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

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

Development ◽

10.1242/dev.124.17.3233 ◽

1997 ◽

Vol 124 (17) ◽

pp. 3233-3240 ◽

Cited By ~ 11

Author(s):

D.I. Strutt ◽

M. Mlodzik

Keyword(s):

Pattern Formation ◽

Imaginal Disc ◽

Morphogenetic Furrow ◽

Anterior Edge ◽

Eye Disc ◽

Drosophila Eye ◽

Eye Imaginal Disc ◽

Inductive Signal ◽

Rate Of Movement

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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decapentaplegic and wingless are regulated by eyes absent and eyegone and interact to direct the pattern of retinal differentiation in the eye disc

Development ◽

10.1242/dev.125.18.3741 ◽

1998 ◽

Vol 125 (18) ◽

pp. 3741-3751 ◽

Cited By ~ 26

Author(s):

D.J. Hazelett ◽

M. Bourouis ◽

U. Walldorf ◽

J.E. Treisman

Keyword(s):

Posterior Margin ◽

Imaginal Disc ◽

Anterior Margin ◽

Growth Factor Receptor ◽

Eyes Absent ◽

Retinal Tissue ◽

Eye Disc ◽

Epidermal Growth ◽

Lateral Margins ◽

Eye Imaginal Disc

Signaling by the secreted hedgehog, decapentaplegic and wingless proteins organizes the pattern of photoreceptor differentiation within the Drosophila eye imaginal disc; hedgehog and decapentaplegic are required for differentiation to initiate at the posterior margin and progress across the disc, while wingless prevents it from initiating at the lateral margins. Our analysis of these interactions has shown that initiation requires both the presence of decapentaplegic and the absence of wingless, which inhibits photoreceptor differentiation downstream of the reception of the decapentaplegic signal. However, wingless is unable to inhibit differentiation driven by activation of the epidermal growth factor receptor pathway. The effect of wingless is subject to regional variations in control, as the anterior margin of the disc is insensitive to wingless inhibition. The eyes absent and eyegone genes encode members of a group of nuclear proteins required to specify the fate of the eye imaginal disc. We show that both eyes absent and eyegone are required for normal activation of decapentaplegic expression at the posterior and lateral margins of the disc, and repression of wingless expression in presumptive retinal tissue. The requirement for eyegone can be alleviated by inhibition of the wingless signaling pathway, suggesting that eyegone promotes eye development primarily by repressing wingless. These results provide a link between the early specification and later differentiation of the eye disc.

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dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila

Development ◽

10.1242/dev.120.12.3473 ◽

1994 ◽

Vol 120 (12) ◽

pp. 3473-3486 ◽

Cited By ~ 42

Author(s):

G. Mardon ◽

N.M. Solomon ◽

G.M. Rubin

Keyword(s):

Cell Fate ◽

Posterior Margin ◽

Imaginal Disc ◽

Nuclear Protein ◽

Eye Disc ◽

Leg Development ◽

Disc Cells ◽

Neural Specification ◽

Eye Imaginal Disc

Neural specification and differentiation in the Drosophila eye sweep across the unpatterned epithelial monolayer of the eye imaginal disc following a developmental wave termed the morphogenetic furrow. The furrow begins at the posterior margin of the eye imaginal disc and moves anteriorly as a linear front. Progression of the furrow requires the function of hedgehog, which encodes a secreted signaling protein. We characterize mutations in dachshund, a gene that encodes a novel nuclear protein required for normal cell-fate determination of imaginal disc cells. In the absence of dachshund function, cells at the posterior margin of the eye disc fail to follow a retinal differentiation pathway and appear to adopt a cuticle fate instead. These cells are therefore unable to respond to pattern propagation signals such as hedgehog and furrow initiation does not occur. In contrast, cells in more anterior portions of the eye disc are able to differentiate as retinal cells in the absence of dachshund activity and respond normally to patterning signals. These results suggest that posterior margin cells are distinct from other cells of the eye imaginal disc by early stages of development. dachshund is also necessary for proper differentiation of a subset of segments in the developing leg. Null mutations in dachshund result in flies with no eyes and shortened legs.

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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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Analysis of Drosophila Cyclin EI and II Function during Development: Identification of an Inhibitory Zone within the Morphogenetic Furrow of the Eye Imaginal Disc That Blocks the Function of Cyclin EI but Not Cyclin EII

Developmental Biology ◽

10.1006/dbio.2001.0496 ◽

2002 ◽

Vol 241 (1) ◽

pp. 157-171 ◽

Cited By ~ 10

Author(s):

Donna Crack ◽

Julie Secombe ◽

Michelle Coombe ◽

Anthony Brumby ◽

Robert Saint ◽

...

Keyword(s):

Imaginal Disc ◽

Morphogenetic Furrow ◽

Inhibitory Zone ◽

Eye Imaginal Disc

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Morphogenetic processes as data: Quantitative structure in the Drosophila eye imaginal disc

10.1101/395640 ◽

2018 ◽

Author(s):

Bradly Alicea ◽

Thomas E. Portegys ◽

Diana Gordon ◽

Richard Gordon

Keyword(s):

Mathematical Modeling ◽

High Resolution ◽

Imaginal Disc ◽

Biological Theory ◽

Biological Processes ◽

Quantitative Structure ◽

Morphogenetic Furrow ◽

High Resolution Image ◽

New Information ◽

Eye Imaginal Disc

AbstractWe can improve our understanding of biological processes through the use of computational and mathematical modeling. One such morphogenetic process (ommatidia formation in the Drosophila eye imaginal disc) provides us with an opportunity to demonstrate the power of this approach. We use a high-resolution image that catches the spatially- and temporally-dependent process of ommatidia formation in the act. This image is converted to quantitative measures and models that provide us with new information about the dynamics and geometry of this process. We approach this by addressing three computational hypotheses, and provide a publicly-available repository containing data and images for further analysis. Potential spatial patterns in the morphogenetic furrow and ommatidia are summarized, while the ommatidia cells are projected to a spherical map in order to identify higher-level spatiotemporal features. In the conclusion, we discuss the implications of our approach and findings for developmental complexity and biological theory.

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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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