Limits...
Yki/YAP, Sd/TEAD and Hth/MEIS control tissue specification in the Drosophila eye disc epithelium.

Zhang T, Zhou Q, Pignoni F - PLoS ONE (2011)

Bottom Line: RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina.On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion.Our results support a critical role for Yki- and its partners Sd and Hth--in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Center for Vision Research, and SUNY Eye Institute, SUNY Upstate Medical University, Syracuse, New York, United States of America.

ABSTRACT
During animal development, accurate control of tissue specification and growth are critical to generate organisms of reproducible shape and size. The eye-antennal disc epithelium of Drosophila is a powerful model system to identify the signaling pathway and transcription factors that mediate and coordinate these processes. We show here that the Yorkie (Yki) pathway plays a major role in tissue specification within the developing fly eye disc epithelium at a time when organ primordia and regional identity domains are specified. RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina. On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion. We also show that knockdown of the transcription factor Homothorax (Hth), known to partner Yki in some developmental contexts, also induces an ectopic retina domain, that Yki and Scalloped regulate Hth expression, and that the gain-of-function activity of Yki is partially dependent on Hth. Our results support a critical role for Yki- and its partners Sd and Hth--in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival.

Show MeSH

Related in: MedlinePlus

Loss of Yki or Sd changes the fate map of the eye disc.In all figures: posterior is on left; Gal4 driver is Act>IC>Gal4 unless otherwise stated; UAS transgenes used are as marked in panels; magnification shown in first panel applies to all panels in figure unless otherwise marked; XY images show projections of all Z optical planes unless otherwise stated; ZX and ZY images of disc scans were edited to display the selected regions of the discs marked by yellow lines in the XY view; colors have been chose to optimize image quality and do not always reflect the corresponding detection channel; for precise genotypes and temperature of crosses see Table S1. A) Schematic diagram of developing eye disc at the L3 stage with expression pattern of molecular markers used in this work. Larger image is provided in Fig. S1A. B) In the wt (top), PE cells are squamous and DP cells are columnar. In sd-RNAi-expressing discs (bottom), both cell layers display the columnar appearance of the pseudostratified DP monolayer. As shown by the uneven staining of the apical versus basal portions of the cell membranes and the position of the neuronal nuclei shown in panel D, the polarity of the cells is not disrupted; the apical side faces the disc lumen in all cases. C, D) wt (left), yki-RNAi (middle) and sd-RNAi (right) discs; C) L3 discs stained for the RDF Eya (red) to show retinal cells and the apical membrane marker E-cadherin (green) to highlight cell morphology. Mutant discs display two DP-like retina forming cell layers. D) L3 discs stained for the neuronal marker Elav (red) and the membrane marker Dlg (green). Mutant discs contain developing mirror-image, neuronal arrays; in both cell layers, neurons begin to form at the posterior and rows are added progressively expanding the ommatidial field towards the anterior.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3139632&req=5

pone-0022278-g001: Loss of Yki or Sd changes the fate map of the eye disc.In all figures: posterior is on left; Gal4 driver is Act>IC>Gal4 unless otherwise stated; UAS transgenes used are as marked in panels; magnification shown in first panel applies to all panels in figure unless otherwise marked; XY images show projections of all Z optical planes unless otherwise stated; ZX and ZY images of disc scans were edited to display the selected regions of the discs marked by yellow lines in the XY view; colors have been chose to optimize image quality and do not always reflect the corresponding detection channel; for precise genotypes and temperature of crosses see Table S1. A) Schematic diagram of developing eye disc at the L3 stage with expression pattern of molecular markers used in this work. Larger image is provided in Fig. S1A. B) In the wt (top), PE cells are squamous and DP cells are columnar. In sd-RNAi-expressing discs (bottom), both cell layers display the columnar appearance of the pseudostratified DP monolayer. As shown by the uneven staining of the apical versus basal portions of the cell membranes and the position of the neuronal nuclei shown in panel D, the polarity of the cells is not disrupted; the apical side faces the disc lumen in all cases. C, D) wt (left), yki-RNAi (middle) and sd-RNAi (right) discs; C) L3 discs stained for the RDF Eya (red) to show retinal cells and the apical membrane marker E-cadherin (green) to highlight cell morphology. Mutant discs display two DP-like retina forming cell layers. D) L3 discs stained for the neuronal marker Elav (red) and the membrane marker Dlg (green). Mutant discs contain developing mirror-image, neuronal arrays; in both cell layers, neurons begin to form at the posterior and rows are added progressively expanding the ommatidial field towards the anterior.

Mentions: The eye-antennal disc is a powerful model system for studying the genetic control of both proliferation and tissue specification. It gives rise to both neural (including several sensory organs) and non-neural fly head structures. The ‘eye’ portion of the epithelium (called eye disc) consists of a sheet of cells that gives rise to eye, ocelli (additional light-sensory organs) and cuticle of the fly head. The developing epithelium is folded into a flattened sac with two opposing cell layers separated by a lumen but continuous along much of the disc margin (Figs. 1A, S1A). During the L1 and L2 larval stages, the eye disc grows through proliferation and acquires regional identity. By the last larval stage (L3), the two layers can be readily distinguished by morphology and, within them, groups of cells are already fated to give rise to defined regions of the adult fly head (Figs. 1A, S1A). The disc proper (DP) cell layer has columnar, pseudostratified morphology, and is known to give rise to the adult eye and surrounding cuticle. The squamous peripodial portion of the epithelium (PE) is much less well understood and contributes to cuticle of the ventral and posterior regions of the fly head. Differences in morphology between the two cell layers can first be detected early in L2 (reviewed in [16]). During the L2 stage, the transcription factors Eyeless (Ey), Teashirt (Ths), Eyes absent (Eya), Sine oculis (So), and Dachshund (Dac), collectively called Retina Determination Factors (RDFs), come to be co-expressed (Ey, Tsh –>Eya –>So –>Dac) within a portion of the DP and hence define the eye or retina organ primordium. At the L3 stage, a wave of secreted factors sweeps across the DP cell layer from posterior to anterior and induces eye progenitors to stop dividing, acquire a specific cell fate and begin to differentiate into the photoreceptor neurons and accessory cells that form each single eye or ommatidium (Figs. 1A, S1A) (reviewed in [17]–[18]). Recent studies have shown that the PE contributes to the development of the DP cell layer, to the formation of several adult head structures and to the reorganization of the discs during metamorphosis (reviewed in [16]). Despite this, our understanding of the genetic control of specification, cell morphology and differentiation in the PE is still in its infancy.


Yki/YAP, Sd/TEAD and Hth/MEIS control tissue specification in the Drosophila eye disc epithelium.

Zhang T, Zhou Q, Pignoni F - PLoS ONE (2011)

Loss of Yki or Sd changes the fate map of the eye disc.In all figures: posterior is on left; Gal4 driver is Act>IC>Gal4 unless otherwise stated; UAS transgenes used are as marked in panels; magnification shown in first panel applies to all panels in figure unless otherwise marked; XY images show projections of all Z optical planes unless otherwise stated; ZX and ZY images of disc scans were edited to display the selected regions of the discs marked by yellow lines in the XY view; colors have been chose to optimize image quality and do not always reflect the corresponding detection channel; for precise genotypes and temperature of crosses see Table S1. A) Schematic diagram of developing eye disc at the L3 stage with expression pattern of molecular markers used in this work. Larger image is provided in Fig. S1A. B) In the wt (top), PE cells are squamous and DP cells are columnar. In sd-RNAi-expressing discs (bottom), both cell layers display the columnar appearance of the pseudostratified DP monolayer. As shown by the uneven staining of the apical versus basal portions of the cell membranes and the position of the neuronal nuclei shown in panel D, the polarity of the cells is not disrupted; the apical side faces the disc lumen in all cases. C, D) wt (left), yki-RNAi (middle) and sd-RNAi (right) discs; C) L3 discs stained for the RDF Eya (red) to show retinal cells and the apical membrane marker E-cadherin (green) to highlight cell morphology. Mutant discs display two DP-like retina forming cell layers. D) L3 discs stained for the neuronal marker Elav (red) and the membrane marker Dlg (green). Mutant discs contain developing mirror-image, neuronal arrays; in both cell layers, neurons begin to form at the posterior and rows are added progressively expanding the ommatidial field towards the anterior.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139632&req=5

pone-0022278-g001: Loss of Yki or Sd changes the fate map of the eye disc.In all figures: posterior is on left; Gal4 driver is Act>IC>Gal4 unless otherwise stated; UAS transgenes used are as marked in panels; magnification shown in first panel applies to all panels in figure unless otherwise marked; XY images show projections of all Z optical planes unless otherwise stated; ZX and ZY images of disc scans were edited to display the selected regions of the discs marked by yellow lines in the XY view; colors have been chose to optimize image quality and do not always reflect the corresponding detection channel; for precise genotypes and temperature of crosses see Table S1. A) Schematic diagram of developing eye disc at the L3 stage with expression pattern of molecular markers used in this work. Larger image is provided in Fig. S1A. B) In the wt (top), PE cells are squamous and DP cells are columnar. In sd-RNAi-expressing discs (bottom), both cell layers display the columnar appearance of the pseudostratified DP monolayer. As shown by the uneven staining of the apical versus basal portions of the cell membranes and the position of the neuronal nuclei shown in panel D, the polarity of the cells is not disrupted; the apical side faces the disc lumen in all cases. C, D) wt (left), yki-RNAi (middle) and sd-RNAi (right) discs; C) L3 discs stained for the RDF Eya (red) to show retinal cells and the apical membrane marker E-cadherin (green) to highlight cell morphology. Mutant discs display two DP-like retina forming cell layers. D) L3 discs stained for the neuronal marker Elav (red) and the membrane marker Dlg (green). Mutant discs contain developing mirror-image, neuronal arrays; in both cell layers, neurons begin to form at the posterior and rows are added progressively expanding the ommatidial field towards the anterior.
Mentions: The eye-antennal disc is a powerful model system for studying the genetic control of both proliferation and tissue specification. It gives rise to both neural (including several sensory organs) and non-neural fly head structures. The ‘eye’ portion of the epithelium (called eye disc) consists of a sheet of cells that gives rise to eye, ocelli (additional light-sensory organs) and cuticle of the fly head. The developing epithelium is folded into a flattened sac with two opposing cell layers separated by a lumen but continuous along much of the disc margin (Figs. 1A, S1A). During the L1 and L2 larval stages, the eye disc grows through proliferation and acquires regional identity. By the last larval stage (L3), the two layers can be readily distinguished by morphology and, within them, groups of cells are already fated to give rise to defined regions of the adult fly head (Figs. 1A, S1A). The disc proper (DP) cell layer has columnar, pseudostratified morphology, and is known to give rise to the adult eye and surrounding cuticle. The squamous peripodial portion of the epithelium (PE) is much less well understood and contributes to cuticle of the ventral and posterior regions of the fly head. Differences in morphology between the two cell layers can first be detected early in L2 (reviewed in [16]). During the L2 stage, the transcription factors Eyeless (Ey), Teashirt (Ths), Eyes absent (Eya), Sine oculis (So), and Dachshund (Dac), collectively called Retina Determination Factors (RDFs), come to be co-expressed (Ey, Tsh –>Eya –>So –>Dac) within a portion of the DP and hence define the eye or retina organ primordium. At the L3 stage, a wave of secreted factors sweeps across the DP cell layer from posterior to anterior and induces eye progenitors to stop dividing, acquire a specific cell fate and begin to differentiate into the photoreceptor neurons and accessory cells that form each single eye or ommatidium (Figs. 1A, S1A) (reviewed in [17]–[18]). Recent studies have shown that the PE contributes to the development of the DP cell layer, to the formation of several adult head structures and to the reorganization of the discs during metamorphosis (reviewed in [16]). Despite this, our understanding of the genetic control of specification, cell morphology and differentiation in the PE is still in its infancy.

Bottom Line: RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina.On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion.Our results support a critical role for Yki- and its partners Sd and Hth--in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Center for Vision Research, and SUNY Eye Institute, SUNY Upstate Medical University, Syracuse, New York, United States of America.

ABSTRACT
During animal development, accurate control of tissue specification and growth are critical to generate organisms of reproducible shape and size. The eye-antennal disc epithelium of Drosophila is a powerful model system to identify the signaling pathway and transcription factors that mediate and coordinate these processes. We show here that the Yorkie (Yki) pathway plays a major role in tissue specification within the developing fly eye disc epithelium at a time when organ primordia and regional identity domains are specified. RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina. On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion. We also show that knockdown of the transcription factor Homothorax (Hth), known to partner Yki in some developmental contexts, also induces an ectopic retina domain, that Yki and Scalloped regulate Hth expression, and that the gain-of-function activity of Yki is partially dependent on Hth. Our results support a critical role for Yki- and its partners Sd and Hth--in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival.

Show MeSH
Related in: MedlinePlus