delilah, prospero and D-Pax2 constitute a gene regulatory network essential for the development of functional proprioceptors

In this work we describe a gene regulatory network consisting of three transcription factors- Prospero (Pros), D-Pax2/Shaven (Sv) and Delilah/Taxi (Dei/Tx)- that dictates two alternative differentiation programs within the proprioceptive lineage in Drosophila. D-Pax2 and Pros control the differentiation of cap versus scolopale cells in the chordotonal organ lineage by, respectively, activating and repressing the transcription of dei. Normally, D-Pax2 activates the expression of dei in the cap cell but is unable to do so in the scolopale cell where Pros is co-expressed. If D-Pax2 activity is lost, the cap cell fails to express dei as well as additional proteins, such as αTub85E, that characterize a fully differentiated cap cell. In contrast, if Pros activity is lost, dei is ectopically expressed in the scolopale cell that, as a consequence, adopts some cap cell features, including the expression of αTub85E. We further show that D-Pax2 and Pros exert their effects on dei transcription via a 262 bp chordotonal-specific regulatory module (deiChO-262) in which two D-Pax2- and three Pros-binding sites were identified experimentally. When this regulatory element was removed from the fly genome, the cap- and ligament-specific expression of dei was lost. Ectopic expression of D-Pax2, or the elimination of pros activity, did not lead to upregulation of dei in the scolopale cell in the absence of the D-Pax2-responsive deiChO-262 enhancer. Finally, we show that the regulation of dei expression via the D-Pax2/Pros-responsive element is critical for chordotonal organ functionality and coordinated larval locomotion.

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Delilah, prospero, and D-Pax2 constitute a gene regulatory network essential for the development of functional proprioceptors

eLife ◽

10.7554/elife.70833 ◽

2021 ◽

Vol 10 ◽

Author(s):

Adel Avetisyan ◽

Yael Glatt ◽

Maya Cohen ◽

Yael Timerman ◽

Nitay Aspis ◽

...

Keyword(s):

Gene Regulatory Network ◽

Cell Fate ◽

Binding Sites ◽

Regulatory Network ◽

Genetic Networks ◽

Chordotonal Organ ◽

Cell Fate Determination ◽

Specific Expression ◽

Gene Regulatory ◽

Do So

Coordinated animal locomotion depends on the development of functional proprioceptors. While early cell-fate determination processes are well characterized, little is known about the terminal differentiation of cells within the proprioceptive lineage and the genetic networks that control them. In this work we describe a gene regulatory network consisting of three transcription factors–Prospero (Pros), D-Pax2, and Delilah (Dei)–that dictates two alternative differentiation programs within the proprioceptive lineage in Drosophila. We show that D-Pax2 and Pros control the differentiation of cap versus scolopale cells in the chordotonal organ lineage by, respectively, activating and repressing the transcription of dei. Normally, D-Pax2 activates the expression of dei in the cap cell but is unable to do so in the scolopale cell where Pros is co-expressed. We further show that D-Pax2 and Pros exert their effects on dei transcription via a 262 bp chordotonal-specific enhancer in which two D-Pax2- and three Pros-binding sites were identified experimentally. When this enhancer was removed from the fly genome, the cap- and ligament-specific expression of dei was lost, resulting in loss of chordotonal organ functionality and defective larval locomotion. Thus, coordinated larval locomotion depends on the activity of a dei enhancer that integrates both activating and repressive inputs for the generation of a functional proprioceptive organ.

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Early asymmetric cues triggering the dorsal/ventral gene regulatory network of the sea urchin embryo

eLife ◽

10.7554/elife.04664 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 22

Author(s):

Vincenzo Cavalieri ◽

Giovanni Spinelli

Keyword(s):

Gene Regulatory Network ◽

Sea Urchin ◽

Regulatory Network ◽

Ectopic Expression ◽

Paracentrotus Lividus ◽

Loss Of Function ◽

Mapk Activity ◽

Sea Urchin Embryo ◽

Gene Regulatory ◽

Dorsal Cells

Dorsal/ventral (DV) patterning of the sea urchin embryo relies on a ventrally-localized organizer expressing Nodal, a pivotal regulator of the DV gene regulatory network. However, the inceptive mechanisms imposing the symmetry-breaking are incompletely understood. In Paracentrotus lividus, the Hbox12 homeodomain-containing repressor is expressed by prospective dorsal cells, spatially facing and preceding the onset of nodal transcription. We report that Hbox12 misexpression provokes DV abnormalities, attenuating nodal and nodal-dependent transcription. Reciprocally, impairing hbox12 function disrupts DV polarity by allowing ectopic expression of nodal. Clonal loss-of-function, inflicted by blastomere transplantation or gene-transfer assays, highlights that DV polarization requires Hbox12 action in dorsal cells. Remarkably, the localized knock-down of nodal restores DV polarity of embryos lacking hbox12 function. Finally, we show that hbox12 is a dorsal-specific negative modulator of the p38-MAPK activity, which is required for nodal expression. Altogether, our results suggest that Hbox12 function is essential for proper positioning of the DV organizer.

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Cis-regulatory evolution integrated the Bric-à-brac transcription factors into a novel fruit fly gene regulatory network

eLife ◽

10.7554/elife.32273 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 13

Author(s):

Maxwell J Roeske ◽

Eric M Camino ◽

Sumant Grover ◽

Mark Rebeiz ◽

Thomas Michael Williams

Keyword(s):

Transcription Factors ◽

Gene Regulatory Network ◽

Regulatory Network ◽

Morphological Evolution ◽

Regulatory Element ◽

Fruit Fly ◽

Evolutionary Changes ◽

Protein Dna Interactions ◽

Expression Evolution ◽

Gene Regulatory

Gene expression evolution through gene regulatory network (GRN) changes has gained appreciation as a driver of morphological evolution. However, understanding how GRNs evolve is hampered by finding relevant cis-regulatory element (CRE) mutations, and interpreting the protein-DNA interactions they alter. We investigated evolutionary changes in the duplicated Bric-à-brac (Bab) transcription factors and a key Bab target gene in a GRN underlying the novel dimorphic pigmentation of D. melanogaster and its relatives. It has remained uncertain how Bab was integrated within the pigmentation GRN. Here, we show that the ancestral transcription factor activity of Bab gained a role in sculpting sex-specific pigmentation through the evolution of binding sites in a CRE of the pigment-promoting yellow gene. This work demonstrates how a new trait can evolve by incorporating existing transcription factors into a GRN through CRE evolution, an evolutionary path likely to predominate newly evolved functions of transcription factors.

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An otx cis -regulatory module: a key node in the sea urchin endomesoderm gene regulatory network

Developmental Biology ◽

10.1016/j.ydbio.2004.02.025 ◽

2004 ◽

Vol 269 (2) ◽

pp. 536-551 ◽

Cited By ~ 53

Author(s):

Chiou-Hwa Yuh ◽

Elizabeth R Dorman ◽

Meredith L Howard ◽

Eric H Davidson

Keyword(s):

Gene Regulatory Network ◽

Sea Urchin ◽

Regulatory Network ◽

Regulatory Module ◽

Gene Regulatory

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Cis-regulatory evolution integrated the Bric-à-brac transcription factors into a novel fruit fly gene regulatory network

10.1101/200360 ◽

2017 ◽

Author(s):

Maxwell J. Roeske ◽

Eric M. Camino ◽

Sumant Grover ◽

Mark Rebeiz ◽

Thomas M. Williams

Keyword(s):

Transcription Factors ◽

Gene Regulatory Network ◽

Regulatory Network ◽

Morphological Evolution ◽

Regulatory Element ◽

Fruit Fly ◽

Protein Coding ◽

Evolutionary Changes ◽

Expression Evolution ◽

Gene Regulatory

AbstractGene expression evolution through gene regulatory network (GRN) changes has gained appreciation as a driver of morphological evolution. However, understanding how GRNs evolve is hampered by finding relevant cis-regulatory element (CRE) mutations, and interpreting the protein-DNA interactions they alter. We investigated evolutionary changes in the duplicated Bric-à-brac (Bab) transcription factors and a key Bab target gene in a GRN underlying the novel dimorphic pigmentation of D. melanogaster and its relatives. It has remained uncertain how Bab was integrated within the pigmentation GRN. Here we show that Bab gained a role in sculpting sex-specific pigmentation through the evolution of binding sites in a CRE of the pigment-promoting yellow gene and without any noteworthy changes to Bab protein coding sequences. This work demonstrates how a new trait can evolve by incorporating existing transcription factors into a GRN through CRE evolution, an evolutionary path likely to predominate newly evolved functions of transcription factors.

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