Development最新文献_第6页

Conserved roles of engrailed: patterning tissues and specifying cell types. 遗传基因的保守作用：塑造组织和指定细胞类型。

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-13 DOI: 10.1242/dev.204250

Alexandra L Joyner, João Ramalho Ortigão-Farias, Thomas Kornberg

引用次数: 0

The people behind the papers - Amanda Pinheiro and Francisco Naya. 这些报纸背后的人，阿曼达·皮涅罗和弗朗西斯科·纳亚。

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-20 DOI: 10.1242/dev.204579

引用次数: 0

Phospho-regulation of ASCL1-mediated chromatin opening during cellular reprogramming. 细胞重编程过程中 ASCL1 介导的染色质开放的磷酸调控。

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-12 DOI: 10.1242/dev.204329

Roberta Azzarelli, Sarah Gillen, Frances Connor, Jethro Lundie-Brown, Francesca Puletti, Rosalind Drummond, Ana Raffaelli, Anna Philpott

{"title":"Phospho-regulation of ASCL1-mediated chromatin opening during cellular reprogramming.","authors":"Roberta Azzarelli, Sarah Gillen, Frances Connor, Jethro Lundie-Brown, Francesca Puletti, Rosalind Drummond, Ana Raffaelli, Anna Philpott","doi":"10.1242/dev.204329","DOIUrl":"10.1242/dev.204329","url":null,"abstract":"The proneural transcription factor ASCL1 regulates neurogenesis and drives somatic cell reprogramming into neurons. However, not all cell types can be reprogrammed by ASCL1, raising the questions of what provides competence and how we can overcome barriers to enable directed differentiation. Here, we investigate how levels of ASCL1 and its phosphorylation modulate its activity over progressive lineage restriction of mouse embryonic stem cells. We find that inhibition of ASCL1 phosphorylation enhances reprogramming of both mesodermal and neuroectodermal cells, while pluripotent cells remain refractory to ASCL1-directed neuronal differentiation. By performing RNA-seq and ATAC-seq in neuroectoderm, we find that un(der)phosphorylated ASCL1 causes increased chromatin accessibility at sites proximal to neuronal genes, accompanied by their increased expression. Combined analysis of protein stability and proneural function of phosphomutant and phosphomimetic ASCL1 reveals that protein stability plays only a marginal role in regulating activity, while changes in amino acid charge cannot fully explain enhanced activity of the serine-proline mutant variants of ASCL1. Our work provides new insights into proneural factor activity and regulation, and suggests ways to optimize reprogramming protocols in cancer and regenerative medicine.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686161","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

A simple MiMIC-based approach for tagging endogenous genes to visualise live transcription in Drosophila. 一种基于 MiMIC 的简单方法，用于标记内源基因以可视化果蝇的实时转录。

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-16 DOI: 10.1242/dev.204294

Lauren Forbes Beadle, Catherine Sutcliffe, Hilary L Ashe

{"title":"A simple MiMIC-based approach for tagging endogenous genes to visualise live transcription in Drosophila.","authors":"Lauren Forbes Beadle, Catherine Sutcliffe, Hilary L Ashe","doi":"10.1242/dev.204294","DOIUrl":"10.1242/dev.204294","url":null,"abstract":"Live imaging of transcription in the Drosophila embryo using the MS2 or PP7 systems is transforming our understanding of transcriptional regulation. However, insertion of MS2/PP7 stem-loops into endogenous genes requires laborious CRISPR genome editing. Here, we exploit the previously described Minos-mediated integration cassette (MiMIC) transposon system in Drosophila to establish a method for simply and rapidly inserting MS2/PP7 cassettes into any of the thousands of genes carrying a MiMIC insertion. In addition to generating a variety of stem-loop donor fly stocks, we have made new stocks expressing the complementary coat proteins fused to different fluorescent proteins. We show the utility of this MiMIC-based approach by MS2/PP7 tagging of endogenous genes and the long non-coding RNA roX1, then imaging their transcription in living embryos. We also present live transcription data from larval brains, the wing disc and ovary, thereby extending the tissues that can be studied using the MS2/PP7 system. Overall, this first high-throughput method for tagging mRNAs in Drosophila will facilitate the study of transcription dynamics of thousands of endogenous genes in a range of Drosophila tissues.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709333","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

Temporal dynamics of BMP/Nodal ratio drive tissue-specific gastrulation morphogenesis. BMP/结比的时间动态驱动组织特异性原肠胚形态发生。

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

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. Flt1失活通过增强内皮活性和限制纤维化反应来促进斑马鱼心脏再生。

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

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

Molecular characterization and sub-retinal transplantation of hypoimmunogenic human retinal sheets in a minipig model of severe photoreceptor degeneration. 低免疫原性人视网膜片在严重光感受器变性小型猪模型中的分子表征和视网膜下移植。

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

Cellular diversity of human inner ear organoids revealed by single-cell transcriptomics. 单细胞转录组学揭示人内耳类器官的细胞多样性。

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