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Robustness and stability of the gene regulatory network involved in DV boundary formation in the Drosophila wing.

Buceta J, Herranz H, Canela-Xandri O, Reigada R, Sagués F, Milán M - PLoS ONE (2007)

Bottom Line: By means of a Systems Biology approach that combines mathematical modeling and both in silico and in vivo experiments in the Drosophila wing primordium, we modeled and tested this regulatory network and present evidence that a novel property, namely refractoriness to the Wingless signaling molecule, is required in boundary cells for the formation of a stable dorsal-ventral boundary.This new property has been validated in vivo, promotes mutually exclusive domains of Notch and Wingless activities and confers stability to the dorsal-ventral boundary.A robustness analysis of the regulatory network complements our results and ensures its biological plausibility.

View Article: PubMed Central - PubMed

Affiliation: Centre especial de Recerca en Química Teòrica (CeRQT), Parc Científic de Barcelona, Barcelona, Spain. jbuceta@pcb.ub.es

ABSTRACT
Gene regulatory networks have been conserved during evolution. The Drosophila wing and the vertebrate hindbrain share the gene network involved in the establishment of the boundary between dorsal and ventral compartments in the wing and adjacent rhombomeres in the hindbrain. A positive feedback-loop between boundary and non-boundary cells and mediated by the activities of Notch and Wingless/Wnt-1 leads to the establishment of a Notch dependent organizer at the boundary. By means of a Systems Biology approach that combines mathematical modeling and both in silico and in vivo experiments in the Drosophila wing primordium, we modeled and tested this regulatory network and present evidence that a novel property, namely refractoriness to the Wingless signaling molecule, is required in boundary cells for the formation of a stable dorsal-ventral boundary. This new property has been validated in vivo, promotes mutually exclusive domains of Notch and Wingless activities and confers stability to the dorsal-ventral boundary. A robustness analysis of the regulatory network complements our results and ensures its biological plausibility.

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Gene regulatory network involved in DV boundary formation.(A) The wing primordium (left) is subdivided into anterior (A) and posterior (P) compartments, as well as into dorsal (D) and ventral (V) compartments, which will give rise to specific biological structures within the adult wing (right). The compartments are named after the position that their cells and progeny will occupy by the end of development. (B, C) Early in development (B), Serrate (Ser) signals to V cells to activate Notch (N). Likewise, Delta (Dl) signals to D cells to activate Notch modified by Fringe (Fng) along the DV boundary. Later in development (C), ligands expression becomes symmetric with respect to the boundary and a positive feedback-loop between Wingless (Wg) and Ser/Dl-expressing cells maintains the signaling center along the DV boundary. Notch activity elicits Cut expression that represses Dl and Ser in boundary cells.
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pone-0000602-g001: Gene regulatory network involved in DV boundary formation.(A) The wing primordium (left) is subdivided into anterior (A) and posterior (P) compartments, as well as into dorsal (D) and ventral (V) compartments, which will give rise to specific biological structures within the adult wing (right). The compartments are named after the position that their cells and progeny will occupy by the end of development. (B, C) Early in development (B), Serrate (Ser) signals to V cells to activate Notch (N). Likewise, Delta (Dl) signals to D cells to activate Notch modified by Fringe (Fng) along the DV boundary. Later in development (C), ligands expression becomes symmetric with respect to the boundary and a positive feedback-loop between Wingless (Wg) and Ser/Dl-expressing cells maintains the signaling center along the DV boundary. Notch activity elicits Cut expression that represses Dl and Ser in boundary cells.

Mentions: The wing primordium of Drosophila and the rhombomeres of the vertebrate hindbrain provide well-characterized examples in which domains of gene expression, modulated by short and long-range cell interactions, link to well-defined biological structures. Both systems become subdivided into stable cell populations called compartments, which do not mix during development ([2], [3], Figure 1A). Compartment subdivision is induced primarily by the specific expression and activity of transcription factors that confer a compartment specific fate (reviewed in [4]). Short-range cell interactions between adjacent compartments lead to the expression of long-range signaling molecules at the compartment boundaries, thus serving these boundaries as signaling centers with long-range organizing properties.


Robustness and stability of the gene regulatory network involved in DV boundary formation in the Drosophila wing.

Buceta J, Herranz H, Canela-Xandri O, Reigada R, Sagués F, Milán M - PLoS ONE (2007)

Gene regulatory network involved in DV boundary formation.(A) The wing primordium (left) is subdivided into anterior (A) and posterior (P) compartments, as well as into dorsal (D) and ventral (V) compartments, which will give rise to specific biological structures within the adult wing (right). The compartments are named after the position that their cells and progeny will occupy by the end of development. (B, C) Early in development (B), Serrate (Ser) signals to V cells to activate Notch (N). Likewise, Delta (Dl) signals to D cells to activate Notch modified by Fringe (Fng) along the DV boundary. Later in development (C), ligands expression becomes symmetric with respect to the boundary and a positive feedback-loop between Wingless (Wg) and Ser/Dl-expressing cells maintains the signaling center along the DV boundary. Notch activity elicits Cut expression that represses Dl and Ser in boundary cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1904254&req=5

pone-0000602-g001: Gene regulatory network involved in DV boundary formation.(A) The wing primordium (left) is subdivided into anterior (A) and posterior (P) compartments, as well as into dorsal (D) and ventral (V) compartments, which will give rise to specific biological structures within the adult wing (right). The compartments are named after the position that their cells and progeny will occupy by the end of development. (B, C) Early in development (B), Serrate (Ser) signals to V cells to activate Notch (N). Likewise, Delta (Dl) signals to D cells to activate Notch modified by Fringe (Fng) along the DV boundary. Later in development (C), ligands expression becomes symmetric with respect to the boundary and a positive feedback-loop between Wingless (Wg) and Ser/Dl-expressing cells maintains the signaling center along the DV boundary. Notch activity elicits Cut expression that represses Dl and Ser in boundary cells.
Mentions: The wing primordium of Drosophila and the rhombomeres of the vertebrate hindbrain provide well-characterized examples in which domains of gene expression, modulated by short and long-range cell interactions, link to well-defined biological structures. Both systems become subdivided into stable cell populations called compartments, which do not mix during development ([2], [3], Figure 1A). Compartment subdivision is induced primarily by the specific expression and activity of transcription factors that confer a compartment specific fate (reviewed in [4]). Short-range cell interactions between adjacent compartments lead to the expression of long-range signaling molecules at the compartment boundaries, thus serving these boundaries as signaling centers with long-range organizing properties.

Bottom Line: By means of a Systems Biology approach that combines mathematical modeling and both in silico and in vivo experiments in the Drosophila wing primordium, we modeled and tested this regulatory network and present evidence that a novel property, namely refractoriness to the Wingless signaling molecule, is required in boundary cells for the formation of a stable dorsal-ventral boundary.This new property has been validated in vivo, promotes mutually exclusive domains of Notch and Wingless activities and confers stability to the dorsal-ventral boundary.A robustness analysis of the regulatory network complements our results and ensures its biological plausibility.

View Article: PubMed Central - PubMed

Affiliation: Centre especial de Recerca en Química Teòrica (CeRQT), Parc Científic de Barcelona, Barcelona, Spain. jbuceta@pcb.ub.es

ABSTRACT
Gene regulatory networks have been conserved during evolution. The Drosophila wing and the vertebrate hindbrain share the gene network involved in the establishment of the boundary between dorsal and ventral compartments in the wing and adjacent rhombomeres in the hindbrain. A positive feedback-loop between boundary and non-boundary cells and mediated by the activities of Notch and Wingless/Wnt-1 leads to the establishment of a Notch dependent organizer at the boundary. By means of a Systems Biology approach that combines mathematical modeling and both in silico and in vivo experiments in the Drosophila wing primordium, we modeled and tested this regulatory network and present evidence that a novel property, namely refractoriness to the Wingless signaling molecule, is required in boundary cells for the formation of a stable dorsal-ventral boundary. This new property has been validated in vivo, promotes mutually exclusive domains of Notch and Wingless activities and confers stability to the dorsal-ventral boundary. A robustness analysis of the regulatory network complements our results and ensures its biological plausibility.

Show MeSH