Drosophila Araucan and Caupolican Integrate Intrinsic and Signalling Inputs for the Acquisition by Muscle Progenitors of the Lateral Transverse Fate

Abstract

A central issue of myogenesis is the acquisition of identity by individual muscles. In Drosophila, at the time muscle progenitors are singled out, they already express unique combinations of muscle identity genes. This muscle code results from the integration of positional and temporal signalling inputs. Here we identify, by means of loss-of-function and ectopic expression approaches, the Iroquois Complex homeobox genes araucan and caupolican as novel muscle identity genes that confer lateral transverse muscle identity. The acquisition of this fate requires that Araucan/Caupolican repress other muscle identity genes such as slouch and vestigial. In addition, we show that Caupolican-dependent slouch expression depends on the activation state of the Ras/Mitogen Activated Protein Kinase cascade. This provides a comprehensive insight into the way Iroquois genes integrate in muscle progenitors, signalling inputs that modulate gene expression and protein activity.

Muscle Cell Fate Choice Requires the T-Box Transcription Factor Midline in Drosophila

“…Along with Mid, the Ara/Caup (Carrasco-Rando et al 2011), Ap (Bourgouin et al 1992), Msh (Nose et al 1998), Lms (Muller et al 2010), and Kr (Ruiz-Gomez et al 1997) transcription factors contribute to the development of LT3 and LT4. Ara/Caup is expressed in the progenitors for all four LTs, where it represses the VA1/2 fate and corresponding Slou expression in the LT3/4 progenitor (Carrasco-Rando et al 2011). These findings suggest that Ara/Caup acts at an early stage before the progenitor becomes fully committed to one developmental program.…”

“…At stage 10, we found that Mid was coexpressed with Kr in the LT3/4 progenitor and VA1/2 progenitor but not that of LT1/2 (Figure 2A). Kr continued to be detected in the FCs for LT1-4, VA1, and VA2 immediately after division and was detectable through stages 14 and 15 Beckett and Baylies 2007;Carrasco-Rando et al 2011), but declined in the LT1, LT3, and VA1 FCs by late stage 11 (Figure 2, B-D) Beckett and Baylies 2007;Carrasco-Rando et al 2011). Similarly, Mid was lost in the VA1 and LT3 FCs by stage 12 but, like Kr, was detectable in the FCs and the growing VA2 and LT4 muscles into stage 15 (Figure 2, E-G, Figure S2).…”

“…FCs dictate the number of cell fusion events that take place, leading to a characteristic number of nuclei for each muscle in the pattern . These fusing nuclei adopt the transcriptional profile of the original FC nucleus (Bourgouin et al 1992;D'Alessio and Frasch 1996;Ruiz-Gomez et al 1997;Jagla et al 1998;Keller et al 1998;Nose et al 1998;Crozatier and Vincent 1999;Knirr et al 1999;Duan et al 2007;Muller et al 2010;Carrasco-Rando et al 2011;Boukhatmi et al 2012;Schaub et al 2012), which determines the specific morphological features of each muscle fiber.The identity of each FC, and its capacity to confer this identify on the resulting muscle fiber, is determined by expression of a unique combination of transcription factors in FCs (Baylies et al 1998;Frasch 1999;Beckett and Baylies 2007;Tixier et al 2010). Correspondingly, the loss or misexpression of these identity transcription factors (iTFs) can affect the formation and morphology of the specific muscles in which they are expressed.…”

“…FCs dictate the number of cell fusion events that take place, leading to a characteristic number of nuclei for each muscle in the pattern . These fusing nuclei adopt the transcriptional profile of the original FC nucleus (Bourgouin et al 1992;D'Alessio and Frasch 1996;Ruiz-Gomez et al 1997;Jagla et al 1998;Keller et al 1998;Nose et al 1998;Crozatier and Vincent 1999;Knirr et al 1999;Duan et al 2007;Muller et al 2010;Carrasco-Rando et al 2011;Boukhatmi et al 2012;Schaub et al 2012), which determines the specific morphological features of each muscle fiber.…”

Expanding the Iroquois genes repertoire: a non-transcriptional function in cell cycle progression

“…Or, by controlling the expression of the slouch gene, Ara and Caup specify the lateral transverse muscle fate. 13 Iro genes contribute to territorial growth in the eye and wing imaginal discs by generating organizing borders at the Keywords: cell proliferation, Drosophila, imaginal discs, Iroquois genes, tumor suppressor genes List of abbreviations and acronyms: ara, araucan; CBD, Cyclin Binding Domain; Cdk2, Cyclin-dependent kinase 2; caup, caupolican; HD, homeodomain; Iro, Iroquois; Irx, Iroquois-related genes; mirr, mirror; TALE, Three Amino acid Loop Extension; TSG, Tumor Suppressor Genes confrontation of Iro-expressing and nonexpressing cells (the dorso/ventral and the notum/wing hinge organizers, respectively. [7][8][9]14 ) In addition, the observation that clones of iro mutant cells in the eye disc are larger than wild-type clones suggested that Iro proteins played a role in the control of cell proliferation.…”