The Drosophila Hox Gene Deformed Sculpts Head Morphology via Direct Regulation of the Apoptosis Activator reaper

Lohmann, Ingrid; McGinnis, Nadine; Bodmer, Morana; McGinnis, William

doi:10.1016/s0092-8674(02)00871-1

Cited by 196 publications

(180 citation statements)

References 57 publications

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“…Our data show a clear increase in spiracle-associated cell death in A7 of both sexes. It has been reported that posterior embryonic apoptosis is positively regulated by Abd-B directly through activation of the proapoptotic gene reaper (42). If similar Abd-B-mediated regulation of apoptosis occurs during pupal development, there must be additional regional controls that restrict these events to those cells surrounding the developing spiracles.…”

Section: Discussionmentioning

confidence: 99%

Sexually dimorphic regulation of the Wingless morphogen controls sex-specific segment number in Drosophila

Wang

Kidd

Carroll

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Sexual dimorphism is widespread throughout the metazoa and plays important roles in mate recognition and preference, sexbased niche partitioning, and sex-specific coadaptation. One notable example of sex-specific differences in insect body morphology is presented by the higher diptera, such as Drosophila, in which males develop fewer abdominal segments than females. Because diversity in segment number is a distinguishing feature of major arthropod clades, it is of fundamental interest to understand how different numbers of segments can be generated within the same species. Here we show that sex-specific and segment-specific regulation of the Wingless (Wg) morphogen underlies the development of sexually dimorphic adult segment number in Drosophila. Wg expression is repressed in the developing terminal male abdominal segment by the combination of the Hox protein Abdominal-B (Abd-B) and the sex-determination regulator Doublesex (Dsx). The subsequent loss of the terminal male abdominal segment during pupation occurs through a combination of developmental processes including segment compartmental transformation, apoptosis, and suppression of cell proliferation. Furthermore, we show that ectopic expression of Wg is sufficient to rescue this loss. We propose that dimorphic Wg regulation, in concert with monomorphic segment-specific programmed cell death, are the principal mechanisms of sculpting the sexually dimorphic abdomen of Drosophila.morphogenesis | segmentation | homeotic | epithelia B rachycera, higher diptera that include drosophilidae, exhibit an evolutionary trend toward reduced abdominal size that contributes to swift, maneuverable flight (1). Such reduction is especially pronounced within the infraorder Muscomorpha. Within this group of flies, abdominal reduction is sexually dimorphic such that adult males have fewer segments than females. Lower diptera, which includes mosquitoes and midges, retain ancestral morphology with respect to segment number; both adult males and females generate eight abdominal segments. In Muscomorpha the most posterior adult abdominal segments (all or a subset of segments A5-A8) are modified in females, usually as a telescoping ovipositor, whereas corresponding segments are absent in males (2). In all diptera, segment number is monomorphic during embryogenesis and larval development, reflecting the basal insect body plan of three head, three thoracic, and 11 abdominal segments. For most diptera, only embryonic abdominal segments 1-8 generate adult abdominal tissue (only segments 1-7 in the drosophilidae). The more posterior embryonic segments contribute to the adult genitalia. During pupation, sex-specific developmental programs are deployed that sculpt sexually dimorphic segment morphology and number.The posterior abdomen of Drosophila melanogaster serves as an excellent model to study the development of these sex-specific morphologies. Posterior abdominal segment identity, morphology, and number in both sexes is regulated by the Hox protein Abdominal-B (Abd-B) (3, 4). Abd-B ex...

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Section: Discussionmentioning

confidence: 99%

Sexually dimorphic regulation of the Wingless morphogen controls sex-specific segment number in Drosophila

Wang

Kidd

Carroll

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…21,22 Although these results could be interpreted to indicate that IAPs do not play a major role for caspase regulation in mammals, a more likely alternative is that their physiological role is masked by functional redundancy. If relatively short-lived organisms such as fruit flies protect themselves against unwanted death using multiple caspase inhibitors (see below; Figure 1), 6,[8][9][10][11][12][13][14][15][23][24][25][26][27][28][29][30][31][32][33][34][35] it would come as a great surprise if mammals would employ fewer safeguards to control caspase activity.…”

Section: Brakes On Death: Caspase Inhibition By Inhibitor Of Apoptosimentioning

confidence: 99%

“…38 The reaper gene, and to some extent grim, hid and sickle, are transcriptionally activated in response to many different proapoptotic signals, including steroid hormones, a variety of developmental signals, radiation and various forms of cellular stress or injury. [24][25][26]36,[39][40][41] These genes share a very large, complex regulatory region containing numerous enhancer (and silencer) elements that are the target for many different transcriptional regulators. Therefore, one major mechanism by which different signaling pathways converge in Drosophila is through transcriptional activation of reaper, hid and grim.…”

Section: Relieving the Brakes: Induction Of Apoptosis By Reaper-familmentioning

confidence: 99%

Regulation of apoptosis in Drosophila

2008

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Insects have made major contributions to understanding the regulation of cell death, dating back to the pioneering work of Lockshin and Williams on death of muscle cells during postembryonic development of Manduca. A physically smaller cousin of moths, the fruit fly Drosophila melanogaster, offers unique advantages for studying the regulation of cell death in response to different apoptotic stimuli in situ. Different signaling pathways converge in Drosophila to activate a common death program through transcriptional activation of reaper, hid and grim. Reaper-family proteins induce apoptosis by binding to and antagonizing inhibitor of apoptosis proteins (IAPs), which in turn inhibit caspases. This switch from life to death relies extensively on targeted degradation of cell death proteins by the ubiquitin-proteasome pathway. Drosophila IAP-1 (Diap1) functions as an E3-ubiquitin ligase to protect cells from unwanted death by promoting the degradation of the initiator caspase Dronc. However, in response to apoptotic signals, Reaper-family proteins are produced, which promote the auto-ubiquitination and degradation of Diap1, thereby removing the 'brakes on death' in cells that are doomed to die. More recently, several other ubiquitin pathway proteins were found to play important roles for caspase regulation, indicating that the control of cell survival and death relies extensively on targeted degradation by the ubiquitin-proteasome pathway.

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“…It is still not fully understood how developmental pathways integrate both differentiation and apoptosis in tissues. The identification of developmental factors, such as Deformed, Abdominal B, which regulate RHG gene transcription [17], was a step towards the identification of rpr transcriptional regulators but a thorough analysis of findings is needed to fully understand the transcriptional regulation of RHG genes. Recently, Zhou and colleagues showed that epigenetic regulations play an active part in the coordinated expression of rpr and hid during apoptosis in embryos, suggesting that a complete understanding of RHG regulation may lie in alternative approaches [18].…”

Section: Apoptosis During Embryogenesismentioning

confidence: 99%

Cell death: what can we learn from flies? Editorial for the special review issue on Drosophila apoptosis

Mollereau

2009

Apoptosis

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The Drosophila Hox Gene Deformed Sculpts Head Morphology via Direct Regulation of the Apoptosis Activator reaper

Cited by 196 publications

References 57 publications

Sexually dimorphic regulation of the Wingless morphogen controls sex-specific segment number in Drosophila

Sexually dimorphic regulation of the Wingless morphogen controls sex-specific segment number in Drosophila

Regulation of apoptosis in Drosophila

Cell death: what can we learn from flies? Editorial for the special review issue on Drosophila apoptosis

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