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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.

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Hth controls PE formation and its expression is regulated by Yki and Sd.A) Wild type L3 disc stained for Hth (red) and Dlg (green); top: XY view of PE layer; middle: XZ view of disc. Bottom: XY view of DP layer. Notice that Hth is broadly expressed in both PE and DP cell layers, but is excluded from part of the eye field. B) ZX views of hth-RNAi expressing discs stained for Eya (red) and E-cadherin (green) (top) or for Elav (red) and Dlg (green) (bottom). Discs show the transformation of PE into a DP with an ectopic retina field (Eya-positive cells) and ectopic neuronal development (Elav-positive clusters). C) ZX views of L3 eye discs expressing an exogenous Hth-GFP fusion protein throughout (left), Hth-GFP plus sd-RNAi (middle), or Hth-GFP plus yki-RNAi (right) stained for anti-GFP (green) to detect Hth-GFP, Eya (red) and Elav (blue). No expression of Eya, or Elav is detected. Co-expression of sd-RNAi or yki-RNAi does not rescue the loss of retina due to Hth mis-expression. D) Top: ZX views of Yki-expressing L3 eye disc stained for Hth (red) and Dlg (green). Over-expression of Yki induces ectopic Hth expression (compare to panel A). Bottom: ZX views of sd-RNAi-expressing L3 eye disc stained for Hth (red) and UAS-GFP (blue). Down-regulation of Sd in cell marked by GFP results in loss of Hth expression. This is consistent with the development of an ectopic retina within the transformed PE as shown in panel B.
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pone-0022278-g004: Hth controls PE formation and its expression is regulated by Yki and Sd.A) Wild type L3 disc stained for Hth (red) and Dlg (green); top: XY view of PE layer; middle: XZ view of disc. Bottom: XY view of DP layer. Notice that Hth is broadly expressed in both PE and DP cell layers, but is excluded from part of the eye field. B) ZX views of hth-RNAi expressing discs stained for Eya (red) and E-cadherin (green) (top) or for Elav (red) and Dlg (green) (bottom). Discs show the transformation of PE into a DP with an ectopic retina field (Eya-positive cells) and ectopic neuronal development (Elav-positive clusters). C) ZX views of L3 eye discs expressing an exogenous Hth-GFP fusion protein throughout (left), Hth-GFP plus sd-RNAi (middle), or Hth-GFP plus yki-RNAi (right) stained for anti-GFP (green) to detect Hth-GFP, Eya (red) and Elav (blue). No expression of Eya, or Elav is detected. Co-expression of sd-RNAi or yki-RNAi does not rescue the loss of retina due to Hth mis-expression. D) Top: ZX views of Yki-expressing L3 eye disc stained for Hth (red) and Dlg (green). Over-expression of Yki induces ectopic Hth expression (compare to panel A). Bottom: ZX views of sd-RNAi-expressing L3 eye disc stained for Hth (red) and UAS-GFP (blue). Down-regulation of Sd in cell marked by GFP results in loss of Hth expression. This is consistent with the development of an ectopic retina within the transformed PE as shown in panel B.

Mentions: Recently, another DNA-binding transcription factor has been implicated in Yki-regulated gene expression. Mann and colleagues have shown that the homeobox protein Homeothorax (Hth) and Yki bind in vitro and directly regulate transcription of the gene Bantam in eye progenitor cells [14]. Since Hth is also expressed throughout the PE cell layer [23](Fig. 4A) and its mis-expression in the DP can suppress eye morphogenesis (assessed through Eya and Elav expression) [24], [25], we decided to investigate whether Hth plays a role in PE formation.


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)

Hth controls PE formation and its expression is regulated by Yki and Sd.A) Wild type L3 disc stained for Hth (red) and Dlg (green); top: XY view of PE layer; middle: XZ view of disc. Bottom: XY view of DP layer. Notice that Hth is broadly expressed in both PE and DP cell layers, but is excluded from part of the eye field. B) ZX views of hth-RNAi expressing discs stained for Eya (red) and E-cadherin (green) (top) or for Elav (red) and Dlg (green) (bottom). Discs show the transformation of PE into a DP with an ectopic retina field (Eya-positive cells) and ectopic neuronal development (Elav-positive clusters). C) ZX views of L3 eye discs expressing an exogenous Hth-GFP fusion protein throughout (left), Hth-GFP plus sd-RNAi (middle), or Hth-GFP plus yki-RNAi (right) stained for anti-GFP (green) to detect Hth-GFP, Eya (red) and Elav (blue). No expression of Eya, or Elav is detected. Co-expression of sd-RNAi or yki-RNAi does not rescue the loss of retina due to Hth mis-expression. D) Top: ZX views of Yki-expressing L3 eye disc stained for Hth (red) and Dlg (green). Over-expression of Yki induces ectopic Hth expression (compare to panel A). Bottom: ZX views of sd-RNAi-expressing L3 eye disc stained for Hth (red) and UAS-GFP (blue). Down-regulation of Sd in cell marked by GFP results in loss of Hth expression. This is consistent with the development of an ectopic retina within the transformed PE as shown in panel B.
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Related In: Results  -  Collection

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pone-0022278-g004: Hth controls PE formation and its expression is regulated by Yki and Sd.A) Wild type L3 disc stained for Hth (red) and Dlg (green); top: XY view of PE layer; middle: XZ view of disc. Bottom: XY view of DP layer. Notice that Hth is broadly expressed in both PE and DP cell layers, but is excluded from part of the eye field. B) ZX views of hth-RNAi expressing discs stained for Eya (red) and E-cadherin (green) (top) or for Elav (red) and Dlg (green) (bottom). Discs show the transformation of PE into a DP with an ectopic retina field (Eya-positive cells) and ectopic neuronal development (Elav-positive clusters). C) ZX views of L3 eye discs expressing an exogenous Hth-GFP fusion protein throughout (left), Hth-GFP plus sd-RNAi (middle), or Hth-GFP plus yki-RNAi (right) stained for anti-GFP (green) to detect Hth-GFP, Eya (red) and Elav (blue). No expression of Eya, or Elav is detected. Co-expression of sd-RNAi or yki-RNAi does not rescue the loss of retina due to Hth mis-expression. D) Top: ZX views of Yki-expressing L3 eye disc stained for Hth (red) and Dlg (green). Over-expression of Yki induces ectopic Hth expression (compare to panel A). Bottom: ZX views of sd-RNAi-expressing L3 eye disc stained for Hth (red) and UAS-GFP (blue). Down-regulation of Sd in cell marked by GFP results in loss of Hth expression. This is consistent with the development of an ectopic retina within the transformed PE as shown in panel B.
Mentions: Recently, another DNA-binding transcription factor has been implicated in Yki-regulated gene expression. Mann and colleagues have shown that the homeobox protein Homeothorax (Hth) and Yki bind in vitro and directly regulate transcription of the gene Bantam in eye progenitor cells [14]. Since Hth is also expressed throughout the PE cell layer [23](Fig. 4A) and its mis-expression in the DP can suppress eye morphogenesis (assessed through Eya and Elav expression) [24], [25], we decided to investigate whether Hth plays a role in PE formation.

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