Hedgehog is an indirect regulator of morphogenetic furrow progression in the Drosophila eye disc

Pattern formation in the eye imaginal disc of Drosophila occurs in a wave that moves from posterior to anterior. The anterior edge of this wave is marked by a contracted band of cells known as the morphogenetic furrow, behind which photoreceptors differentiate. The movement of the furrow is dependent upon the secretion of the signalling protein Hedgehog (Hh) by more posterior cells, and it has been suggested that Hh acts as an inductive signal to induce cells to enter a furrow fate and begin differentiation. To further define the role of Hh in this process, we have analysed clones of cells lacking the function of the smoothened (smo) gene, which is required for transduction of the Hh signal and allows the investigation of the autonomous requirement for hh signalling. These experiments demonstrate that the function of hh in furrow progression is indirect. Cells that cannot receive/transduce the Hh signal are still capable of entering a furrow fate and differentiating normally. However, hh is required to promote furrow progression and regulate its rate of movement across the disc, since the furrow is significantly delayed in smo clones.

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Role of decapentaplegic in initiation and progression of the morphogenetic furrow in the developing Drosophila retina

Development ◽

10.1242/dev.124.2.559 ◽

1997 ◽

Vol 124 (2) ◽

pp. 559-567 ◽

Cited By ~ 23

Author(s):

F. Chanut ◽

U. Heberlein

Keyword(s):

Posterior Margin ◽

Imaginal Disc ◽

Photoreceptor Cells ◽

Morphogenetic Furrow ◽

Retinal Differentiation ◽

Eye Disc ◽

Forward Edge ◽

Eye Imaginal Disc ◽

Precise Role

Morphogenesis in the Drosophila retina initiates at the posterior margin of the eye imaginal disc by an unknown mechanism. Upon initiation, a wave of differentiation, its forward edge marked by the morphogenetic furrow (MF), proceeds anteriorly across the disc. Progression of the MF is driven by hedgehog (hh), expressed by differentiating photoreceptor cells. The TGF-beta homolog encoded by decapentaplegic (dpp) is expressed at the disc's posterior margin prior to initiation and in the furrow, under the control of hh, 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 we analyzed the consequences of reduced and increased dpp function during eye development. We find that 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 (wg). 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. We postulate that dpp autoregulation and dpp-mediated inhibition of wg expression are required for the coordinated regulation of furrow initiation and progression. Finally, we show that in the later stages of retinal differentiation, reduction of dpp function leads to an arrest in MF progression.

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The EGF receptor and notch signaling pathways control the initiation of the morphogenetic furrow duringDrosophilaeye development

Development ◽

10.1242/dev.128.14.2689 ◽

2001 ◽

Vol 128 (14) ◽

pp. 2689-2697 ◽

Cited By ~ 4

Author(s):

Justin P. Kumar ◽

Kevin Moses

Keyword(s):

Pattern Formation ◽

Notch Signaling ◽

Imaginal Disc ◽

Egf Receptor ◽

Retinal Development ◽

Growth Factor Receptor ◽

Leading Edge ◽

Morphogenetic Furrow ◽

Epidermal Growth ◽

Eye Imaginal Disc

The onset of pattern formation in the developing Drosophila retina begins with the initiation of the morphogenetic furrow, the leading edge of a wave of retinal development that transforms a uniform epithelium, the eye imaginal disc into a near crystalline array of ommatidial elements. The initiation of this wave of morphogenesis is under the control of the secreted morphogens Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg). We show that the Epidermal Growth Factor Receptor and Notch signaling cascades are crucial components that are also required to initiate retinal development. We also show that the initiation of the morphogenetic furrow is the sum of two genetically separable processes: (1) the ‘birth’ of pattern formation at the posterior margin of the eye imaginal disc; and (2) the subsequent ‘reincarnation’ of retinal development across the epithelium.

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Role of the morphogenetic furrow in establishing polarity in the Drosophila eye

Development ◽

10.1242/dev.121.12.4085 ◽

1995 ◽

Vol 121 (12) ◽

pp. 4085-4094 ◽

Cited By ~ 12

Author(s):

F. Chanut ◽

U. Heberlein

Keyword(s):

Ectopic Expression ◽

Morphogenetic Furrow ◽

Eye Disc ◽

Drosophila Eye ◽

Retinal Epithelium ◽

Anteroposterior Polarity ◽

Crystalline Array

The Drosophila retina is a crystalline array of 800 ommatidia whose organization and assembly suggest polarization of the retinal epithelium along anteroposterior and dorsoventral axes. The retina develops by a stepwise process following the posterior-to-anterior progression of the morphogenetic furrow across the eye disc. Ectopic expression of hedgehog or local removal of patched function generates ectopic furrows that can progress in any direction across the disc leaving in their wake differentiating fields of ectopic ommatidia. We have studied the effect of these ectopic furrows on the polarity of ommatidial assembly and rotation. We find that the anteroposterior asymmetry of ommatidial assembly parallels the progression of ectopic furrows, regardless of their direction. In addition, ommatidia developing behind ectopic furrows rotate coordinately, forming equators in various regions of the disc. Interestingly, the expression of a marker normally restricted to the equator is induced in ectopic ommatidial fields. Ectopic equators are stable as they persist to adulthood, where they can coexist with the normal equator. Our results suggest that ectopic furrows can impart polarity to the disc epithelium, regarding the direction of both assembly and rotation of ommatidia. We propose that these processes are polarized as a consequence of furrow propagation, while more global determinants of dorsoventral and anteroposterior polarity may act less directly by determining the site of furrow initiation.

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The role of Wingless signaling in establishing the anteroposterior and dorsoventral axes of the eye disc

Development ◽

10.1242/dev.128.9.1519 ◽

2001 ◽

Vol 128 (9) ◽

pp. 1519-1529 ◽

Cited By ~ 3

Author(s):

J.D. Lee ◽

J.E. Treisman

Keyword(s):

Signaling Molecules ◽

Morphogenetic Furrow ◽

Wild Type ◽

Dorsoventral Axis ◽

Eye Disc ◽

Wingless Signaling ◽

Drosophila Eye ◽

Ectopic Activation ◽

Lateral Margins

The posteriorly expressed signaling molecules Hedgehog and Decapentaplegic drive photoreceptor differentiation in the Drosophila eye disc, while at the anterior lateral margins Wingless expression blocks ectopic differentiation. We show here that mutations in axin prevent photoreceptor differentiation and lead to tissue overgrowth and that both these effects are due to ectopic activation of the Wingless pathway. In addition, ectopic Wingless signaling causes posterior cells to take on an anterior identity, reorienting the direction of morphogenetic furrow progression in neighboring wild-type cells. We also show that signaling by Decapentaplegic and Hedgehog normally blocks the posterior expression of anterior markers such as Eyeless. Wingless signaling is not required to maintain anterior Eyeless expression and in combination with Decapentaplegic signaling can promote its downregulation, suggesting that additional molecules contribute to anterior identity. Along the dorsoventral axis of the eye disc, Wingless signaling is sufficient to promote dorsal expression of the Iroquois gene mirror, even in the absence of the upstream factor pannier. However, Wingless signaling does not lead to ventral mirror expression, implying the existence of ventral repressors.

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wingless inhibits morphogenetic furrow movement in the Drosophila eye disc

Development ◽

10.1242/dev.121.11.3519 ◽

1995 ◽

Vol 121 (11) ◽

pp. 3519-3527 ◽

Cited By ~ 44

Author(s):

J.E. Treisman ◽

G.M. Rubin

Keyword(s):

Posterior Margin ◽

Ectopic Expression ◽

Spatial Localization ◽

Morphogenetic Furrow ◽

Differentiated Cells ◽

Repetitive Process ◽

Eye Disc ◽

Drosophila Eye ◽

Lateral Margins ◽

Eye Imaginal Disc

Differentiation of the Drosophila eye imaginal disc is an asynchronous, repetitive process which proceeds across the disc from posterior to anterior. Its propagation correlates with the expression of decapentaplegic at the front of differentiation, in the morphogenetic furrow. Both differentiation and decapentaplegic expression are maintained by Hedgehog protein secreted by the differentiated cells posterior to the furrow. However, their initiation at the posterior margin occurs prior to hedgehog expression by an unknown mechanism. We show here that the wingless gene contributes to the correct spatial localization of initiation. Initiation of the morphogenetic furrow is restricted to the posterior margin by the presence of wingless at the lateral margins; removal of wingless allows lateral initiation. Ectopic expression of wingless at the posterior margin can also inhibit normal initiation. In addition, the presence of wingless in the center of the disc can prevent furrow progression. These effects of wingless are achieved without altering the expression of decapentaplegic.

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Hsc70 is required for endocytosis and clathrin function in Drosophila

The Journal of Cell Biology ◽

10.1083/jcb.200205086 ◽

2002 ◽

Vol 159 (3) ◽

pp. 477-487 ◽

Cited By ~ 79

Author(s):

Henry C. Chang ◽

Sherri L. Newmyer ◽

Michael J. Hull ◽

Melanie Ebersold ◽

Sandra L. Schmid ◽

...

Keyword(s):

Mutant Allele ◽

Imaginal Disc ◽

Substantial Reduction ◽

Dominant Negative ◽

Dominant Negative Mutant ◽

Eye Disc ◽

Mutant Cells ◽

Eye Imaginal Disc

By screening for Drosophila mutants exhibiting aberrant bride of sevenless (Boss) staining patterns on eye imaginal disc epithelia, we have recovered a point mutation in Hsc70-4, the closest homologue to bovine clathrin uncoating ATPase. Although the mutant allele was lethal, analysis of mutant clones generated by FLP/FRT recombination demonstrated that the Sevenless-mediated internalization of Boss was blocked in mutant Hsc70-4 eye disc epithelial cells. Endocytosis of other probes was also greatly inhibited in larval Garland cells. Immunostaining and EM analysis of the mutant cells revealed disruptions in the organization of endosomal/lysosomal compartments, including a substantial reduction in the number of clathrin-coated structures in Garland cells. The Hsc70-4 mutation also interacted genetically with a dominant-negative mutant of dynamin, a gene required for the budding of clathrin-coated vesicles (CCVs). Consistent with these phenotypes, recombinant mutant Hsc70 proteins exhibited diminished clathrin uncoating activity in vitro. Together, these data provide genetic support for the long-suspected role of Hsc70 in clathrin-mediated endocytosis, at least in part by inhibiting the uncoating of CCVs.

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frizzled regulates mirror-symmetric pattern formation in the Drosophila eye

Development ◽

10.1242/dev.121.9.3045 ◽

1995 ◽

Vol 121 (9) ◽

pp. 3045-3055 ◽

Cited By ~ 38

Author(s):

L. Zheng ◽

J. Zhang ◽

R.W. Carthew

Keyword(s):

Pattern Formation ◽

Cell Surface ◽

Transmembrane Protein ◽

Photoreceptor Cells ◽

Mirror Image ◽

Morphogenetic Furrow ◽

Symmetric Pattern ◽

Mosaic Analysis ◽

Drosophila Eye ◽

A Cell

Coordinated morphogenesis of ommatidia during Drosophila eye development establishes a mirror-image symmetric pattern across the entire eye bisected by an anteroposterior equator. We have investigated the mechanisms by which this pattern formation occurs and our results suggest that morphogenesis is coordinated by a graded signal transmitted bidirectionally from the presumptive equator to the dorsal and ventral poles. This signal is mediated by frizzled, which encodes a cell surface transmembrane protein. Mosaic analysis indicates that frizzled acts non-autonomously in an equatorial to polar direction. It also indicates that relative levels of frizzled in photoreceptor cells R3 and R4 of each ommatidium affect their positional fate choices such that the cell with greater frizzled activity becomes an R3 cell and the cell with less frizzled activity becomes an R4 cell. Moreover, this bias affects the choice an ommatidium makes as to which direction to rotate. Equator-outwards progression of elav expression and expression of the nemo gene in the morphogenetic furrow are regulated by frizzled, which itself is dynamically expressed about the morphogenetic furrow. We propose that frizzled mediates a bidirectional signal emanating from the equator.

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