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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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Related in: MedlinePlus

Yki, Sd and Hth functions in different regions of the L2 eye disc.In this model, different combinations of co-factors associate with Yki to bring about different outcomes in distinct regions of the L2 eye disc epithelium. A Yki/Hth/Tsh complex would ensures the maintenance and expansion of the retina progenitors pool in the DP cell layer by promoting proliferation and suppressing apoptosis; whereas, in the PE, Hth is first induced by, and then would work in concert with, Yki and Sd to control regional specification by suppressing retina identity and promoting development of PE derivatives (this work). The induction of Hth by Yki/Sd could be direct or indirect (dashed arrow), whereas the negative regulation of one or more genes of the RD network would have to be, at least in part, indirect based on the non-cell-autonomous features of mutant clones. Whether Yki, together with Tsh and/or other partners, controls proliferation and survival of the more developmentally advanced ‘Eya-positive + Hth-negative’ retina progenitors (named here “eye precursor” cells) is likely, based on the small size of yki-RNAi expressing clones from this region of the disc, but requires further testing. Though not shown in this diagram for simplicity, Ey is also expressed throughout the PE and Eya is expressed in a restricted posterior-lateral portion of the PE, in the L2 eye disc; as shown, Tsh is detected only in the DP cell layer.
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pone-0022278-g007: Yki, Sd and Hth functions in different regions of the L2 eye disc.In this model, different combinations of co-factors associate with Yki to bring about different outcomes in distinct regions of the L2 eye disc epithelium. A Yki/Hth/Tsh complex would ensures the maintenance and expansion of the retina progenitors pool in the DP cell layer by promoting proliferation and suppressing apoptosis; whereas, in the PE, Hth is first induced by, and then would work in concert with, Yki and Sd to control regional specification by suppressing retina identity and promoting development of PE derivatives (this work). The induction of Hth by Yki/Sd could be direct or indirect (dashed arrow), whereas the negative regulation of one or more genes of the RD network would have to be, at least in part, indirect based on the non-cell-autonomous features of mutant clones. Whether Yki, together with Tsh and/or other partners, controls proliferation and survival of the more developmentally advanced ‘Eya-positive + Hth-negative’ retina progenitors (named here “eye precursor” cells) is likely, based on the small size of yki-RNAi expressing clones from this region of the disc, but requires further testing. Though not shown in this diagram for simplicity, Ey is also expressed throughout the PE and Eya is expressed in a restricted posterior-lateral portion of the PE, in the L2 eye disc; as shown, Tsh is detected only in the DP cell layer.

Mentions: Yki association with specific co-factors would, therefore, modify the output of the Hpo-Yki pathway to bring about different outcomes in distinct regions of the eye epithelium. A Yki/Hth/Tsh complex would ensure maintenance and expansion of the retina progenitors pool [14], whereas a Yki/Sd, and possibly Hth, complex would contribute to regional specification within the eye disc by ensuring formation of PE-derived head structures (this work) (Fig. 7). That Yki/YAP-based complexes can include a variety of different co-factors is supported by other recent examples, including the above mentioned role of Yki, Hth and Tsh in promoting eye progenitors' proliferation in the fly [14], and its interaction with IRS1 [48] to promote proliferation of neural precursors or with Smad1 [49] to enhance BMP-mediated suppression of neuronal differentiation of embryonic stem cells in the mouse.


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)

Yki, Sd and Hth functions in different regions of the L2 eye disc.In this model, different combinations of co-factors associate with Yki to bring about different outcomes in distinct regions of the L2 eye disc epithelium. A Yki/Hth/Tsh complex would ensures the maintenance and expansion of the retina progenitors pool in the DP cell layer by promoting proliferation and suppressing apoptosis; whereas, in the PE, Hth is first induced by, and then would work in concert with, Yki and Sd to control regional specification by suppressing retina identity and promoting development of PE derivatives (this work). The induction of Hth by Yki/Sd could be direct or indirect (dashed arrow), whereas the negative regulation of one or more genes of the RD network would have to be, at least in part, indirect based on the non-cell-autonomous features of mutant clones. Whether Yki, together with Tsh and/or other partners, controls proliferation and survival of the more developmentally advanced ‘Eya-positive + Hth-negative’ retina progenitors (named here “eye precursor” cells) is likely, based on the small size of yki-RNAi expressing clones from this region of the disc, but requires further testing. Though not shown in this diagram for simplicity, Ey is also expressed throughout the PE and Eya is expressed in a restricted posterior-lateral portion of the PE, in the L2 eye disc; as shown, Tsh is detected only in the DP cell layer.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3139632&req=5

pone-0022278-g007: Yki, Sd and Hth functions in different regions of the L2 eye disc.In this model, different combinations of co-factors associate with Yki to bring about different outcomes in distinct regions of the L2 eye disc epithelium. A Yki/Hth/Tsh complex would ensures the maintenance and expansion of the retina progenitors pool in the DP cell layer by promoting proliferation and suppressing apoptosis; whereas, in the PE, Hth is first induced by, and then would work in concert with, Yki and Sd to control regional specification by suppressing retina identity and promoting development of PE derivatives (this work). The induction of Hth by Yki/Sd could be direct or indirect (dashed arrow), whereas the negative regulation of one or more genes of the RD network would have to be, at least in part, indirect based on the non-cell-autonomous features of mutant clones. Whether Yki, together with Tsh and/or other partners, controls proliferation and survival of the more developmentally advanced ‘Eya-positive + Hth-negative’ retina progenitors (named here “eye precursor” cells) is likely, based on the small size of yki-RNAi expressing clones from this region of the disc, but requires further testing. Though not shown in this diagram for simplicity, Ey is also expressed throughout the PE and Eya is expressed in a restricted posterior-lateral portion of the PE, in the L2 eye disc; as shown, Tsh is detected only in the DP cell layer.
Mentions: Yki association with specific co-factors would, therefore, modify the output of the Hpo-Yki pathway to bring about different outcomes in distinct regions of the eye epithelium. A Yki/Hth/Tsh complex would ensure maintenance and expansion of the retina progenitors pool [14], whereas a Yki/Sd, and possibly Hth, complex would contribute to regional specification within the eye disc by ensuring formation of PE-derived head structures (this work) (Fig. 7). That Yki/YAP-based complexes can include a variety of different co-factors is supported by other recent examples, including the above mentioned role of Yki, Hth and Tsh in promoting eye progenitors' proliferation in the fly [14], and its interaction with IRS1 [48] to promote proliferation of neural precursors or with Smad1 [49] to enhance BMP-mediated suppression of neuronal differentiation of embryonic stem cells in the mouse.

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