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The transcription factor LHX2 suppresses astrocyte proliferation in the postnatal mammalian cerebral cortex. 转录因子LHX2抑制出生后哺乳动物大脑皮层星形胶质细胞增殖。
IF 3.7 2区 生物学
Development Pub Date : 2025-10-15 Epub Date: 2025-06-02 DOI: 10.1242/dev.204358
Archana Iyer, Reanne Fronteiro, Prachi Bhatia, Sanjna Kumari, Amrita Singh, Jiafeng Zhou, Riccardo Bocchi, Rishikesh Narayanan, Shubha Tole
{"title":"The transcription factor LHX2 suppresses astrocyte proliferation in the postnatal mammalian cerebral cortex.","authors":"Archana Iyer, Reanne Fronteiro, Prachi Bhatia, Sanjna Kumari, Amrita Singh, Jiafeng Zhou, Riccardo Bocchi, Rishikesh Narayanan, Shubha Tole","doi":"10.1242/dev.204358","DOIUrl":"10.1242/dev.204358","url":null,"abstract":"<p><p>In the developing cerebral cortex, astrocytes arise from progenitors in the ventricular and subventricular zones (V-SVZ), and also from local proliferation within the parenchyma. In the mouse neocortex, astrocytes that occupy upper layers (UL) versus deep layers (DL) are known to be distinct populations in terms of molecular and morphological features. The transcription factor LHX2 is expressed both in V-SVZ gliogenic progenitors and in differentiated astrocytes throughout development and into adulthood. Here, we show that loss of Lhx2 at birth results in an increased astrocyte proliferation in the UL but not the DL of the cortex in the first postnatal week. Consistent with this, transcriptomic signatures of UL astrocytes increase. By 3 months, Lhx2 mutant astrocytes display upregulation of GFAP, and transcriptomic signatures associated with 'reactive' astrocytes, in the absence of injury. These results demonstrate a role for Lhx2 in regulating proliferation and molecular features of cortical astrocytes.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998797","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
A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex. 发育中的小鼠视觉皮层中感觉依赖基因表达的单细胞转录组图谱。
IF 3.7 2区 生物学
Development Pub Date : 2025-10-15 Epub Date: 2025-03-27 DOI: 10.1242/dev.204244
Andre M Xavier, Qianyu Lin, Chris J Kang, Lucas Cheadle
{"title":"A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex.","authors":"Andre M Xavier, Qianyu Lin, Chris J Kang, Lucas Cheadle","doi":"10.1242/dev.204244","DOIUrl":"10.1242/dev.204244","url":null,"abstract":"<p><p>Sensory experience drives the maturation of neural circuits during postnatal brain development through molecular mechanisms that remain to be fully elucidated. One likely mechanism involves the sensory-dependent expression of genes that encode direct mediators of circuit remodeling within developing cells. To identify potential drivers of sensory-dependent synaptic development, we generated a single-nucleus RNA sequencing dataset describing the transcriptional responses of cells in the mouse visual cortex to sensory deprivation or to stimulation during a developmental window when visual input is necessary for circuit refinement. We sequenced 118,529 nuclei across 16 neuronal and non-neuronal cell types isolated from control, sensory deprived and sensory stimulated mice, identifying 1268 sensory-induced genes within the developing brain. While experience elicited transcriptomic changes in all cell types, excitatory neurons in layer 2/3 exhibited the most robust changes, and the sensory-induced genes in these cells are poised to strengthen synapse-to-nucleus crosstalk and to promote cell type-specific axon guidance pathways. Altogether, we expect this dataset to significantly broaden our understanding of the molecular mechanisms through which sensory experience shapes neural circuit wiring in the developing brain.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523044","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
CSF1R ligands promote microglial proliferation but are not the sole regulators of developmental microglial proliferation. CSF-1R配体促进小胶质细胞增殖,但不是发育性小胶质细胞增殖的唯一调节因子。
IF 3.7 2区 生物学
Development Pub Date : 2025-10-15 Epub Date: 2025-06-03 DOI: 10.1242/dev.204610
Brady P Hammond, Sameera Zia, Eugene Hahn, Margarita Kapustina, Tristan Lange, Sarah Friesen, Rupali Manek, Kelly V Lee, Adrian Castellanos-Molina, Floriane Bretheau, Mark S Cembrowski, Bradley J Kerr, Steve Lacroix, Jason R Plemel
{"title":"CSF1R ligands promote microglial proliferation but are not the sole regulators of developmental microglial proliferation.","authors":"Brady P Hammond, Sameera Zia, Eugene Hahn, Margarita Kapustina, Tristan Lange, Sarah Friesen, Rupali Manek, Kelly V Lee, Adrian Castellanos-Molina, Floriane Bretheau, Mark S Cembrowski, Bradley J Kerr, Steve Lacroix, Jason R Plemel","doi":"10.1242/dev.204610","DOIUrl":"10.1242/dev.204610","url":null,"abstract":"<p><p>Microglia - the predominant immune cells of the brain and spinal cord - perform essential functions for the development and maintenance of the central nervous system, contingent upon the regulated developmental proliferation of microglia. However, the factor(s) that regulate microglial proliferation remain unclear. Here, we confirmed the timeline of developmental proliferation and used bioinformatics to identify potential signalling onto microglia in mouse from datasets collected at an age of high developmental microglial proliferation. Of the predicted factors, we found that colony stimulating factor 1 receptor (CSF1R) ligands boosted proliferation in vitro and were increasingly expressed in the brain across development with each displaying a distinct regional and temporal expression pattern. However, we did not observe a coincident alteration to CSF1R ligand levels in a model of abnormal developmental proliferation. Together, although CSF1R ligands can promote microglial proliferation in culture, their developmental expression patterns suggest that they function alongside other unknown factors to regulate developmental microglial proliferation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093051","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
Mesenchymal SLMAP coordinates with MST3 to govern gut elongation during development. 间充质SLMAP与MST3协同控制发育过程中的肠伸长。
IF 3.7 2区 生物学
Development Pub Date : 2025-06-16 DOI: 10.1242/dev.204483
Yuwei Pan, Shiyang Wang, Wuqi Yang, Xi Wu, Hanfu Zhang, Sujuan Du, Mingxin Zhang, Liyuan Hou, Maksim V Plikus, Jianwei Shuai, Cong Lv, Lu Yu, Zhengquan Yu
{"title":"Mesenchymal SLMAP coordinates with MST3 to govern gut elongation during development.","authors":"Yuwei Pan, Shiyang Wang, Wuqi Yang, Xi Wu, Hanfu Zhang, Sujuan Du, Mingxin Zhang, Liyuan Hou, Maksim V Plikus, Jianwei Shuai, Cong Lv, Lu Yu, Zhengquan Yu","doi":"10.1242/dev.204483","DOIUrl":"https://doi.org/10.1242/dev.204483","url":null,"abstract":"<p><p>Developing gut in mice undergoes rapid elongation during late embryogenesis, yet significantly slows down after birth. Precise regulatory mechanism of this dynamic morphogenetic process remains unknown. Utilizing single-cell RNA-sequencing analysis, we show that YAP activity in intestinal fibroblasts is the major molecular contributor to gut elongation. To determine how mesenchymal YAP activity is controlled, we identified canonical Sarcolemma membrane-associated protein (SLMAP) as its critical regulator during embryonic gut morphogenesis. Deleting Slmap in gut mesenchyme impairs YAP activity, leading to short gut and a significant decrease in intestinal epithelial cell proliferation. Mechanistically, SLMAP activates YAP by directly regulating MST3 kinase. Physiologically, MST3 levels prominently increase over the developmental time, reaching their peak on postnatal day P14, when gut elongation in mice slows down. Depleting Mst3 in mesenchyme results in increased gut length at P14 accompanied by enhanced YAP activity. Importantly, short gut phenotype in mesenchyme-specific Slmap mutant mice is partially compensated by concomitant deletion of mesenchymal Mst3. Taken together, our findings demonstrate that SLMAP interacts with MST3 kinase to dynamically regulate mesenchymal YAP activity that governs dynamic gut elongation across its embryonic and postnatal development.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301363","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
Serotonin neuromodulation directs optic nerve regeneration. 血清素神经调节指导视神经再生。
IF 3.7 2区 生物学
Development Pub Date : 2025-06-16 DOI: 10.1242/dev.204334
Kristian Saied-Santiago, Melissa Baxter, Jaffna Mathiaparanam, Michael Granato
{"title":"Serotonin neuromodulation directs optic nerve regeneration.","authors":"Kristian Saied-Santiago, Melissa Baxter, Jaffna Mathiaparanam, Michael Granato","doi":"10.1242/dev.204334","DOIUrl":"https://doi.org/10.1242/dev.204334","url":null,"abstract":"<p><p>Optic nerve (ON) regeneration in mammalian systems is limited by an overshadowing dominance of inhibitory factors. This has severely hampered the identification of pro-regenerative pathways. Here, we take advantage of the regenerative capacity of larval zebrafish to identify pathways that promote ON regeneration. From a small molecule screen, we identified modulators of serotonin (5-HT) signaling that inhibit ON regeneration. We find several serotonin type-1 receptor genes are expressed in RGC neurons during regeneration and that inhibiting 5-HT1 receptors or components of the 5-HT pathway selectively impedes ON regeneration. We show that 5-HT1 receptor signaling is dispensable during ON development yet is critical for regenerating axons to emerge from the injury site. Blocking 5-HT receptors once ON axons have crossed the chiasm does not inhibit regeneration, suggesting a selective role for 5-HT receptor signaling early during ON regeneration. Finally, we show that agonist-mediated activation of 5-HT1 receptors leads to enhanced and ectopic axonal regrowth. Combined, our results provide evidence for mechanisms through which serotonin-dependent neuromodulation directs ON regeneration in vivo.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301364","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
Polyphenisms: a developmental perspective. 多表型:一个发展的视角。
IF 3.7 2区 生物学
Development Pub Date : 2025-06-15 Epub Date: 2025-06-13 DOI: 10.1242/dev.204693
Peter K Dearden
{"title":"Polyphenisms: a developmental perspective.","authors":"Peter K Dearden","doi":"10.1242/dev.204693","DOIUrl":"https://doi.org/10.1242/dev.204693","url":null,"abstract":"<p><p>Polyphenisms, the production of two or more discrete phenotypes from a single genome, are a remarkable reflection of the flexibility of developmental mechanisms. Examples of polyphenisms include castes in eusocial insects, and winged versus wingless forms of aphids. How the signals that drive these alternate forms are received and interpreted, and how they trigger different developmental trajectories remains unknown. While different polyphenisms have evolved independently with different signals and outcomes, there are some commonalities that may help us understand the way development can be remodelled. In this Review, I discuss the relationship between plasticity and polyphenisms, and the role of neuro-endocrine signalling and epigenetic pathways. I focus on developmental polyphenisms, outlining current knowledge and unanswered questions regarding the underlying developmental mechanisms. To understand polyphenism mechanisms, we need functional experiments; I lay out a framework for interpreting such experiments. I hope to convince you that polyphenisms are an important topic of study for developmental biologists and that functional experiments may unlock a better understanding of the interplay between the environment and development, shedding light on how morphology evolves.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282945","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
KDM6B is a conserved activator at the top of the male sex determination pathway. KDM6B是一个保守的激活因子,位于雄性性别决定通路的顶端。
IF 3.7 2区 生物学
Development Pub Date : 2025-06-15 Epub Date: 2025-06-13 DOI: 10.1242/dev.204724
Shannon M Dupont, Alexandra Garcia-Moreno, Eleanore V O'Neil, Blanche C Capel
{"title":"KDM6B is a conserved activator at the top of the male sex determination pathway.","authors":"Shannon M Dupont, Alexandra Garcia-Moreno, Eleanore V O'Neil, Blanche C Capel","doi":"10.1242/dev.204724","DOIUrl":"10.1242/dev.204724","url":null,"abstract":"<p><p>In mammals, commitment to the testis fate is controlled by the gene Sry on the Y chromosome; however, how Sry is regulated is not well understood. In the red-eared slider turtle, Dmrt1 acts as the primary activator of the testis pathway. Removal of the repressive histone modification H3K27me3 from Dmrt1 by the histone demethylase KDM6B is required for its activation. We hypothesized that a similar de-repression mechanism is used in mammals to activate the testis pathway. Using a mouse knockout model for Kdm6b, we found that loss of Kdm6b leads to a delay in Sry activation and the development of an ovotestis. These results implicate KDM6B as a conserved regulator at the top of the sex determination cascade in both reptiles and mammals.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126801","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
In preprints: rethinking the foundations of the ovarian reserve. 预印本:重新思考卵巢储备的基础。
IF 3.7 2区 生物学
Development Pub Date : 2025-06-15 Epub Date: 2025-06-16 DOI: 10.1242/dev.204939
Andrea Rix, Binyam Mogessie
{"title":"In preprints: rethinking the foundations of the ovarian reserve.","authors":"Andrea Rix, Binyam Mogessie","doi":"10.1242/dev.204939","DOIUrl":"https://doi.org/10.1242/dev.204939","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301365","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
Transitions in development - an interview with Jan Żylicz. 开发中的过渡——对Jan Żylicz的采访。
IF 3.7 2区 生物学
Development Pub Date : 2025-06-15 Epub Date: 2025-06-13 DOI: 10.1242/dev.204949
{"title":"Transitions in development - an interview with Jan Żylicz.","authors":"","doi":"10.1242/dev.204949","DOIUrl":"https://doi.org/10.1242/dev.204949","url":null,"abstract":"<p><p>Jan Żylicz is an Associate Professor at the Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, within the University of Copenhagen, Denmark. Jan's work bridges the fields of epigenetics, chromatin and metabolism to understand the metabolic regulation of gene expression in stem cells and development. We met with Jan on Teams to learn more about working abroad, finding a good mentor and his career path so far.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282946","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
In preprints: unpicking chemical and mechanical crosstalk for axonal pathfinding. 预印本:为轴突寻径而分解化学和机械串扰。
IF 3.7 2区 生物学
Development Pub Date : 2025-06-15 Epub Date: 2025-06-13 DOI: 10.1242/dev.204948
Dionn Hargreaves, Sarah Woolner
{"title":"In preprints: unpicking chemical and mechanical crosstalk for axonal pathfinding.","authors":"Dionn Hargreaves, Sarah Woolner","doi":"10.1242/dev.204948","DOIUrl":"https://doi.org/10.1242/dev.204948","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282944","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
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