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Dynamic rewiring of the Drosophila retinal determination network switches its function from selector to differentiation.

Atkins M, Jiang Y, Sansores-Garcia L, Jusiak B, Halder G, Mardon G - PLoS Genet. (2013)

Bottom Line: Organ development is directed by selector gene networks.We found that central to the transition is a switch from positive regulation of ey transcription to negative regulation and that both types of regulation require so.We conclude that changes in the regulatory relationships among members of the retinal determination gene network are a driving force for key transitions in retinal development.

View Article: PubMed Central - PubMed

Affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.

ABSTRACT
Organ development is directed by selector gene networks. Eye development in the fruit fly Drosophila melanogaster is driven by the highly conserved selector gene network referred to as the "retinal determination gene network," composed of approximately 20 factors, whose core comprises twin of eyeless (toy), eyeless (ey), sine oculis (so), dachshund (dac), and eyes absent (eya). These genes encode transcriptional regulators that are each necessary for normal eye development, and sufficient to direct ectopic eye development when misexpressed. While it is well documented that the downstream genes so, eya, and dac are necessary not only during early growth and determination stages but also during the differentiation phase of retinal development, it remains unknown how the retinal determination gene network terminates its functions in determination and begins to promote differentiation. Here, we identify a switch in the regulation of ey by the downstream retinal determination genes, which is essential for the transition from determination to differentiation. We found that central to the transition is a switch from positive regulation of ey transcription to negative regulation and that both types of regulation require so. Our results suggest a model in which the retinal determination gene network is rewired to end the growth and determination stage of eye development and trigger terminal differentiation. We conclude that changes in the regulatory relationships among members of the retinal determination gene network are a driving force for key transitions in retinal development.

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Ey repression at the morphogenetic furrow is necessary for differentiation.(A) Cubitus interruptus (Ci), Eyeless (Ey), and Senseless (Sens) expression in a w1118 third instar eye-antennal imaginal disc. (A′) Strong Ci accumulation marks the morphogenetic furrow. (A″) Ey expression; white arrow marks cuboidal margin cells, yellow asterisk marks ventral head capsule. (A′″) Sens expression shows R8 differentiation. (B–D) Yellow arrow marks the morphogenetic furrow: (B) Sine oculis (So) expression, (C) Eyes absent (Eya) expression, (D) Dachshund (Dac) expression. (E) Overexpression of Ey posterior to the morphogenetic furrow using Flipout-Gal4 inhibits photoreceptor differentiation. (E′) ELAV from panel E showing differentiation. (E″) Eyeless expression from panel E.
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pgen-1003731-g001: Ey repression at the morphogenetic furrow is necessary for differentiation.(A) Cubitus interruptus (Ci), Eyeless (Ey), and Senseless (Sens) expression in a w1118 third instar eye-antennal imaginal disc. (A′) Strong Ci accumulation marks the morphogenetic furrow. (A″) Ey expression; white arrow marks cuboidal margin cells, yellow asterisk marks ventral head capsule. (A′″) Sens expression shows R8 differentiation. (B–D) Yellow arrow marks the morphogenetic furrow: (B) Sine oculis (So) expression, (C) Eyes absent (Eya) expression, (D) Dachshund (Dac) expression. (E) Overexpression of Ey posterior to the morphogenetic furrow using Flipout-Gal4 inhibits photoreceptor differentiation. (E′) ELAV from panel E showing differentiation. (E″) Eyeless expression from panel E.

Mentions: Selector genes direct the development of many organs from their primordia [8]. The development of the eye imaginal disc into the adult eye is directed by a conserved network of transcriptional regulators called the retinal determination (RD) gene network. The core members of this network, twin of eyeless (toy), eyeless (ey), sine oculis (so), eyes absent (eya), and dachshund (dac), are each necessary for normal eye development and are sufficient to drive ectopic eye development in other imaginal discs [9]–[17]. During normal development, Toy activates ey expression in the first instar [17]. Initially, Ey is expressed throughout the disc and activates the expression of eya, so, and dac[18]–[21]. Once established, So maintains its own expression, as well as that of dac and ey[19], [22]. Such positive feedback mechanisms within the network are well characterized [17]–[19], [23]–[25]. The downstream RD network members Eya, So, and Dac are expressed and necessary in cells posterior to the morphogenetic furrow (Figure 1B–D) [9]–[13], [22], [26]. In contrast, at the morphogenetic furrow, ey expression is sharply down-regulated (Figure 1A), but how the positive feedback loops are terminated remains unknown [14], [18].


Dynamic rewiring of the Drosophila retinal determination network switches its function from selector to differentiation.

Atkins M, Jiang Y, Sansores-Garcia L, Jusiak B, Halder G, Mardon G - PLoS Genet. (2013)

Ey repression at the morphogenetic furrow is necessary for differentiation.(A) Cubitus interruptus (Ci), Eyeless (Ey), and Senseless (Sens) expression in a w1118 third instar eye-antennal imaginal disc. (A′) Strong Ci accumulation marks the morphogenetic furrow. (A″) Ey expression; white arrow marks cuboidal margin cells, yellow asterisk marks ventral head capsule. (A′″) Sens expression shows R8 differentiation. (B–D) Yellow arrow marks the morphogenetic furrow: (B) Sine oculis (So) expression, (C) Eyes absent (Eya) expression, (D) Dachshund (Dac) expression. (E) Overexpression of Ey posterior to the morphogenetic furrow using Flipout-Gal4 inhibits photoreceptor differentiation. (E′) ELAV from panel E showing differentiation. (E″) Eyeless expression from panel E.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3757064&req=5

pgen-1003731-g001: Ey repression at the morphogenetic furrow is necessary for differentiation.(A) Cubitus interruptus (Ci), Eyeless (Ey), and Senseless (Sens) expression in a w1118 third instar eye-antennal imaginal disc. (A′) Strong Ci accumulation marks the morphogenetic furrow. (A″) Ey expression; white arrow marks cuboidal margin cells, yellow asterisk marks ventral head capsule. (A′″) Sens expression shows R8 differentiation. (B–D) Yellow arrow marks the morphogenetic furrow: (B) Sine oculis (So) expression, (C) Eyes absent (Eya) expression, (D) Dachshund (Dac) expression. (E) Overexpression of Ey posterior to the morphogenetic furrow using Flipout-Gal4 inhibits photoreceptor differentiation. (E′) ELAV from panel E showing differentiation. (E″) Eyeless expression from panel E.
Mentions: Selector genes direct the development of many organs from their primordia [8]. The development of the eye imaginal disc into the adult eye is directed by a conserved network of transcriptional regulators called the retinal determination (RD) gene network. The core members of this network, twin of eyeless (toy), eyeless (ey), sine oculis (so), eyes absent (eya), and dachshund (dac), are each necessary for normal eye development and are sufficient to drive ectopic eye development in other imaginal discs [9]–[17]. During normal development, Toy activates ey expression in the first instar [17]. Initially, Ey is expressed throughout the disc and activates the expression of eya, so, and dac[18]–[21]. Once established, So maintains its own expression, as well as that of dac and ey[19], [22]. Such positive feedback mechanisms within the network are well characterized [17]–[19], [23]–[25]. The downstream RD network members Eya, So, and Dac are expressed and necessary in cells posterior to the morphogenetic furrow (Figure 1B–D) [9]–[13], [22], [26]. In contrast, at the morphogenetic furrow, ey expression is sharply down-regulated (Figure 1A), but how the positive feedback loops are terminated remains unknown [14], [18].

Bottom Line: Organ development is directed by selector gene networks.We found that central to the transition is a switch from positive regulation of ey transcription to negative regulation and that both types of regulation require so.We conclude that changes in the regulatory relationships among members of the retinal determination gene network are a driving force for key transitions in retinal development.

View Article: PubMed Central - PubMed

Affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.

ABSTRACT
Organ development is directed by selector gene networks. Eye development in the fruit fly Drosophila melanogaster is driven by the highly conserved selector gene network referred to as the "retinal determination gene network," composed of approximately 20 factors, whose core comprises twin of eyeless (toy), eyeless (ey), sine oculis (so), dachshund (dac), and eyes absent (eya). These genes encode transcriptional regulators that are each necessary for normal eye development, and sufficient to direct ectopic eye development when misexpressed. While it is well documented that the downstream genes so, eya, and dac are necessary not only during early growth and determination stages but also during the differentiation phase of retinal development, it remains unknown how the retinal determination gene network terminates its functions in determination and begins to promote differentiation. Here, we identify a switch in the regulation of ey by the downstream retinal determination genes, which is essential for the transition from determination to differentiation. We found that central to the transition is a switch from positive regulation of ey transcription to negative regulation and that both types of regulation require so. Our results suggest a model in which the retinal determination gene network is rewired to end the growth and determination stage of eye development and trigger terminal differentiation. We conclude that changes in the regulatory relationships among members of the retinal determination gene network are a driving force for key transitions in retinal development.

Show MeSH
Related in: MedlinePlus