scholarly journals Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sabine Schürmann ◽  
Georg Steffes ◽  
Dominique Manikowski ◽  
Philipp Kastl ◽  
Ursula Malkus ◽  
...  
Keyword(s):  
Cell Fate ◽  
Proteolytic Processing ◽  
Wing Development ◽  
Cell Fate Determination ◽  
Site Specific ◽  
Drosophila Wing ◽  
Direct Patterning ◽  
Processing Site ◽  
Membrane Bound ◽  
Morphogen Transport

Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells. While several proposed Hh transport modes tie directly into these unusual properties, the crucial step of Hh relay from producing cells to receptors on remote responding cells remains unresolved. Using wing development in Drosophila melanogaster as a model, we show that Hh relay and direct patterning of the 3–4 intervein region strictly depend on proteolytic removal of lipidated N-terminal membrane anchors. Site-directed modification of the N-terminal Hh processing site selectively eliminated the entire 3–4 intervein region, and additional targeted removal of N-palmitate restored its formation. Hence, palmitoylated membrane anchors restrict morphogen spread until site-specific processing switches membrane-bound Hh into bioactive forms with specific patterning functions.

Lhx2, a vertebrate homologue of apterous, regulates vertebrate limb outgrowth

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 3925-3934 ◽  
Author(s):  
C. Rodriguez-Esteban ◽  
J.W. Schwabe ◽  
J.D. Pena ◽  
D.E. Rincon-Limas ◽  
J. Magallon ◽  
...  
Keyword(s):  
Cell Fate ◽  
Wing Development ◽  
Dorsoventral Axis ◽  
Drosophila Wing ◽  
Vertebrate Limb ◽  
Limb Outgrowth ◽  
Necessary And Sufficient ◽  
Dorsal Cell Fate

apterous specifies dorsal cell fate and directs outgrowth of the wing during Drosophila wing development. Here we show that, in vertebrates, these functions appear to be performed by two separate proteins. Lmx-1 is necessary and sufficient to specify dorsal identity and Lhx2 regulates limb outgrowth. Our results suggest that Lhx2 is closer to apterous than Lmx-1, yet, in vertebrates, Lhx2 does not specify dorsal cell fate. This implies that in vertebrates, unlike Drosophila, limb outgrowth can be dissociated from the establishment of the dorsoventral axis.

scholarly journals In-phase oscillation of global regulons is orchestrated by a pole-specific organizer

2016 ◽  
Vol 113 (44) ◽  
pp. 12550-12555 ◽  
Author(s):  
Balaganesh Janakiraman ◽  
Johann Mignolet ◽  
Sharath Narayanan ◽  
Patrick H. Viollier ◽  
Sunish Kumar Radhakrishnan
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Caulobacter Crescentus ◽  
Transcriptional Regulators ◽  
Forward Genetics ◽  
Cell Fate Determination ◽  
Global Regulator ◽  
Site Specific ◽  
Phase Oscillation ◽  
A Site

Cell fate determination in the asymmetric bacteriumCaulobacter crescentus(Caulobacter) is triggered by the localization of the developmental regulator SpmX to the old (stalked) cell pole during the G1→S transition. Although SpmX is required to localize and activate the cell fate-determining kinase DivJ at the stalked pole inCaulobacter, in cousins such asAsticcacaulis, SpmX directs organelle (stalk) positioning and possibly other functions. We define the conserved σ54-dependent transcriptional activator TacA as a global regulator inCaulobacterwhose activation by phosphorylation is indirectly down-regulated by SpmX. Using a combination of forward genetics and cytological screening, we uncover a previously uncharacterized and polarized component (SpmY) of the TacA phosphorylation control system, and we show that SpmY function and localization are conserved. Thus, SpmX organizes a site-specific, ancestral, and multifunctional regulatory hub integrating the in-phase oscillation of two global transcriptional regulators, CtrA (the master cell cycle transcriptional regulator A) and TacA, that perform important cell cycle functions.

scholarly journals Complex Proteolytic Processing Acts on Delta, a Transmembrane Ligand for Notch, during Drosophila Development

1998 ◽  
Vol 9 (7) ◽  
pp. 1709-1723 ◽  
Author(s):  
Kristin M. Klueg ◽  
Todd R. Parody ◽  
Marc A.T. Muskavitch
Keyword(s):  
Cell Fate ◽  
Cultured Cells ◽  
Cellular Responses ◽  
Proteolytic Processing ◽  
Cell Fate Specification ◽  
A Cell ◽  
Membrane Bound ◽  
Delta Functions ◽  
Intracellular Domains

Delta functions as a cell nonautonomous membrane-bound ligand that binds to Notch, a cell-autonomous receptor, during cell fate specification. Interaction between Delta and Notch leads to signal transduction and elicitation of cellular responses. During our investigations to further understand the biochemical mechanism by which Delta signaling is regulated, we have identified four Delta isoforms inDrosophila embryonic and larval extracts. We have demonstrated that at least one of the smaller isoforms, Delta S, results from proteolysis. Using antibodies to the Delta extracellular and intracellular domains in colocalization experiments, we have found that at least three Delta isoforms exist in vivo, providing the first evidence that multiple forms of Delta exist during development. Finally, we demonstrate that Delta is a transmembrane ligand that can be taken up by Notch-expressing Drosophila cultured cells. Cell culture experiments imply that full-length Delta is taken up by Notch-expressing cells. We present evidence that suggests this uptake occurs by a nonphagocytic mechanism.

scholarly journals msh specifies dorsal cell fate in the Drosophila wing

Development ◽  
2001 ◽  
Vol 128 (17) ◽  
pp. 3263-3268 ◽  
Author(s):  
Marco Milán ◽  
Ulrich Weihe ◽  
Stanley Tiong ◽  
Welcome Bender ◽  
Stephen M. Cohen
Keyword(s):  
Cell Fate ◽  
Imaginal Disc ◽  
Homeobox Gene ◽  
Wing Imaginal Disc ◽  
Wing Development ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Signaling Center ◽  
Dorsal Cells ◽  
Dorsal Cell Fate

Drosophila limbs develop from imaginal discs that are subdivided into compartments. Dorsal-ventral subdivision of the wing imaginal disc depends on apterous activity in dorsal cells. Apterous protein is expressed in dorsal cells and is responsible for (1) induction of a signaling center along the dorsal-ventral compartment boundary (2) establishment of a lineage restriction boundary between compartments and (3) specification of dorsal cell fate. Here, we report that the homeobox gene msh (muscle segment homeobox) acts downstream of apterous to confer dorsal identity in wing development.

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