasts. Individual neuroblasts have unique gene expression profiles and give rise to distinct clones of neurons and glia. The specification of neuroblast identity provides a cell intrinsic mechanism which ultimately results in the generation of progeny which are different from one another. Segment polarity genes have a dual function in early neurogenesis: within distinct regions of the neuroectoderm, they are required both for neuroblast formation and for the specification of neuroblast identity. Previous studies of segment polarity gene function largely focused on neuroblasts that arise within the posterior part of the segment. This study shows that the segment polarity gene midline is required for neuroblast formation in the anterior-most part of the segment. Moreover, midline contributes to the specification of anterior neuroblast identity by negatively regulating the expression of Wingless and positively regulating the expression of Mirror. In the posterior-most part of the segment, midline and its paralog, H15, have partially redundant functions in the regulation of the NB marker Eagle. Hence, the segment polarity genes midline and H15 play an important role in the development of the ventral nerve cord in the anterior- and posterior-most part of the segment (Buescher, 2006).
Individual NB identity is specified in the NE by the overlapping expression of segment polarity and dorso-ventral patterning genes; loss of segment polarity gene function results in misspecification of NBs along the antero-posterior axis. mid functions in the NE to break the symmetry of Hh-signaling and loss of mid results in ectopic neuroectodermal Wg expression posterior to the En/Hh domain. In wt embryos, Wg-positive NE gives rise to the row 5 NBs, all of which are Wg-positive at the time of birth. To examine whether the ectopic neuroectodermal expression of Wg results in ectopic Wg expression in NBs, stage 11 mid mutant embryos were stained with the anti-Wg antibody. Wg-positive NBs were observed in row 1/2 predominantly in odd-numbered segments. Ectopic Wg in NBs was only partially penetrant and highly variable with respect to the DV position (identity) of the affected NBs, most probably reflecting the substantial loss of NBs in this region. Removal of both copies of mid and H15 did not enhance the severity of the phenotype. These data show that mid, but not H15, is required to prevent the formation of Wg expressing NBs in row 1/2 in odd-numbered abdominal segments (Buescher, 2006).
Wingless interactions with dpp Overexpression of decapentaplegic reveals a reciprocal interaction between wg and dpp in wing and leg patterning. High levels of dpp lead to reduction of the scutellum, loss of one or more scutellar bristles, and duplication of posterior wing structures. In leg discs, intermediate increases in dpp cause the loss of ventral leg structures with the concomitant fusion of left and right dorsal forelegs. Supernumerary leg bifurcations are evident, and they arise exclusively from the anterior-ventral region of the leg (Jiang, 1996).
Decapentaplegic is expressed at the disc's posterior margin prior to initiation. Under the control of hh, it is expressed in the furrow, during MF progression. While dpp has been implicated in eye disc growth and morphogenesis, its precise role in retinal differentiation has not been determined. To address the role of dpp in initiation and progression of retinal differentiation, the consequences of reduced and increased dpp function have been analyzed during eye development. dpp is not only required for normal MF initiation, but is sufficient to induce ectopic initiation of differentiation. Inappropriate initiation is normally inhibited by wingless. Loss of dpp function is accompanied by expansion of wg expression, while increased dpp function leads to loss of wg transcription. In addition, dpp is required to maintain, and sufficient to induce, its own expression along the disc's margins. It is thought that dpp autoregulation and dpp-mediated inhibition of wg expression are required for the coordinated regulation of furrow initiation and progression. In the later stages of retinal differentiation, reduction of dpp function leads to an arrest in MF progression (Chanut, 1997).
The finding that Wingless and Decapentaplegic suppress each others transcription provides a mechanism for creating developmental territories in fields of cells. What is the mechanism for that antagonism? The dishevelled and shaggy genes encode intracellular proteins generally thought of as downstream of WG signaling. The effects of changing either DSH or SGG activity were investigated on both cell fate and wg and dpp expression. At the level of cell fate in discs, DSH antagonizes SGG activity. At the level of gene expression, SGG positively regulates dpp expression and negatively regulates wg expression while DSH activity suppresses dpp expression and promotes wg expression. Sharp borders of gene expression correlating precisely with clone boundaries suggest that the effects of DSH and SGG on transcription of wg and dpp are not mediated by secreted factors but rather act through intracellular effectors. The interactions described here suggest a model for the antagonism between WG and DPP that is mediated via SGG. The model incorporates autoactivation and lateral inhibition, which are properties required for the production of stable patterns. In the Dorsal part of the leg disc, DPP signalling predominates; DPP together with SGG inhibit wg expression and the consequencent lack of inhibition of SGG promotes further dpp expression. In the ventral part of the disc, WG signaling predominates and WG acts through DSH to inhibit SGG activity thus removing the activator of dpp (SGG) and promotes its own expression by removing the combinatorial inhibition of SGG and DPP. The regulatory interactions described exhibit extensive ability to organize new pattern in response to manipulation or injury (Heslip, 1997).
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