Retrograde Bone Morphogenetic Protein Signaling Shapes a Key Circadian Pacemaker Circuit

Gorostiza, Ezequiel Axel; Ceriani, M. Fernanda

doi:10.1523/jneurosci.3448-12.2013

Cited by 18 publications

(25 citation statements)

References 64 publications

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“…Similar conclusions were reached by Depetris-Chauvin et al. [ 30 ] and Gorostiza and Ceriani [ 33 ]. Conversely, here we show that the PDF − CRY ∗ and the PDF − CRY − cells appear to be less sensitive to developmental effects ( Figures 5 C and 5D).…”

Section: Resultssupporting

confidence: 90%

The Logic of Circadian Organization in Drosophila

et al. 2014

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SummaryBackgroundIn the fruit fly Drosophila melanogaster, interlocked negative transcription/translation feedback loops provide the core of the circadian clock that generates rhythmic phenotypes. Although the current molecular model portrays the oscillator as cell autonomous, cross-talk among clock neurons is essential for robust cycling behavior. Nevertheless, the functional organization of the neuronal network remains obscure.ResultsHere we show that shortening or lengthening of the circadian period of locomotor activity can be obtained either by targeting different groups of clock cells with the same genetic manipulation or by challenging the same group of cells with activators and repressors of neuronal excitability.ConclusionsBased on these observations we interpret circadian rhythmicity as an emerging property of the circadian network and we propose an initial model for its architectural design.

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Section: Resultssupporting

confidence: 90%

The Logic of Circadian Organization in Drosophila

et al. 2014

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“…On the other hand, expression of a RNAi line directed to EcR in PDF neurons rescued the structural plasticity to wild type levels, antagonizing the effects caused by Mmp1 overexpression. Along these lines, downregulation of EcR affected PDF neurons per se , clamping the structure in the more complex, highly arborized, configuration ( Figure S3 B and [33] ).…”

Section: Resultsmentioning

confidence: 85%

Mmp1 Processing of the PDF Neuropeptide Regulates Circadian Structural Plasticity of Pacemaker Neurons

et al. 2014

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In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior.

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“…3 Together, these phenotypes all suggest that gbb has a broader and previously unrecognized role in the regulation of ecdysis in both larval and pupal development. Regulation of ecdysis by gbb could be related to its role in the regulation of energy homeostasis (65), which is intimately tied to the organism's ability to undergo or delay ecdysis (53), or to the role of gbb in circadian neural circuit development (66,67). With regard to the regulation of pupal ecdysis hormones, wit signaling is required specifically in CCAP neurons for CCAP expression (29).…”

Section: Functions Of Gbb In Regulation Of Ecdysis Hormonesmentioning

confidence: 99%

Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences

Anderson

Wharton

2017

Journal of Biological Chemistry

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The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles. They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer. Multiple proteolytic processing sites in Glass bottom boat (Gbb), the BMP7 ortholog, can produce distinct ligand forms. Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand. We hypothesized that the Gbb prodomain is involved not only in regulating the production of specific ligands but also their signaling output. We found that blocking NS cleavage increased association of the full-length prodomain with Gbb15, resulting in a concomitant decrease in signaling activity. Moreover, NS cleavage was required for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture. Gbb NS cleavage was also required for viability through its regulation of pupal ecdysis in a type II receptor Wishful thinking (Wit)-dependent manner. In fact, Gbb38-mediated signaling exhibits a preference for Wit over the other type II receptor Punt. Finally, we discovered that Gbb38 is produced when processing at the S1/S0 site is blocked by linked glycosylation in third instar larvae. Our findings demonstrate that BMP prodomain cleavage ensures that the mature ligand is not inhibited by the prodomain. Furthermore, alternative processing of BMP proproteins produces ligands that signal through different receptors and exhibit specific developmental functions.

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Retrograde Bone Morphogenetic Protein Signaling Shapes a Key Circadian Pacemaker Circuit

Cited by 18 publications

References 64 publications

The Logic of Circadian Organization in Drosophila

The Logic of Circadian Organization in Drosophila

Mmp1 Processing of the PDF Neuropeptide Regulates Circadian Structural Plasticity of Pacemaker Neurons

Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences

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