{"id":341,"title":"Gastruloids reveal alternative morphogenetic routes for body-axis elongation with distinct cytoskeletal dependencies","title_zh":"类原肠胚揭示体轴延长的替代形态发生路径及其对细胞骨架的不同依赖","url":"https://pubmed.ncbi.nlm.nih.gov/42993568","doi":"10.1073/pnas.2606813123","pmid":"42993568","journal":"Proc Natl Acad Sci U S A","kind":"paper","lang":"en","published_at":"2026-11-06T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Serrano Nájera G","Delahaye A","Steventon BJ"],"primary_topic":"early-embryo","topics":[{"slug":"early-embryo","score":4.0,"hits":["gastruloids"]},{"slug":"omics-methods","score":1.0,"hits":["transcriptomic"]}],"topic_score":4.0,"preference_score":6.0,"preference_labels":["干细胞胚胎模型（blastoid / gastruloid 等）"],"llm_score":74.0,"final_score":86.0,"score_dims":{"novelty":82,"rigor":78,"impact":72,"relevance":58,"translation":56},"recommend_reason":"用类原肠胚把“环境-力学效应器-形态发生策略”的因果关系拆解清楚，对理解哺乳动物体轴延长与胚胎模型可重复性有直接价值；但属发育力学基础研究，与临床 ART 决策距离较远。","keywords":["类原肠胚","体轴延长","细胞骨架","formin","层粘连蛋白","集体细胞迁移"],"selected":1,"story_id":18,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":2,"has_interpretation":false,"journal_key":"pnas","journal_tier":"general-top","journal_if":9.4,"is_mock":false,"summary_zh":"研究利用可在体外控制环境线索的小鼠类原肠胚（gastruloid）模型，探讨细胞如何选择体轴延长的力学策略。结果显示底物可获得性决定力学生成方式：自由悬浮时类原肠胚通过细胞间相互作用自组装出单一后部体轴；铺于层粘连蛋白（laminin）上则变为扁平形态、多次打破对称，并以集体细胞迁移形成多条独立延长的细胞流，具前后极性。铺板条件下组织延长依赖 formin 活性与黏着斑介导的牵张力，而悬浮条件下二者均可缺失。转录组分析显示抑制 formin 在层粘连蛋白上阻断延长却无转录变化，提示其作用主要为力学性的、仅在细胞接触底物时才需要；层粘连蛋白还使细胞偏向后方迁移命运而 Hox 表达谱基本保持。","summary":"Morphogenesis requires cells to integrate genetic and environmental information to pattern and shape tissues. Recent studies in vivo and in vitro have shown how alterations in environmental cues can induce alternative morphogenetic programs. However, what determines which morphogenetic strategy cells deploy in different environments remains unknown. Using gastruloids, a model for mammalian posterior body-axis elongation where environmental cues can be controlled in vitro, we show that substrate availability determines which force-generation strategy cells employ to build the body axis. In free-floating conditions, gastruloids self-assemble a single posterior body axis, presumably through cell-cell interactions. When plated on laminin, gastruloids acquire a flat morphology, break symmetry multiple times, and produce several independently elongating cell streams with anterior-posterior polarity through collective cell migration. On laminin, formin activity and focal adhesion-mediated traction are required for tissue elongation, yet both are functionally dispensable in free-floating conditions. Transcriptomic analysis shows that formin inhibition blocks elongation on laminin without any detectable transcriptional changes, indicating that these cytoskeletal components play primarily a mechanical role that is only required when cells engage a substrate. Furthermore, laminin biases cells toward posterior migratory fates while preserving similar Hox expression. Together, these results show that mammalian body-axis elongation can proceed through different morphogenetic modes that engage distinct mechanical effectors depending on substrate availability. These findings have implications for understanding how evolution explores morphological diversity and how tissue engineering might achieve desired forms through precise environmental control.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}