bioRxiv - Developmental Biology最新文献_第5页

Acute dietary methionine restriction highlights sensitivity of neocortex development to metabolic variations 急性蛋氨酸饮食限制凸显了新皮层发育对代谢变化的敏感性

bioRxiv - Developmental Biology Pub Date : 2024-09-12 DOI: 10.1101/2024.09.10.612174

Sulov Saha, Clemence Debacq, Christophe Audouard, Thomas Jungas, Pierrick Dupre, Mohamad Ali Fawal, Clement Chapat, Henri-Alexandre Michaud, Laurent Le Cam, Matthieu Lacroix, David Ohayon, Alice Davy

{"title":"Acute dietary methionine restriction highlights sensitivity of neocortex development to metabolic variations","authors":"Sulov Saha, Clemence Debacq, Christophe Audouard, Thomas Jungas, Pierrick Dupre, Mohamad Ali Fawal, Clement Chapat, Henri-Alexandre Michaud, Laurent Le Cam, Matthieu Lacroix, David Ohayon, Alice Davy","doi":"10.1101/2024.09.10.612174","DOIUrl":"https://doi.org/10.1101/2024.09.10.612174","url":null,"abstract":"Methionine, an essential amino acid that has to be provided by nutrition, and its metabolite S-Adenosyl methionine (SAM) are indispensable for cell proliferation, stem cell maintenance and epigenetic regulation, three processes that are central to embryonic development. Previous studies using chronic dietary restriction of methyl donors prior to and during gestation indicated that methionine restriction (MR) is detrimental to the development or growth of the neocortex, however, the consequences of acute MR have not been extensively studied. Here, we designed a dietary MR regime coinciding with the neurogenic phases of neocortex development in the mouse. Our results indicate that dietary MR for 5 days leads to a severe reduction in neocortex growth and neuronal production. In comparison, growth of the liver and heart was unaffected, highlighting an organ-specific response to MR which was also observed at the cellular and molecular levels. Progenitor cohort labeling revealed a time-dependent sensitivity to MR and cell cycle analyses indicated that after 5 days of MR, progenitors are stalled in the S/G2 phases. Unexpectedly, neocortex growth reduction induced after 5 days of MR is completely rescued at birth when switching the dam back to control diet for the remaining of gestation, uncovering a mechanism of catch-up growth. Using multiplexed imaging we probed metabolic and epigenetic markers following MR and during catch-up growth and show that pyruvate metabolism is rewired in progenitors. Altogether, our data uncover a transient state of quiescence in G2/S which is metabolically distinct from G0 quiescence and associated with efficient catch-up growth. More globally, our study highlights both the extreme sensitivity of the developing neocortex to acute dietary changes and its remarkable plasticity.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"247 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

gilgamesh, Drosophila casein kinase 1g, is required for myosin-dependent junction strengthening and epithelial folding 果蝇酪蛋白激酶 1g gilgamesh 是肌球蛋白依赖性连接强化和上皮折叠的必要条件

bioRxiv - Developmental Biology Pub Date : 2024-09-12 DOI: 10.1101/2024.09.11.612545

Lingkun Gu, Reina Benefiel, Jasneet Brar, Mo Weng

引用次数: 0

Axin1 and Axin2 regulate the WNT-signaling landscape to promote distinct mesoderm programs Axin1和Axin2调节WNT信号图谱以促进不同的中胚层程序

bioRxiv - Developmental Biology Pub Date : 2024-09-11 DOI: 10.1101/2024.09.11.612342

Rocío Hernández-Martínez, Sonja Nowotschin, Luke T.G. Harland, Ying-Yi Kuo, Bart Theeuwes, Berthold Göttgens, Elizabeth Lacy, Anna-Katerina Hadjantonakis, Kathryn V. Anderson

{"title":"Axin1 and Axin2 regulate the WNT-signaling landscape to promote distinct mesoderm programs","authors":"Rocío Hernández-Martínez, Sonja Nowotschin, Luke T.G. Harland, Ying-Yi Kuo, Bart Theeuwes, Berthold Göttgens, Elizabeth Lacy, Anna-Katerina Hadjantonakis, Kathryn V. Anderson","doi":"10.1101/2024.09.11.612342","DOIUrl":"https://doi.org/10.1101/2024.09.11.612342","url":null,"abstract":"How distinct mesodermal lineages- extraembryonic, lateral, intermediate, paraxial and axial- are specified from pluripotent epiblast during gastrulation is a longstanding open question. By investigating AXIN, a negative regulator of the WNT/β-catenin pathway, we have uncovered new roles for WNT signaling in the determination of mesodermal fates. We undertook complementary approaches to dissect the role of WNT signaling that augmented a detailed analysis of Axin1;Axin2 mutant mouse embryos, including single-cell and single-embryo transcriptomics, with in vitro pluripotent Epiblast-Like Cell differentiation assays. This strategy allowed us to reveal two layers of regulation. First, WNT initiates differentiation of primitive streak cells into mesoderm progenitors, and thereafter, WNT amplifies and cooperates with BMP/pSMAD1/5/9 or NODAL/pSMAD2/3 to propel differentiating mesoderm progenitors into either posterior streak derivatives or anterior streak derivatives, respectively. We propose that Axin1 and Axin2 prevent aberrant differentiation of pluripotent epiblast cells into mesoderm by spatially and temporally regulating WNT signaling levels","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The chromatin remodeler DEK promotes proliferation of mammary epithelium and is associated with H3K27me3 epigenetic modifications 染色质重塑剂 DEK 能促进乳腺上皮细胞的增殖，并与 H3K27me3 表观遗传修饰有关

bioRxiv - Developmental Biology Pub Date : 2024-09-10 DOI: 10.1101/2024.09.09.612116

Megan Johnstone, Ashley Leck, Taylor E Lange, Katherine E Wilcher, Miranda S Shephard, Aditi Paranjpe, Sophia Schutte, Susanne I Wells, Ferdinand Kappes, Nathan Salomonis, Lisa M Privette Vinnedge

{"title":"The chromatin remodeler DEK promotes proliferation of mammary epithelium and is associated with H3K27me3 epigenetic modifications","authors":"Megan Johnstone, Ashley Leck, Taylor E Lange, Katherine E Wilcher, Miranda S Shephard, Aditi Paranjpe, Sophia Schutte, Susanne I Wells, Ferdinand Kappes, Nathan Salomonis, Lisa M Privette Vinnedge","doi":"10.1101/2024.09.09.612116","DOIUrl":"https://doi.org/10.1101/2024.09.09.612116","url":null,"abstract":"The DEK chromatin remodeling protein was previously shown to confer oncogenic phenotypes to human and mouse mammary epithelial cells using in vitro and knockout mouse models. However, its functional role in normal mammary gland epithelium remained unexplored. We developed two novel mouse models to study the role of Dek in normal mammary gland biology in vivo. Mammary gland-specific Dek over-expression in mice resulted in hyperproliferation of cells that visually resembled alveolar cells, and a transcriptional profile that indicated increased expression of cell cycle, mammary stem/progenitor, and lactation-associated genes. Conversely, Dek knockout mice exhibited an alveologenesis or lactation defect, resulting in dramatically reduced pup survival. Analysis of previously published single-cell RNA-sequencing of mouse mammary glands revealed that Dek is most highly expressed in mammary stem cells and alveolar progenitor cells, and to a lesser extent in basal epithelial cells, supporting the observed phenotypes. Mechanistically, we discovered that Dek is a modifier of Ezh2 methyltransferase activity, upregulating the levels of histone H3 trimethylation on lysine 27 (H3K27me3) to control gene transcription. Combined, this work indicates that Dek promotes proliferation of mammary epithelial cells via cell cycle deregulation. Furthermore, we report a novel function for Dek in alveologenesis and histone H3 K27 trimethylation.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Robinow Syndrome DVL1 mutations disrupt morphogenesis and appendage formation in a Drosophila disease model 罗宾诺综合征 DVL1 突变破坏果蝇疾病模型的形态发生和附肢形成

bioRxiv - Developmental Biology Pub Date : 2024-09-10 DOI: 10.1101/2024.09.10.612347

Gamze Akarsu, Katja R MacCharles, Kenneth Kin Lam Wong, Joy Richman, Esther M. Verheyen

{"title":"Robinow Syndrome DVL1 mutations disrupt morphogenesis and appendage formation in a Drosophila disease model","authors":"Gamze Akarsu, Katja R MacCharles, Kenneth Kin Lam Wong, Joy Richman, Esther M. Verheyen","doi":"10.1101/2024.09.10.612347","DOIUrl":"https://doi.org/10.1101/2024.09.10.612347","url":null,"abstract":"Robinow Syndrome is a rare developmental syndrome caused by mutations in numerous genes involved in Wnt signaling pathways. We previously showed that expression of patient variants in Drosophila and a chicken model disrupts the balance of canonical and non-canonical/PCP Wnt signaling. We also noted neomorphic effects that warranted further investigation. In this study, we examine morphological changes that occur as a result of one variant, DVL11519ΔT, that serves as a prototype for the other mutations. We show that epithelial imaginal disc development is disrupted in legs and wings. Shortened leg segments are reminiscent of shortened limb bones seen in RS patients. We find that imaginal disc development is disrupted and accompanied by increased cell death, without changes in cell proliferation. Furthermore, we find altered dynamics of basement membrane components and modulators. Notably we find increased MMP1 expression and tissue distortion, which is dependent on Jnk signaling. We also find enhanced collagen IV (Viking) secreted from cells expressing DVL11519ΔT. Through these studies we have gained more insight into developmental consequences of DVL1 mutations implicated in autosomal dominant Robinow Syndrome.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroendocrine Control of Intestinal Regeneration Through the Vascular Niche in Drosophila. 神经内分泌通过果蝇的血管龛位控制肠道再生

bioRxiv - Developmental Biology Pub Date : 2024-09-10 DOI: 10.1101/2024.09.10.612352

Andre Medina, Jessica Perochon, Julia B Cordero

{"title":"Neuroendocrine Control of Intestinal Regeneration Through the Vascular Niche in Drosophila.","authors":"Andre Medina, Jessica Perochon, Julia B Cordero","doi":"10.1101/2024.09.10.612352","DOIUrl":"https://doi.org/10.1101/2024.09.10.612352","url":null,"abstract":"Robust and controlled intestinal regeneration is essential for the preservation of organismal health and wellbeing and involves reciprocal interactions between the intestinal epithelium and its microenvironment. While knowledge of regulatory roles of the microenvironment on the intestine is vast, how distinct perturbations within the intestinal epithelium may influence tailored responses from the microenvironment, remains understudied. Here, we present previously unknown signaling between enteroendocrine cells, vasculature-like trachea, and neurons, which drives regional and global stem cell proliferation during adult intestinal regeneration in Drosophila.\u0000Injury-induced ROS from midgut epithelial cells promotes the production and secretion of Dh31, the homolog of mammalian Calcitonin Gene-Related Peptide (CGRP), from anterior midgut EE cells. Dh31 from EE cells and neurons signal to Dh31 receptor within TTCs leading to cell autonomous production of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-like Pvf1. Tracheal derived Pvf1 induces remodeling of the tracheal stem cell niche and regenerative ISC proliferation through autocrine and paracrine Pvr/MAPK signalling, respectively. Interestingly, while EE Dh31 exerts broad control of ISC proliferation throughout the midgut, functions of the neuronal source of the ligand appear restricted to the posterior midgut. Altogether, our work has led to the discovery of a novel enteroendocrine/neuronal/vascular signaling network controlling global and domain specific ISC proliferation during adult intestinal regeneration.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell-type-specific splicing of transcription regulators and Ptbp1 by Rbfox1/2/3 in the developing neocortex 在发育中的新皮层中，Rbfox1/2/3对转录调节因子和Ptbp1进行细胞类型特异性剪接

bioRxiv - Developmental Biology Pub Date : 2024-09-10 DOI: 10.1101/2024.09.09.612108

Xiangbin Ruan, Kaining Hu, Yalan Yang, Runwei Yang, Elizabeth Tseng, Bowei Kang, Aileen Kauffman, Rong Zhong, Xiaochang Zhang

{"title":"Cell-type-specific splicing of transcription regulators and Ptbp1 by Rbfox1/2/3 in the developing neocortex","authors":"Xiangbin Ruan, Kaining Hu, Yalan Yang, Runwei Yang, Elizabeth Tseng, Bowei Kang, Aileen Kauffman, Rong Zhong, Xiaochang Zhang","doi":"10.1101/2024.09.09.612108","DOIUrl":"https://doi.org/10.1101/2024.09.09.612108","url":null,"abstract":"How master splicing regulators crosstalk with each other and to what extent transcription regulators are differentially spliced remain unclear in the developing brain. Here, cell-type-specific RNA-Seq of the developing neocortex uncover that transcription regulators are enriched for differential splicing, altering protein isoforms or inducing nonsense-mediated mRNA decay. Transient expression of Rbfox proteins in radial glia progenitors induces neuronal splicing events preferentially in transcription regulators such as Meis2 and Tead1. Surprisingly, Rbfox proteins promote the inclusion of a mammal-specific alternative exon and a previously undescribed poison exon in Ptbp1. Simultaneous ablation of Rbfox1/2/3 in the neocortex downregulates neuronal isoforms and disrupts radial neuronal migration. Furthermore, the progenitor isoform of Meis2 promotes Tgfb3 transcription, while the Meis2 neuron isoform promotes neuronal differentiation. These observations indicate that transcription regulators are differentially spliced between cell types in the developing neocortex.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"256 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Axolotl epigenetic clocks offer insights into the nature of negligible senescence 轴叶虫表观遗传时钟揭示了可忽略衰老的本质

bioRxiv - Developmental Biology Pub Date : 2024-09-10 DOI: 10.1101/2024.09.09.611397

Yuliia Haluza, Joseph A Zoller, Ake T Lu, Hannah E Walters, Martina Lachnit, Robert Lowe, Amin Haghani, Robert T Brooke, Naomi Park, Maximina H Yun, Steve Horvath

{"title":"Axolotl epigenetic clocks offer insights into the nature of negligible senescence","authors":"Yuliia Haluza, Joseph A Zoller, Ake T Lu, Hannah E Walters, Martina Lachnit, Robert Lowe, Amin Haghani, Robert T Brooke, Naomi Park, Maximina H Yun, Steve Horvath","doi":"10.1101/2024.09.09.611397","DOIUrl":"https://doi.org/10.1101/2024.09.09.611397","url":null,"abstract":"Renowned for their regenerative abilities, axolotls also exhibit exceptional longevity, resistance to age-related diseases and apparent lack of physiological declines through lifespan, and have thus been considered organisms of negligible senescence. Whether axolotls display epigenetic hallmarks of ageing remains unknown. Here, we probe the axolotl DNA methylome throughout lifespan and present its first epigenetic clocks. Both at tissue-specific or pan-tissue levels, the clocks are biphasic, capable of predicting age during early life but not for the rest of its lifespan. We show that axolotls exhibit evolutionarily conserved features of epigenetic ageing during early life, yet their methylome is remarkably stable across lifespan, including at Polycomb Repressive Complex 2 (PRC2) target sites, suggesting that this species deviates from known patterns of epigenetic ageing. Lastly, we uncover structure-specific rejuvenation events upon regeneration. This study provides molecular insights into negligible senescence and furthers our understanding of the interplay between regeneration and ageing.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"264 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic priming of embryonic enhancer elements coordinates developmental gene networks 胚胎增强子元件的表观遗传引物协调发育基因网络

bioRxiv - Developmental Biology Pub Date : 2024-09-10 DOI: 10.1101/2024.09.09.611867

Christopher D Todd, Jannat Ijaz, Fereshteh Torabi, Oleksandr Dovgusha, Stephen Bevan, Olivia Cracknell, Tim Lohoff, Stephen Clark, Ricard Argelaguet, Juliette Pearce, Ioannis Kafetzopoulos, Alice Santambrogio, Jennifer Nichols, Ferdinand von Meyenn, Ufuk Guenesdogan, Stefan Schoenfelder, Wolf Reik

{"title":"Epigenetic priming of embryonic enhancer elements coordinates developmental gene networks","authors":"Christopher D Todd, Jannat Ijaz, Fereshteh Torabi, Oleksandr Dovgusha, Stephen Bevan, Olivia Cracknell, Tim Lohoff, Stephen Clark, Ricard Argelaguet, Juliette Pearce, Ioannis Kafetzopoulos, Alice Santambrogio, Jennifer Nichols, Ferdinand von Meyenn, Ufuk Guenesdogan, Stefan Schoenfelder, Wolf Reik","doi":"10.1101/2024.09.09.611867","DOIUrl":"https://doi.org/10.1101/2024.09.09.611867","url":null,"abstract":"Embryonic development requires the accurate spatiotemporal execution of cell lineage-specific gene expression programs, which are controlled by transcriptional enhancers. Developmental enhancers adopt a primed chromatin state prior to their activation; however, how this primed enhancer state is established, maintained, and how it affects the regulation of developmental gene networks remains poorly understood. Here, we use comparative multi-omic analyses of human and mouse early embryonic development to identify subsets of post-gastrulation lineage-specific enhancers which are epigenetically primed ahead of their activation, marked by the histone modification H3K4me1 within the epiblast. We show that epigenetic priming occurs at lineage-specific enhancers for all three germ layers, and that epigenetic priming of enhancers confers lineage-specific regulation of key developmental gene networks. Surprisingly in some cases, lineage-specific enhancers are epigenetically marked already in the zygote, weeks before their activation during lineage specification. Moreover, we outline a generalisable strategy to use naturally occurring human genetic variation to delineate important sequence determinants of primed enhancer function. Our findings identify an evolutionarily conserved program of enhancer priming and begin to dissect the temporal dynamics and mechanisms of its establishment and maintenance during early mammalian development.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gonadotrophs have a dual origin, with most derived from pituitary stem cells during minipuberty. 促性腺激素有双重来源，大部分来自未成年时的垂体干细胞。

bioRxiv - Developmental Biology Pub Date : 2024-09-10 DOI: 10.1101/2024.09.09.610834

Daniel Sheridan, Probir Chakravarty, Gil Golan, Yiolanda Shiakola, Christophe Galichet, Patrice Mollard, Philippa Melamed, Robin Lovell-Badge, Karine Rizzoti

引用次数: 0