Heterodimerization-dependent secretion of bone morphogenetic proteins in Drosophila

Bauer, Max; Aguilar, Gustavo; Wharton, Kristi A.; Matsuda, Shinya; Affolter, Markus

doi:10.1016/j.devcel.2023.03.008

Cited by 14 publications

(19 citation statements)

References 63 publications

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“…Therefore, we decided to investigate the function of Gbb in GSC maintenance and differentiation. First to understand expression pattern of Dpp and Gbb, we conducted anti-HA staining of fully functional HA-tagged Dpp and Gbb ( 30, 31 ) to detect intracellular fraction of Dpp and Gbb. In a past report, Dpp was shown to be expressed both in hub cells and CySCs by RT-PCR ( 11 ).…”

Section: Resultsmentioning

confidence: 99%

“…Based on these results, we propose that both ligands, Dpp and Gbb, may have critical effect both on GSC maintenance and prevention of dedifferentiation. Despite Dpp shows uniform distribution over the entire tissue and Gbb has broad expression pattern, we observed co-localization of Dpp (mScarlet-Dpp) and Gbb (GFP-Gbb) predominantly within the hub, where they may contribute to the formation of sharply graded signaling outcomes in the cells around the niche (Figure 5L, M).” A recent report has demonstrated that the heterodimers of Dpp-Gbb form within a cell prior to secretion and that it triggers strong signaling ( 31 ). It is possible that Dpp/Gbb heterodimer may form specifically in the hub and contribute to graded response of cells.…”

Section: Resultsmentioning

confidence: 99%

“…Our study suggests a requirement of both Dpp and Gbb for observed cellular responses, and co-localization of Dpp-Gbb was exclusively seen in the hub (Figure 5L, M), suggesting a possibility that Dpp-Gbb may form heterodimer and distribution of which might be tightly restricted around the hub even though each ligand alone can diffuse freely. A recent report has demonstrated that the heterodimers of Dpp-Gbb preferentially produced in Dpp producing cells and play critical roles during development ( 31, 51 ). This may contribute to the formation of sharply graded signaling outcomes around the niche.…”

Section: Discussionmentioning

confidence: 99%

“…yw (BDSC189) was used for wildtype. UAS-GFP-Mad ( 50 ) , HA-dpp ( 30 ) , UAS-HA-trap ( 30 ) , HA-gbb ( 31 ) dppGal4 ( 30 ) lines are described elsewhere. FasIIIGal4 was obtained from DGRC, Kyoto Stock Center (A04-1-1 DGRC#103-948).…”

Section: Methodsmentioning

confidence: 99%

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Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation

Ridwan

Twille

Matsuda

et al. 2022

Preprint

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Drosophila male germline stem cells (GSCs) reside at the tip of the testis and surround a cluster of niche cells, called the hub. It has been believed that the Decapentaplegic (Dpp) ligand, secreted from the hub, only activates stem cells in close proximity, but not differentiating cells spaced one-cell layer away. However the range of Dpp diffusion is unknown. Here, using genetically encoded nanobodies, called Morphotrap, we physically block Dpp diffusion outside of the niche without interfering with niche-stem cell signaling. Surprisingly, we found that Dpp has an opposite effect on GSCs and on their immediate progenies, such that it promotes self-renewal of GSCs, while ensuring the differentiation of their daughter cells. When the signal from the diffusing fraction of Dpp was specifically blocked, differentiating daughter cells frequently dedifferentiated, suggesting that Dpp ensures asymmetric outcome of stem cells both inside and outside of the niche. We further show that these distinct signaling outcomes are achieved by the same canonical BMP pathway, through the typeI receptor, Thickveins (Tkv), and the downstream effector, Mothers against Dpp (Mad). Given the broad requirement of BMP pathway in many stem cell systems, we propose that such a self-contained behavior of a stem cell ligand may be a common mechanism to ensure special restriction of stem-cell niche.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation

Ridwan

Twille

Matsuda

et al. 2022

Preprint

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“…[81] Manipulating morphogen spreading also revealed previously unappreciated roles of morphogen dispersal. By applying HA trap to study Gbb (Glass bottom boat), another BMP type ligand, it has recently been shown that the active BMP-type ligands in the wing imaginal disc are heterodimers of Dpp and Gbb [82] as previously shown in the case of the formation of the posterior crossvein in the pupal wing. [83] While nichederived Dpp was thought to act in a short-range manner to maintain male germline stem cells (GSCs) in Drosophila, blocking endogenous Dpp spreading revealed an unexpected role of a diffusive fraction of Dpp in differentiating cells further away from the source.…”

Section: Biological and Experimental Relevance For Other Morphogen Sy...mentioning

confidence: 90%

Is Drosophila Dpp/BMP morphogen spreading required for wing patterning and growth?

Matsuda

Affolter

2023

BioEssays

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Secreted signaling molecules act as morphogens to control patterning and growth in many developing tissues. Since locally produced morphogens spread to form a concentration gradient in the surrounding tissue, spreading is generally thought to be the key step in the non‐autonomous actions. Here, we review recent advances in tool development to investigate morphogen function using the role of decapentaplegic (Dpp)/bone morphogenetic protein (BMP)‐type ligand in the Drosophila wing disc as an example. By applying protein binder tools to distinguish between the roles of Dpp spreading and local Dpp signaling, we found that Dpp signaling in the source cells is important for wing patterning and growth but Dpp spreading from this source cells is not as strictly required as previously thought. Given recent studies showing unexpected requirements of long‐range action of different morphogens, manipulating endogenous morphogen gradients by synthetic protein binder tools could shed more light on how morphogens act in developing tissues.

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The beauty of seeing the real thing: BMP heterodimer detection in vivo reveals dimer composition and activity

Collu¹,

Mlodzik²

2023

Developmental Cell

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Heterodimerization-dependent secretion of bone morphogenetic proteins in Drosophila

Cited by 14 publications

References 63 publications

Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation

Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation

Is Drosophila Dpp/BMP morphogen spreading required for wing patterning and growth?

The beauty of seeing the real thing: BMP heterodimer detection in vivo reveals dimer composition and activity

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