Development最新文献_第2页

Examining the NEUROG2-lineage and associated-gene expression in human cortical organoids.

IF 3.7 2区生物学

Development Pub Date : 2024-12-16 DOI: 10.1242/dev.202703

Lakshmy Vasan, Vorapin Chinchalongporn, Fermisk Saleh, Dawn Zinyk, Cao Ke, Hamsini Suresh, Hussein Ghazale, Lauren Belfiore, Yacine Touahri, Ana-Maria Oproescu, Shruti Patel, Matthew Rozak, Yutaka Amemiya, Sisu Han, Alexandra Moffat, Sandra E Black, JoAnne McLaurin, Jamie Near, Arun Seth, Maged Goubran, Orly Reiner, Jesse Gillis, Chao Wang, Satoshi Okawa, Carol Schuurmans

{"title":"Examining the NEUROG2-lineage and associated-gene expression in human cortical organoids.","authors":"Lakshmy Vasan, Vorapin Chinchalongporn, Fermisk Saleh, Dawn Zinyk, Cao Ke, Hamsini Suresh, Hussein Ghazale, Lauren Belfiore, Yacine Touahri, Ana-Maria Oproescu, Shruti Patel, Matthew Rozak, Yutaka Amemiya, Sisu Han, Alexandra Moffat, Sandra E Black, JoAnne McLaurin, Jamie Near, Arun Seth, Maged Goubran, Orly Reiner, Jesse Gillis, Chao Wang, Satoshi Okawa, Carol Schuurmans","doi":"10.1242/dev.202703","DOIUrl":"https://doi.org/10.1242/dev.202703","url":null,"abstract":"Proneural genes are conserved drivers of neurogenesis across the animal kingdom. How their functions have adapted to guide human-specific neurodevelopmental features is poorly understood. Here, we mined transcriptomic data from human fetal cortices and generated from human embryonic stem cell (hESC)-derived cortical organoids (COs) to show that NEUROG1 and NEUROG2 are most highly expressed in basal neural progenitor cells, with pseudotime trajectory analyses indicating that NEUROG1-derived lineages predominate early and NEUROG2 lineages later. Using ChIP-qPCR, gene silencing and overexpression studies in COs, we show NEUROG2 is necessary and sufficient to directly transactivate known target genes (NEUROD1, EOMES, RND2). To identify new targets, we engineered NEUROG2-mCherry knock-in hESCs for CO generation. The mCherry-high CO cell transcriptome is enriched in extracellular matrix (ECM)-associated genes, and two genes associated with human-accelerated regions; PPP1R17 and FZD8. We show NEUROG2 binds COL1A1, COL3A1 and PPP1R17 regulatory elements and induces their ectopic expression in COs, although NEUROG2 is not required for this expression. Neurog2 similarly induces Col3a1 and Ppp1r17 in murine P19 cells. These data are consistent with a conservation of NEUROG2 function across mammalian species.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827604","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

CFI-1/ARID3 functions unilaterally to restrict gap junction formation in C. elegans. CFI-1/ARID3具有单侧功能，可限制优雅小鼠间隙连接的形成。

IF 3.7 2区生物学

Development Pub Date : 2024-12-16 DOI: 10.1242/dev.202955

Zan Wu, Lin Pang, Mei Ding

引用次数: 0

In vitro modelling of anterior primitive streak patterning with human pluripotent stem cells identifies the path to notochord progenitors.

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-12 DOI: 10.1242/dev.202983

Miguel Robles-Garcia, Chloë Thimonier, Konstantina Angoura, Ewa Ozga, Heather MacPherson, Guillaume Blin

{"title":"In vitro modelling of anterior primitive streak patterning with human pluripotent stem cells identifies the path to notochord progenitors.","authors":"Miguel Robles-Garcia, Chloë Thimonier, Konstantina Angoura, Ewa Ozga, Heather MacPherson, Guillaume Blin","doi":"10.1242/dev.202983","DOIUrl":"10.1242/dev.202983","url":null,"abstract":"Notochord progenitors (NotoPs) represent a scarce yet crucial embryonic cell population, playing important roles in embryo patterning and eventually giving rise to the cells that form and maintain intervertebral discs. The mechanisms regulating NotoPs emergence are unclear. This knowledge gap persists due to the inherent complexity of cell fate patterning during gastrulation, particularly within the anterior primitive streak (APS), where NotoPs first arise alongside neuro-mesoderm and endoderm. To gain insights into this process, we use micropatterning together with FGF and the WNT pathway activator CHIR9901 to guide the development of human embryonic stem cells into reproducible patterns of APS cell fates. We show that CHIR9901 dosage dictates the downstream dynamics of endogenous TGFβ signalling, which in turn controls cell fate decisions. While sustained NODAL signalling defines endoderm and NODAL inhibition is imperative for neuro-mesoderm emergence, timely inhibition of NODAL signalling with spatial confinement potentiates WNT activity and enables us to generate NotoPs efficiently. Our work elucidates the signalling regimes underpinning NotoP emergence and provides insights into the regulatory mechanisms controlling the balance of APS cell fates during gastrulation.","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/PMC11664173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750276","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 retinoic acid-binding proteins regulate germ cell proliferation and sex determination in zebrafish. 细胞视黄酸结合蛋白调控斑马鱼生殖细胞增殖和性别决定

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-13 DOI: 10.1242/dev.202549

Lianna Fung, Daniel B Dranow, Arul Subramanian, Natalia Libby, Thomas F Schilling

{"title":"Cellular retinoic acid-binding proteins regulate germ cell proliferation and sex determination in zebrafish.","authors":"Lianna Fung, Daniel B Dranow, Arul Subramanian, Natalia Libby, Thomas F Schilling","doi":"10.1242/dev.202549","DOIUrl":"10.1242/dev.202549","url":null,"abstract":"Cellular retinoic acid (RA)-binding proteins (Crabps) solubilize intracellular RA and transport it to its nuclear receptors or cytoplasmic degradation enzymes. Despite their extreme conservation across chordates, genetic studies of Crabp function have revealed few essential functions. We have generated loss-of-function mutations in all four zebrafish Crabps and find essential roles for Crabp2 proteins in gonad development and sex determination. Transgenic RA reporters show strong RA responses in germ cells at the bipotential stage of gonad development. Double mutants lacking the functions of both Crabp2a and Crabp2b predominantly become male, which correlates with their smaller gonad size and reduced germ cell proliferation during gonad development at late larval and early juvenile stages. In contrast, mutants lacking the functions of both Crabp1a and Crabp1b have normal sex ratios. Exogenous RA treatments at bipotential gonad stages increase germ cell number, consistent with a direct role for RA in promoting germ cell proliferation. Our results suggest essential functions for Crabps in gonad development and sex determination.","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/PMC11664166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686160","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

The sclerotome is the source of the dorsal and anal fin skeleton and its expansion is required for median fin development. 硬骨是背鳍和臀鳍骨骼的来源，中鳍的发育需要硬骨的扩张。

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-13 DOI: 10.1242/dev.203025

Raisa Bailon-Zambrano, Margaret K Keating, Emily C Sales, Abigail R Nichols, Grace E Gustafson, Colette A Hopkins, Katrinka M Kocha, Peng Huang, Lindsey Barske, James T Nichols

{"title":"The sclerotome is the source of the dorsal and anal fin skeleton and its expansion is required for median fin development.","authors":"Raisa Bailon-Zambrano, Margaret K Keating, Emily C Sales, Abigail R Nichols, Grace E Gustafson, Colette A Hopkins, Katrinka M Kocha, Peng Huang, Lindsey Barske, James T Nichols","doi":"10.1242/dev.203025","DOIUrl":"10.1242/dev.203025","url":null,"abstract":"Paired locomotion appendages are hypothesized to have redeployed the developmental program of median appendages, such as the dorsal and anal fins. Compared with paired fins, and limbs, median appendages remain surprisingly understudied. Here, we report that a dominant zebrafish mutant, smoothback (smb), fails to develop a dorsal fin. Moreover, the anal fin is reduced along the antero-posterior axis, and spine defects develop. Mechanistically, the smb mutation is caused by an insertion of a sox10:Gal4VP16 transgenic construct into a non-coding region. The first step in fin, and limb, induction is aggregation of undifferentiated mesenchyme at the appendage development site. In smb, this dorsal fin mesenchyme is absent. Lineage tracing demonstrates the previously unknown developmental origin of the mesenchyme, the sclerotome, which also gives rise to the spine. Strikingly, we find that there is significantly less sclerotome in smb than in wild type. Our results give insight into the origin and modularity of understudied median fins, which have changed position, number, size, and even disappeared, across evolutionary time.","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/PMC11664171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686167","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

Short-range Fgf signalling patterns hindbrain progenitors to induce the neurogenesis-to-oligodendrogenesis switch. 短程 Fgf 信号为后脑祖细胞提供模式，诱导神经发生向孤树突发生的转换。

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-13 DOI: 10.1242/dev.204256

Tim J Yeung, David G Wilkinson

{"title":"Short-range Fgf signalling patterns hindbrain progenitors to induce the neurogenesis-to-oligodendrogenesis switch.","authors":"Tim J Yeung, David G Wilkinson","doi":"10.1242/dev.204256","DOIUrl":"10.1242/dev.204256","url":null,"abstract":"In the vertebrate nervous system, neurogenesis generally precedes gliogenesis. The mechanisms driving the switch in cell type production and generation of the correct proportion of cell types remain unclear. Here, we show that Fgf20 signalling patterns progenitors to induce the switch from neurogenesis to oligodendrogenesis in the zebrafish hindbrain. Fgf20 emanating from earlier-born neurons signals at a short range to downregulate proneural gene expression in the segment centre with high spatial precision along both anterior-posterior and dorsal-ventral axes. This signal induces oligodendrocytes in the segment centre by upregulating olig2 and sox10 expression in pre-patterned competent progenitors. We show that the magnitude of proneural gene downregulation and the quantity of oligodendrocyte precursor cells specified is dependent on the extent of Fgf20 signalling. Overexpression of fgf20a induces precocious specification and differentiation of oligodendrocytes among olig2+ progenitors, resulting in an increase in oligodendrocytes at the expense of neurogenesis. Thus, Fgf20 signalling defines the proportion of each cell type produced. Taken together, Fgf20 signalling from earlier-born neurons patterns hindbrain segments spatially and temporally to induce the neurogenesis-to-oligodendrogenesis switch.","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/PMC11664172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686166","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

Hedgehog-dependent and hedgehog-independent roles for growth arrest specific 1 in mammalian kidney morphogenesis.

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-18 DOI: 10.1242/dev.203012

Nicole E Franks, Benjamin L Allen

引用次数: 0

A multidimensional toolkit for elucidating temporal trajectories in cell development in vivo.

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-18 DOI: 10.1242/dev.204255

Masahiro Ono, Tessa Crompton

{"title":"A multidimensional toolkit for elucidating temporal trajectories in cell development in vivo.","authors":"Masahiro Ono, Tessa Crompton","doi":"10.1242/dev.204255","DOIUrl":"10.1242/dev.204255","url":null,"abstract":"Progenitor cells initiate development upon receiving key signals, dynamically altering gene and protein expression to diverge into various lineages and fates. Despite the use of several experimental approaches, including the Fluorescent Timer-based method Timer-of-cell-kinetics-and-activity (Tocky), analysing time-dependent processes at the single-cell level in vivo remains challenging. This study introduces a novel integrated experimental and computational approach, using an advanced multidimensional toolkit. This toolkit facilitates the simultaneous examination of temporal progression and T-cell profiles using high-dimensional flow cytometric data. Employing novel algorithms based on canonical correspondence analysis and network analysis, our toolkit identifies developmental trajectories and analyses dynamic changes in developing cells. The efficacy of this approach is demonstrated by analysing thymic T cells from Nr4a3-Tocky mice, which monitor activities downstream of the T-cell receptor (TCR) signal. Further validation was achieved by deleting the proapoptotic gene Bcl2l11 in Nr4a3-Tocky mice. This revealed dynamic changes in thymic T cells during cellular development and negative selection following TCR signalling. Overall, this study establishes a new method for analysing the temporal dynamics of individual developing cells in response to in vivo signalling cues.","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":"142750274","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

Barcoding Notch signaling in the developing brain. 发育中大脑中 Notch 信号的条形码。

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-20 DOI: 10.1242/dev.203102

Abigail M Siniscalco, Roshan Priyarangana Perera, Jessie E Greenslade, Hemagowri Veeravenkatasubramanian, Aiden Masters, Hannah M Doll, Bushra Raj

{"title":"Barcoding Notch signaling in the developing brain.","authors":"Abigail M Siniscalco, Roshan Priyarangana Perera, Jessie E Greenslade, Hemagowri Veeravenkatasubramanian, Aiden Masters, Hannah M Doll, Bushra Raj","doi":"10.1242/dev.203102","DOIUrl":"10.1242/dev.203102","url":null,"abstract":"Developmental signaling inputs are fundamental for shaping cell fates and behavior. However, traditional fluorescent-based signaling reporters have limitations in scalability and molecular resolution of cell types. We present SABER-seq, a CRISPR-Cas molecular recorder that stores transient developmental signaling cues as permanent mutations in cellular genomes for deconstruction at later stages via single-cell transcriptomics. We applied SABER-seq to record Notch signaling in developing zebrafish brains. SABER-seq has two components: a signaling sensor and a barcode recorder. The sensor activates Cas9 in a Notch-dependent manner with inducible control, while the recorder obtains mutations in ancestral cells where Notch is active. We combine SABER-seq with an expanded juvenile brain atlas to identify cell types derived from Notch-active founders. Our data reveal rare examples where differential Notch activities in ancestral progenitors are detected in terminally differentiated neuronal subtypes. SABER-seq is a novel platform for rapid, scalable and high-resolution mapping of signaling activity during development.","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":"142686090","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

The Dlk1-Dio3 noncoding RNA cluster coordinately regulates mitochondrial respiration and chromatin structure to establish proper cell state for muscle differentiation.

IF 3.7 2区生物学

Development Pub Date : 2024-12-15 Epub Date: 2024-12-20 DOI: 10.1242/dev.203127

Amanda Pinheiro, Christopher A Petty, Chelsea E Stephens, Kevin Cabrera, Eric Palanques-Tost, Adam C Gower, Madison Marano, Ethan M Leviss, Matthew J Boberg, Jawahar Mahendran, Payton M Bock, Jessica L Fetterman, Francisco J Naya

{"title":"The Dlk1-Dio3 noncoding RNA cluster coordinately regulates mitochondrial respiration and chromatin structure to establish proper cell state for muscle differentiation.","authors":"Amanda Pinheiro, Christopher A Petty, Chelsea E Stephens, Kevin Cabrera, Eric Palanques-Tost, Adam C Gower, Madison Marano, Ethan M Leviss, Matthew J Boberg, Jawahar Mahendran, Payton M Bock, Jessica L Fetterman, Francisco J Naya","doi":"10.1242/dev.203127","DOIUrl":"10.1242/dev.203127","url":null,"abstract":"The coordinate regulation of metabolism and epigenetics to establish cell state-specific gene expression patterns during lineage progression is a central aspect of cell differentiation, but the factors that regulate this elaborate interplay are not well-defined. The imprinted Dlk1-Dio3 noncoding RNA (ncRNA) cluster has been associated with metabolism in various progenitor cells, suggesting it functions as a regulator of metabolism and cell state. Here, we directly demonstrate that the Dlk1-Dio3 ncRNA cluster coordinates mitochondrial respiration and chromatin structure to maintain proper cell state. Stable mouse muscle cell lines were generated harboring two distinct deletions in the proximal promoter region, resulting in either greatly upregulated or downregulated expression of the entire Dlk1-Dio3 ncRNA cluster. Both mutant lines displayed impaired muscle differentiation along with dysregulated structural gene expression and abnormalities in mitochondrial respiration. Genome-wide chromatin accessibility and histone methylation patterns were also severely affected in these mutants. Our results strongly suggest that muscle cells are sensitive to Dlk1-Dio3 ncRNA dosage, and that the cluster coordinately regulates metabolic activity and the epigenome to maintain proper cell state in the myogenic lineage.","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":"142750359","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