Development最新文献_第4页

Temporal dynamics of BMP/Nodal ratio drive tissue-specific gastrulation morphogenesis.

IF 3.7 2区生物学

Development Pub Date : 2024-12-09 DOI: 10.1242/dev.202931

Alyssa A Emig, Megan Hansen, Sandra Grimm, Cristian Coarfa, Nathan D Lord, Margot Kossmann Williams

引用次数: 0

Versican controlled by Lmx1b regulates hyaluronate density and hydration for semicircular canal morphogenesis. 由 Lmx1b 控制的 Versican 可调节透明质酸密度和水合作用，促进半规管形态发生。

IF 3.7 2区生物学

Development Pub Date : 2024-12-09 DOI: 10.1242/dev.203003

Yusuke Mori, Sierra Smith, Jiacheng Wang, Nadia Eliora, Kira L Heikes, Akankshi Munjal

{"title":"Versican controlled by Lmx1b regulates hyaluronate density and hydration for semicircular canal morphogenesis.","authors":"Yusuke Mori, Sierra Smith, Jiacheng Wang, Nadia Eliora, Kira L Heikes, Akankshi Munjal","doi":"10.1242/dev.203003","DOIUrl":"10.1242/dev.203003","url":null,"abstract":"During inner ear semicircular canal morphogenesis in zebrafish, patterned canal-genesis zones express genes for extracellular matrix component synthesis. These include hyaluronan and the hyaluronan-binding chondroitin sulfate proteoglycan Versican, which are abundant in the matrices of many developing organs. Charged hyaluronate polymers play a key role in canal morphogenesis through osmotic swelling. However, the developmental factor(s) that pattern the synthesis of the matrix components and regulation of hyaluronate density and swelling are unknown. Here, we identify the transcription factor, Lmx1b, as a positive transcriptional regulator of hyaluronan, Versican, and chondroitin synthesis genes crucial for canal morphogenesis. We show that Versican regulates hyaluronan density through its protein core, whereas the charged chondroitin side chains contribute to the hydration of hyaluronate-ECM. Versican-tuned properties of hyaluronate matrices may be a broadly used mechanism in morphogenesis with important implications for understanding diseases where these matrices are impaired, and for hydrogel engineering for tissue regeneration.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fate specification triggers a positive feedback loop of TEAD-YAP and NANOG to promote epiblast formation in preimplantation embryos.

IF 3.7 2区生物学

Development Pub Date : 2024-12-04 DOI: 10.1242/dev.203091

Naoki Hirono, Masakazu Hashimoto, Hiromi Shimojo, Hiroshi Sasaki

{"title":"Fate specification triggers a positive feedback loop of TEAD-YAP and NANOG to promote epiblast formation in preimplantation embryos.","authors":"Naoki Hirono, Masakazu Hashimoto, Hiromi Shimojo, Hiroshi Sasaki","doi":"10.1242/dev.203091","DOIUrl":"https://doi.org/10.1242/dev.203091","url":null,"abstract":"In preimplantation embryos, epiblast (EPI) fate specification from the inner cell mass is controlled by the segregation of NANOG and GATA6 expression. TEAD-YAP interaction is activated during EPI formation, and is required for pluripotency factor expression. These events occur asynchronously with similar timing during EPI formation, and their relationship remains elusive. Here, we examined the relationship between NANOG-GATA6 and TEAD-YAP. The nuclear accumulation of YAP takes place only in EPI-specified cells, and a positive feedback loop operates between NANOG and TEAD-YAP. The effects of TEAD-YAP on SOX2 upregulation in EPI-specified cells are likely indirect. EPI fate specification also alters the response of Nanog, Sox2 and Cdx2 to TEAD-YAP. These results suggest that EPI-fate specification alters the transcriptional network from the morula-like to the EPI-specified state and activates TEAD-YAP to trigger a positive feedback loop with NANOG, which stabilizes the EPI fate. The coordinated occurrence of these processes in individual cells likely supports proper EPI formation under the condition of asynchronous EPI-fate specification.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Maintenance of niche architecture requires actomyosin and enables proper stem cell signaling and oriented division in the Drosophila testis.

IF 3.7 2区生物学

Development Pub Date : 2024-12-02 DOI: 10.1242/dev.204498

Gabriela S Vida, Elizabeth Botto, Stephen DiNardo

{"title":"Maintenance of niche architecture requires actomyosin and enables proper stem cell signaling and oriented division in the Drosophila testis.","authors":"Gabriela S Vida, Elizabeth Botto, Stephen DiNardo","doi":"10.1242/dev.204498","DOIUrl":"10.1242/dev.204498","url":null,"abstract":"Stem cells are critical to repair and regenerate tissues, and often reside in a niche that controls their behavior. Here we use the Drosophila testis niche, a paradigm for niche-stem cell interactions, to address the cell biological features that maintain niche structure and function during its steady-state operation. We report enrichment of the Myosin II (MyoII) and a key regulator of acto-myosin contractility (AMC), Rho Kinase (ROK), within the niche cell cortex at the interface with germline stem cells (GSCs). Compromising MyoII and ROK disrupts niche architecture, suggesting that AMC in niche cells is important to maintain its reproducible structure. Furthermore, defects in niche architecture disrupt GSC function. Our data suggest that the niche signals less robustly to adjacent germ cells yet permits increased numbers of cells to respond to the signal. Finally, compromising MyoII in niche cells leads to increased mis-orientation of centrosomes in GSCs as well as defects in the centrosome orientation checkpoint. Ultimately, this work identifies a critical role for AMC-dependent maintenance of niche structure to ensure a proper complement of stem cells that correctly execute divisions.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MRCK-1 activates non-muscle myosin for outgrowth of a unicellular tube in Caenorhabditis elegans. MRCK-1 激活非肌肉肌球蛋白，促进秀丽隐杆线虫单细胞管的生长。

IF 3.7 2区生物学

Development Pub Date : 2024-12-01 Epub Date: 2024-11-29 DOI: 10.1242/dev.202772

Evelyn M Popiel, Rhea Ahluwalia, Stefan Schuetz, Bin Yu, W Brent Derry

{"title":"MRCK-1 activates non-muscle myosin for outgrowth of a unicellular tube in Caenorhabditis elegans.","authors":"Evelyn M Popiel, Rhea Ahluwalia, Stefan Schuetz, Bin Yu, W Brent Derry","doi":"10.1242/dev.202772","DOIUrl":"10.1242/dev.202772","url":null,"abstract":"The formation and patterning of unicellular biological tubes is essential for metazoan development. It is well established that vascular tubes and neurons use similar guidance cues to direct their development, but the downstream mechanisms that promote the outgrowth of biological tubes are not well characterized. We show that the conserved kinase MRCK-1 and its substrate the regulatory light chain of non-muscle myosin, MLC-4, are required for outgrowth of the unicellular excretory canal in C. elegans. Ablation of MRCK-1 or MLC-4 in the canal causes severe truncations with unlumenized projections of the basal membrane. Structure-function analysis of MRCK-1 indicates that the kinase domain, but not the small GTPase-binding CRIB domain, is required for canal outgrowth. Expression of a phosphomimetic form of MLC-4 rescues canal truncations in mrck-1 mutants and shows enrichment at the growing canal tip. Moreover, our work reveals a previously unreported function for non-muscle myosin downstream of MRCK-1 in excretory canal outgrowth that may be conserved in the development of seamless tubes in other organisms.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

flt1 inactivation promotes zebrafish cardiac regeneration by enhancing endothelial activity and limiting the fibrotic response.

IF 3.7 2区生物学

Development Pub Date : 2024-12-01 Epub Date: 2024-11-29 DOI: 10.1242/dev.203028

Zhen-Yu Wang, Armaan Mehra, Qian-Chen Wang, Savita Gupta, Agatha Ribeiro da Silva, Thomas Juan, Stefan Günther, Mario Looso, Jan Detleffsen, Didier Y R Stainier, Rubén Marín-Juez

{"title":"flt1 inactivation promotes zebrafish cardiac regeneration by enhancing endothelial activity and limiting the fibrotic response.","authors":"Zhen-Yu Wang, Armaan Mehra, Qian-Chen Wang, Savita Gupta, Agatha Ribeiro da Silva, Thomas Juan, Stefan Günther, Mario Looso, Jan Detleffsen, Didier Y R Stainier, Rubén Marín-Juez","doi":"10.1242/dev.203028","DOIUrl":"10.1242/dev.203028","url":null,"abstract":"VEGFA administration has been explored as a pro-angiogenic therapy for cardiovascular diseases including heart failure for several years, but with little success. Here, we investigate a different approach to augment VEGFA bioavailability: by deleting the VEGFA decoy receptor VEGFR1 (also known as FLT1), one can achieve more physiological VEGFA concentrations. We find that after cryoinjury, zebrafish flt1 mutant hearts display enhanced coronary revascularization and endocardial expansion, increased cardiomyocyte dedifferentiation and proliferation, and decreased scarring. Suppressing Vegfa signaling in flt1 mutants abrogates these beneficial effects of flt1 deletion. Transcriptomic analyses of cryoinjured flt1 mutant hearts reveal enhanced endothelial MAPK/ERK signaling and downregulation of the transcription factor gene egr3. Using newly generated genetic tools, we observe egr3 upregulation in the regenerating endocardium, and find that Egr3 promotes myofibroblast differentiation. These data indicate that with enhanced Vegfa bioavailability, the endocardium limits myofibroblast differentiation via egr3 downregulation, thereby providing a more permissive microenvironment for cardiomyocyte replenishment after injury.","PeriodicalId":11375,"journal":{"name":"Development","volume":"151 23","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular characterization and sub-retinal transplantation of hypoimmunogenic human retinal sheets in a minipig model of severe photoreceptor degeneration.

IF 3.7 2区生物学

Development Pub Date : 2024-12-01 Epub Date: 2024-12-05 DOI: 10.1242/dev.203071

Andrea Barabino, Katia Mellal, Rimi Hamam, Anna Polosa, May Griffith, Jean-François Bouchard, Ananda Kalevar, Roy Hanna, Gilbert Bernier

{"title":"Molecular characterization and sub-retinal transplantation of hypoimmunogenic human retinal sheets in a minipig model of severe photoreceptor degeneration.","authors":"Andrea Barabino, Katia Mellal, Rimi Hamam, Anna Polosa, May Griffith, Jean-François Bouchard, Ananda Kalevar, Roy Hanna, Gilbert Bernier","doi":"10.1242/dev.203071","DOIUrl":"https://doi.org/10.1242/dev.203071","url":null,"abstract":"Retinal degenerative diseases affect millions of people worldwide, and legal blindness is generally associated with the loss of cone photoreceptors located in the central region of the retina called the macula. Currently, there is no treatment to replace the macula. Addressing this unmet need, we employed control isogenic and hypoimmunogenic induced pluripotent stem cell lines to generate spontaneously polarized retinal sheets (RSs). RSs were enriched in retinal progenitor and cone precursor cells, which could differentiate into mature S- and M/L-cones in long-term cultures. Single-cell RNA-seq analysis showed that RSs recapitulate the ontogeny of the developing human retina. Isolation of neural rosettes for sub-retinal transplantation effectively eliminated unwanted cells such as RPE cells. In a porcine model of chemically induced retinal degeneration, grafts integrated the host retina and formed a new, yet immature, photoreceptor layer. In one transplanted animal, functional and immunohistochemical assays suggest that grafts exhibited responsiveness to light stimuli and established putative synaptic connections with host bipolar neurons. This study underscores the potential and challenges of RSs for clinical applications.","PeriodicalId":11375,"journal":{"name":"Development","volume":"151 23","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lgr5 + intestinal stem cells are required for organoid survival after genotoxic injury. 基因毒性损伤后的类器官存活需要Lgr5+肠干细胞。

IF 3.7 2区生物学

Development Pub Date : 2024-12-01 Epub Date: 2024-11-29 DOI: 10.1242/dev.202941

Joseph Lee, Antoine Gleizes, Nicolas V Janto, Lito L Appell, Siyang Sun, Felipe Takaesu, Sarah F Webster, Taylor Hailstock, Nick Barker, Adam D Gracz

{"title":"Lgr5 + intestinal stem cells are required for organoid survival after genotoxic injury.","authors":"Joseph Lee, Antoine Gleizes, Nicolas V Janto, Lito L Appell, Siyang Sun, Felipe Takaesu, Sarah F Webster, Taylor Hailstock, Nick Barker, Adam D Gracz","doi":"10.1242/dev.202941","DOIUrl":"10.1242/dev.202941","url":null,"abstract":"Progenitors and mature cells can maintain the intestinal epithelium by dedifferentiation and facultative intestinal stem cell (fISC) function when active ISCs (aISCs) are lost to damage. Here, we modeled fISC activation in mouse intestinal organoids with doxorubicin (DXR) treatment, a chemotherapeutic known to ablate Lgr5+ aISCs in vivo. Similar fISC gene activation was observed between organoids treated with low versus high DXR, despite significantly decreased survival at the higher dose. aISCs exhibited dose-dependent loss after DXR treatment but survived at doses compatible with organoid survival. We ablated residual aISCs after DXR treatment using a Lgr52A-DTR allele and observed that aISC survival of the initial genotoxic insult is required for organoid survival following DXR treatment. These results suggest that although typical fISC genes are activated by DXR-induced injury in organoids, functional stemness remains dependent on the aISC pool. Finally, we show that human intestinal organoids require higher doses of DXR to induce loss of survival and downregulation of LGR5. Our data establish a reproducible model of DXR-induced injury in intestinal organoids and reveal differences in in vitro responses to an established in vivo damage modality.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular diversity of human inner ear organoids revealed by single-cell transcriptomics.

IF 3.7 2区生物学

Development Pub Date : 2024-12-01 Epub Date: 2024-11-29 DOI: 10.1242/dev.202524

Mireia Rumbo, Berta Alsina

引用次数: 0

Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos. 睾酮通过膜蛋白 GPRC6A 作用于斑马鱼胚胎，导致心脏水肿。

IF 3.7 2区生物学

Development Pub Date : 2024-12-01 Epub Date: 2024-11-29 DOI: 10.1242/dev.204390

Vahid Zadmajid, Shayan Shahriar, Daniel A Gorelick

{"title":"Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos.","authors":"Vahid Zadmajid, Shayan Shahriar, Daniel A Gorelick","doi":"10.1242/dev.204390","DOIUrl":"10.1242/dev.204390","url":null,"abstract":"Androgens are classically thought to act through intracellular androgen receptors (AR/NR3C4), but they can also trigger non-genomic effects via membrane proteins. Although several membrane androgen receptors have been characterized in vitro, their functions in vivo remain unclear. Using a chemical-genetic screen in zebrafish, we found that GPRC6A, a G-protein-coupled receptor, mediates non-genomic androgen actions during embryonic development. Exposure to androgens (androstanedione, DHT and testosterone) caused cardiac edema or tail curvature in wild-type embryos, as well as in ar mutants, suggesting AR-independent pathways. We then mutated putative membrane androgen receptors [gprc6a, hcar1-4 and zip9 (slc39a9)] and found that only gprc6a mutants exhibited a significant reduction in cardiac edema after testosterone exposure. Additionally, co-treatment of wild-type embryos with testosterone and GPRC6A antagonists significantly suppressed the cardiac edema phenotype. Using RNA-seq and RNA rescue approaches, we found that testosterone and GPRC6A cause cardiac phenotypes by reducing Pak1 signaling. Our results indicate that testosterone induces cardiac edema in zebrafish embryos through GPRC6A, independent of nuclear androgen receptors, highlighting a previously unappreciated non-genomic androgen signaling pathway in embryonic development.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0