Differentiation最新文献

Comprehensive defect detection in mouse embryos and the heart by combining automated phenotyping with novel population averages and atlases 综合缺陷检测在小鼠胚胎和心脏结合自动表型与新群体平均和地图集

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2026-01-23 DOI: 10.1016/j.diff.2026.100936

Ella M.M.A. Martin , Kyle Drover , Anton Shpak , Neil R. Horner , Victoria O'Reilly , Emma Cocking , Joelene A. Greasby , Kavitha R. Iyer , Ruth Arkell , Sally L. Dunwoodie , Gavin Chapman

Micro-CT has become the standard for the assessment of malformations in mouse embryos because it allows the visualisation of internal structures in the context of the intact embryo. Statistical comparison of volume differences is possible via manual segmentation of organs of interest from micro-CT scans, but this process is slow and laborious. Automated registration-based methods now exist that make the volumetric analysis of all organs feasible. Here, we expand the available atlases for use with the LAMA registration and analysis pipeline to include high-resolution population averages derived from phosphotungstic acid-stained C57BL/6J embryos and corresponding manually segmented atlases at embryonic stage (E) 12.5, E15.5, and E17.5. We report application of these population averages and atlases with the LAMA phenotyping pipeline to Wbp11 heterozygous null embryos, identifying defects previously reported in the cervical vertebrae, brain, nasal cavity, palate, liver and kidneys as well as a right aortic arch defects missed by manual analysis, and volume differences in the eyes and spinal cord. Finally, we report a high-resolution isolated E18.5 mouse heart population average and corresponding atlas that when applied to the Wbp11 line identified significant differences. These findings highlight the advantages of unbiased, volumetric and quantitative approaches in the analysis of mouse models of human disease.

Micro-CT已成为评估小鼠胚胎畸形的标准，因为它允许在完整胚胎的背景下可视化内部结构。体积差异的统计比较是可能的，通过人工分割感兴趣的器官从显微ct扫描，但这个过程是缓慢和费力的。现在存在基于自动注册的方法，使所有器官的体积分析成为可能。在这里，我们扩展了可用的图谱用于LAMA注册和分析管道，包括来自磷钨酸染色的C57BL/6J胚胎的高分辨率种群平均值和相应的胚胎期(E) 12.5, E15.5和E17.5的人工分割图谱。我们报告了将这些群体平均值和图谱与LAMA表型管道应用于Wbp11杂合零胚胎，确定了以前报道的颈椎、脑、鼻腔、腭、肝脏和肾脏的缺陷，以及手工分析遗漏的右主动脉弓缺陷，以及眼睛和脊髓的体积差异。最后，我们报告了高分辨率分离的E18.5小鼠心脏种群平均值和相应的图谱，当应用于Wbp11系时，发现了显著差异。这些发现突出了无偏、体积和定量方法在分析人类疾病小鼠模型中的优势。

{"title":"Comprehensive defect detection in mouse embryos and the heart by combining automated phenotyping with novel population averages and atlases","authors":"Ella M.M.A. Martin , Kyle Drover , Anton Shpak , Neil R. Horner , Victoria O'Reilly , Emma Cocking , Joelene A. Greasby , Kavitha R. Iyer , Ruth Arkell , Sally L. Dunwoodie , Gavin Chapman","doi":"10.1016/j.diff.2026.100936","DOIUrl":"10.1016/j.diff.2026.100936","url":null,"abstract":"<div><div>Micro-CT has become the standard for the assessment of malformations in mouse embryos because it allows the visualisation of internal structures in the context of the intact embryo. Statistical comparison of volume differences is possible via manual segmentation of organs of interest from micro-CT scans, but this process is slow and laborious. Automated registration-based methods now exist that make the volumetric analysis of all organs feasible. Here, we expand the available atlases for use with the LAMA registration and analysis pipeline to include high-resolution population averages derived from phosphotungstic acid-stained C57BL/6J embryos and corresponding manually segmented atlases at embryonic stage (E) 12.5, E15.5, and E17.5. We report application of these population averages and atlases with the LAMA phenotyping pipeline to <em>Wbp11</em> heterozygous null embryos, identifying defects previously reported in the cervical vertebrae, brain, nasal cavity, palate, liver and kidneys as well as a right aortic arch defects missed by manual analysis, and volume differences in the eyes and spinal cord. Finally, we report a high-resolution isolated E18.5 mouse heart population average and corresponding atlas that when applied to the <em>Wbp11</em> line identified significant differences. These findings highlight the advantages of unbiased, volumetric and quantitative approaches in the analysis of mouse models of human disease.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"148 ","pages":"Article 100936"},"PeriodicalIF":2.6,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Her9 is required for the migration, differentiation, and survival of neural crest cells Her9是神经嵴细胞迁移、分化和存活所必需的

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2026-01-01 DOI: 10.1016/j.diff.2026.100935

Cagney E. Coomer , Sumanth Manohar , Evelyn M. Turnbaugh , Ann C. Morris

Neural crest cells (NCC) are vertebrate-specific multipotent progenitor cells that arise from the neural plate border and go on to contribute to a wide variety of morphological structures such as the jaw and palate, enteric nervous system (ENS), and pigment cells. Defects in essential steps in neural crest cell development have been associated with a wide variety of congenital disorders, collectively referred to as neurocristopathies. Her9/Hes4 is a bHLH-O transcriptional repressor that has been shown to regulate neural crest cell and craniofacial development in Xenopus and zebrafish, however the extent of Her9 function in other neural crest cell lineages has not been investigated. In this study, we characterized NCC phenotypes in her9 mutant zebrafish. We show that loss of Her9 perturbs the development of several NCC derivatives. Her9 mutants display a variety of NCC defects, including craniofacial abnormalities, alterations in pigment cell lineages, and improper formation of the gut. These phenotypes are associated with defects in neural crest cell specification, migration, and differentiation, as well as an upregulation in expression of BMP ligand genes. Furthermore, loss of Her9 leads to apoptosis of NCC derivatives. Collectively, our results show that Her9 functions in neural crest development by regulating members of the NCC gene regulatory network (GRN) to control NCC specification, migration, differentiation and survival.

神经嵴细胞（NCC）是脊椎动物特有的多能祖细胞，起源于神经板边界，并继续促进各种形态结构，如颌和腭，肠神经系统（ENS）和色素细胞。神经嵴细胞发育的基本步骤缺陷与各种先天性疾病有关，统称为神经嵴病变。Her9/Hes4是一种bhhl - o转录抑制因子，已被证明可调节爪蟾和斑马鱼的神经嵴细胞和颅面发育，但Her9在其他神经嵴细胞系中的功能程度尚未被研究。在这项研究中，我们对her9突变斑马鱼的NCC表型进行了表征。我们发现Her9的缺失干扰了几种NCC衍生物的发展。Her9突变体表现出多种NCC缺陷，包括颅面异常、色素细胞系改变和肠道形成不当。这些表型与神经嵴细胞规范、迁移和分化的缺陷以及BMP配体基因表达的上调有关。此外，Her9的缺失导致NCC衍生物的凋亡。总之，我们的研究结果表明，Her9通过调节NCC基因调控网络（GRN）的成员来控制NCC的规范、迁移、分化和存活，从而在神经嵴发育中发挥作用。

{"title":"Her9 is required for the migration, differentiation, and survival of neural crest cells","authors":"Cagney E. Coomer , Sumanth Manohar , Evelyn M. Turnbaugh , Ann C. Morris","doi":"10.1016/j.diff.2026.100935","DOIUrl":"10.1016/j.diff.2026.100935","url":null,"abstract":"<div><div>Neural crest cells (NCC) are vertebrate-specific multipotent progenitor cells that arise from the neural plate border and go on to contribute to a wide variety of morphological structures such as the jaw and palate, enteric nervous system (ENS), and pigment cells. Defects in essential steps in neural crest cell development have been associated with a wide variety of congenital disorders, collectively referred to as neurocristopathies. Her9/Hes4 is a bHLH-O transcriptional repressor that has been shown to regulate neural crest cell and craniofacial development in Xenopus and zebrafish, however the extent of Her9 function in other neural crest cell lineages has not been investigated. In this study, we characterized NCC phenotypes in <em>her9</em> mutant zebrafish. We show that loss of Her9 perturbs the development of several NCC derivatives. <em>Her9</em> mutants display a variety of NCC defects, including craniofacial abnormalities, alterations in pigment cell lineages, and improper formation of the gut. These phenotypes are associated with defects in neural crest cell specification, migration, and differentiation, as well as an upregulation in expression of BMP ligand genes. Furthermore, loss of Her9 leads to apoptosis of NCC derivatives. Collectively, our results show that Her9 functions in neural crest development by regulating members of the NCC gene regulatory network (GRN) to control NCC specification, migration, differentiation and survival.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"147 ","pages":"Article 100935"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Development and proteome characterization of a new muscle cell line from Oreochromis niloticus (Linnaeus, 1758) 一种新的nilochromis肌肉细胞系的发育和蛋白质组学特征。

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2026-01-01 DOI: 10.1016/j.diff.2026.100934

Vijay Lakshmi Sahoo, A. Sathiyanarayanan, Nevil Pinto, Gowhar Iqbal, B.S. Yashwanth, Arvind A. Sonwane, Kiran D. Rasal, Mukunda Goswami

A new muscle cell line was developed and characterized from Genetically Improved Farmed Tilapia named as ONM (Oreochromis niloticus muscle) using the explant technique. The developed muscle cell line was well maintained in an L-15 medium supplemented with 5 % FBS at 28 °C with 10 ng/ml of bFGF. The growth pattern was studied by incubating the cells at different temperatures and FBS concentrations. The cell plating efficiency was 19 %, and the cell doubling time of ONM cells was 36 h. The transfection of ONM cells for the transgene expression using vector DNA was found positive with green fluorescent signal, 24 h post-transfection with 6 % efficiency. The mitochondrial gene sequences were used to authenticate the origin of the developed fish cell line. Protein-protein interaction and enrichment analysis of ONM revealed P10 involved the proliferation process (cytoplasm, muscle contraction), and P20 identified the insulin pathway, regulation of actin cytoskeleton, hedgehog on state, signalling by WNT, citrate cycle and VEGFA-VEGFR2 pathways, indicating cells were differentiated during later passages. In common proteins, chaperone, biosynthesis of amino acids, porin activity, and fin regeneration are crucial for the proliferation and differentiation process. The newly developed muscle cells from O. niloticus were adapted to grow in reduced serum conditions. The cell line developed can have a wide range of applications in in-vitro studies, including lab-grown meat, as well as a roadmap for the scientific and technological advancements needed to advance cellular aquaculture into a mainstream food source.

利用外植体技术，对养殖罗非鱼的肌肉细胞系ONM （Oreochromis niloticus muscle）进行了鉴定。发育的肌肉细胞系在28°C的L-15培养基中添加5% FBS和10 ng/ml bFGF，得到良好的维持。通过不同温度和FBS浓度的培养，研究了细胞的生长模式。细胞电镀效率为19%，ONM细胞的细胞倍增时间为36 h。转染ONM细胞用载体DNA进行转基因表达，转染24 h后发现绿色荧光信号阳性，转染效率为6%。线粒体基因序列用于鉴定发育的鱼细胞系的起源。蛋白-蛋白相互作用和ONM富集分析显示P10参与增殖过程（细胞质、肌肉收缩），P20识别胰岛素通路、肌动蛋白细胞骨架调控、hedgehog on状态、WNT信号通路、柠檬酸循环和VEGFA-VEGFR2通路，提示细胞在后期传代过程中发生分化。在普通蛋白质中，伴侣蛋白、氨基酸的生物合成、孔蛋白活性和鳍的再生对增殖和分化过程至关重要。新发展的肌肉细胞从niloticus适应在减少血清条件下生长。开发的细胞系可以在体外研究中有广泛的应用，包括实验室培养的肉类，以及将细胞水产养殖推进为主流食物来源所需的科学和技术进步路线图。

{"title":"Development and proteome characterization of a new muscle cell line from Oreochromis niloticus (Linnaeus, 1758)","authors":"Vijay Lakshmi Sahoo, A. Sathiyanarayanan, Nevil Pinto, Gowhar Iqbal, B.S. Yashwanth, Arvind A. Sonwane, Kiran D. Rasal, Mukunda Goswami","doi":"10.1016/j.diff.2026.100934","DOIUrl":"10.1016/j.diff.2026.100934","url":null,"abstract":"<div><div>A new muscle cell line was developed and characterized from Genetically Improved Farmed Tilapia named as ONM (<em>Oreochromis niloticus</em> muscle) using the explant technique. The developed muscle cell line was well maintained in an L-15 medium supplemented with 5 % FBS at 28 °C with 10 ng/ml of bFGF. The growth pattern was studied by incubating the cells at different temperatures and FBS concentrations. The cell plating efficiency was 19 %, and the cell doubling time of ONM cells was 36 h. The transfection of ONM cells for the transgene expression using vector DNA was found positive with green fluorescent signal, 24 h post-transfection with 6 % efficiency. The mitochondrial gene sequences were used to authenticate the origin of the developed fish cell line. Protein-protein interaction and enrichment analysis of ONM revealed P10 involved the proliferation process (cytoplasm, muscle contraction), and P20 identified the insulin pathway, regulation of actin cytoskeleton, hedgehog on state, signalling by WNT, citrate cycle and VEGFA-VEGFR2 pathways, indicating cells were differentiated during later passages. In common proteins, chaperone, biosynthesis of amino acids, porin activity, and fin regeneration are crucial for the proliferation and differentiation process. The newly developed muscle cells from <em>O. niloticus</em> were adapted to grow in reduced serum conditions. The cell line developed can have a wide range of applications in <em>in-vitro</em> studies, including lab-grown meat, as well as a roadmap for the scientific and technological advancements needed to advance cellular aquaculture into a mainstream food source.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"147 ","pages":"Article 100934"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Integrating biochemical cues and mechanical forces in stem cell-epithelial differentiation 在干细胞上皮分化中整合生化线索和机械力。

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2026-01-01 DOI: 10.1016/j.diff.2026.100931

Siti Nurnasihah Md Hashim , Sarahani Harun , Ahmad Sukari Halim , Suzina Sheikh Abdul Hamid , Thirumulu Ponnuraj Kannan , Khairul Bariah Ahmad Amin Noordin , Nazia Abdul Majid , Ahmad Azlina

Epithelial differentiation from stem cells is fundamental to regenerative medicine, with applications ranging from skin repair to epithelial tissue engineering. While traditionally guided by biochemical regulators such as retinoic acid (RA) and growth factors, the mechanical microenvironment is a critical, yet often underrepresented regulator of epithelial fate. This review addresses the knowledge gap by examining how chemical and mechanical cues cooperate to guide epithelial commitment across both conventional two-dimensional (2D) and advanced three-dimensional (3D) culture models. We specifically focus on the mechanism of mechanotransduction, detailing how mechanical forces are converted into biochemical signals. This process relies on specialized mechanosensitive mediators such as focal adhesion, ion channels, and cell-cell adhesion molecules. These inputs converge on the central Hippo-YAP/TAZ transcriptional hub, which acts as the primary mechanical sensor to modulate lineage trajectories. This integration reshapes how cells interpret signals through the major regulatory network (WNT, Notch, and TGFβ pathways) while balancing stemness against epithelial differentiation. Addressing this integrated mechanobiological perspective is essential for improving mechanistic understanding and reproducibility in stem cell-epithelial differentiation protocols. Incorporating dynamic mechanical conditioning and scaffold design into protocols is critical to advancing translational potential for regenerative applications.

从干细胞分化上皮细胞是再生医学的基础，其应用范围从皮肤修复到上皮组织工程。虽然传统上由维甲酸（RA）和生长因子等生化调节剂引导，但机械微环境是上皮命运的关键调节剂，但通常未被充分代表。这篇综述通过研究化学和机械线索如何在传统的二维（2D）和先进的三维（3D）培养模型中合作指导上皮细胞的承诺来解决知识差距。我们特别关注机械转导的机制，详细介绍了机械力如何转化为生化信号。这一过程依赖于特殊的机械敏感介质，如病灶粘附、离子通道和细胞-细胞粘附分子。这些输入集中在中央希波- yap /TAZ转录中心，它作为调节谱系轨迹的主要机械传感器。这种整合重塑了细胞如何通过主要调控网络（WNT、Notch和TGFβ通路）解释信号，同时平衡干细胞与上皮分化。解决这种综合的机械生物学观点对于提高干细胞上皮分化方案的机制理解和可重复性至关重要。将动态机械调节和支架设计纳入方案对于推进再生应用的转化潜力至关重要。

{"title":"Integrating biochemical cues and mechanical forces in stem cell-epithelial differentiation","authors":"Siti Nurnasihah Md Hashim , Sarahani Harun , Ahmad Sukari Halim , Suzina Sheikh Abdul Hamid , Thirumulu Ponnuraj Kannan , Khairul Bariah Ahmad Amin Noordin , Nazia Abdul Majid , Ahmad Azlina","doi":"10.1016/j.diff.2026.100931","DOIUrl":"10.1016/j.diff.2026.100931","url":null,"abstract":"<div><div>Epithelial differentiation from stem cells is fundamental to regenerative medicine, with applications ranging from skin repair to epithelial tissue engineering. While traditionally guided by biochemical regulators such as retinoic acid (RA) and growth factors, the mechanical microenvironment is a critical, yet often underrepresented regulator of epithelial fate. This review addresses the knowledge gap by examining how chemical and mechanical cues cooperate to guide epithelial commitment across both conventional two-dimensional (2D) and advanced three-dimensional (3D) culture models. We specifically focus on the mechanism of mechanotransduction, detailing how mechanical forces are converted into biochemical signals. This process relies on specialized mechanosensitive mediators such as focal adhesion, ion channels, and cell-cell adhesion molecules. These inputs converge on the central Hippo-YAP/TAZ transcriptional hub, which acts as the primary mechanical sensor to modulate lineage trajectories. This integration reshapes how cells interpret signals through the major regulatory network (WNT, Notch, and TGFβ pathways) while balancing stemness against epithelial differentiation. Addressing this integrated mechanobiological perspective is essential for improving mechanistic understanding and reproducibility in stem cell-epithelial differentiation protocols. Incorporating dynamic mechanical conditioning and scaffold design into protocols is critical to advancing translational potential for regenerative applications.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"147 ","pages":"Article 100931"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

CEK8/Ephrin-A4 defines the tendon field boundary through WNT–TGF-β crosstalk in the chicken embryo CEK8/Ephrin-A4通过WNT-TGF-β串扰定义鸡胚肌腱场边界。

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2026-01-01 DOI: 10.1016/j.diff.2026.100932

Jessica Cristina Marín-Llera, Claudio Ivan Galván-Hernández, Carlos Amaury Jiménez-Cárdenas, Jesus Chimal-Monroy

The development of tendons in vertebrate limbs occurs through the precise regulation of genes and signaling pathways between the skeletal elements and the ectoderm. Although it is known that SCX is a crucial regulator of tendon development, the establishment and maintenance of the tenogenic regions remain unclear. This study explores the role of CEK8 (Ephrin-A4) in early tendon differentiation in the chicken limb and its interaction with WNT/β-catenin and TGF-β pathways during tendon blastema formation. Our results show that Cek8 expression mirrors Scx in the developing tendon blastema but is localized at the boundary of SCX-positive cells. Inhibiting CEK8 upregulates Scx and other tenogenic genes; however, the effects are not sustained, indicating that CEK8 initially suppresses but later supports tenogenic differentiation. Through functional assays using protein-soaked beads in the tendon blastema, we determined that WNT signaling initially upregulates but later inhibits Cek8 expression in a time-dependent manner. TGF-β signaling induces a wider Cek8 expression domain compared to Scx, while CEK8 is necessary for the effects of TGF-β to maintain Scx induction. Inhibiting CEK8 expands the β-catenin and SMAD2/3 regions, favoring a tenogenic phenotype. These results identify CEK8 as a regulator of tendon progenitor architecture, likely involved in establishing positional information, which functions in association with WNT and TGF-β to control tenogenic differentiation both spatially and temporally. Our study provides new insights into the morphogenetic signals and cell interactions that occur during chicken tendon development.

脊椎动物四肢肌腱的发育是通过骨骼和外胚层之间的基因和信号通路的精确调控而发生的。虽然已知SCX是肌腱发育的关键调节因子，但肌腱发生区域的建立和维持尚不清楚。本研究探讨了CEK8 （Ephrin-A4）在鸡肢体早期肌腱分化中的作用及其在肌腱胚形成过程中与WNT/β-catenin和TGF-β通路的相互作用。我们的研究结果表明，Cek8的表达在发育中的肌腱胚中反映了Scx，但局限于Scx阳性细胞的边界。抑制CEK8可上调Scx和其他致癌基因；然而，这种影响并不是持续的，这表明CEK8最初抑制但后来支持肌腱分化。通过在肌腱囊母中使用蛋白浸泡珠的功能分析，我们确定WNT信号最初上调，但随后以时间依赖性的方式抑制Cek8的表达。与Scx相比，TGF-β信号诱导的Cek8表达域更宽，而Cek8是TGF-β维持Scx诱导作用所必需的。抑制CEK8扩展了β-连环蛋白和SMAD2/3区域，有利于形成致衰老表型。这些结果表明CEK8是肌腱祖细胞结构的调节因子，可能参与位置信息的建立，其与WNT和TGF-β相关，在空间和时间上控制肌腱分化。我们的研究为鸡腱发育过程中发生的形态发生信号和细胞相互作用提供了新的见解。

{"title":"CEK8/Ephrin-A4 defines the tendon field boundary through WNT–TGF-β crosstalk in the chicken embryo","authors":"Jessica Cristina Marín-Llera, Claudio Ivan Galván-Hernández, Carlos Amaury Jiménez-Cárdenas, Jesus Chimal-Monroy","doi":"10.1016/j.diff.2026.100932","DOIUrl":"10.1016/j.diff.2026.100932","url":null,"abstract":"<div><div>The development of tendons in vertebrate limbs occurs through the precise regulation of genes and signaling pathways between the skeletal elements and the ectoderm. Although it is known that SCX is a crucial regulator of tendon development, the establishment and maintenance of the tenogenic regions remain unclear. This study explores the role of CEK8 (Ephrin-A4) in early tendon differentiation in the chicken limb and its interaction with WNT/β-catenin and TGF-β pathways during tendon blastema formation. Our results show that <em>Cek8</em> expression mirrors <em>Scx</em> in the developing tendon blastema but is localized at the boundary of SCX-positive cells. Inhibiting CEK8 upregulates <em>Scx</em> and other tenogenic genes; however, the effects are not sustained, indicating that CEK8 initially suppresses but later supports tenogenic differentiation. Through functional assays using protein-soaked beads in the tendon blastema, we determined that WNT signaling initially upregulates but later inhibits <em>Cek8</em> expression in a time-dependent manner. TGF-β signaling induces a wider <em>Cek8</em> expression domain compared to <em>Scx</em>, while CEK8 is necessary for the effects of TGF-β to maintain Scx induction. Inhibiting CEK8 expands the β-catenin and SMAD2/3 regions, favoring a tenogenic phenotype. These results identify CEK8 as a regulator of tendon progenitor architecture, likely involved in establishing positional information, which functions in association with WNT and TGF-β to control tenogenic differentiation both spatially and temporally. Our study provides new insights into the morphogenetic signals and cell interactions that occur during chicken tendon development.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"147 ","pages":"Article 100932"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 regulation of the Ihh-PTHrP signaling axis modulates condylar development via angiogenesis Ihh-PTHrP信号轴的时间调控通过血管生成调节髁突发育

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2026-01-01 DOI: 10.1016/j.diff.2026.100933

Chuanqing Mao , Yunpeng Weng , Wenjie Zhou , Zuhui Li , Yongzhen Lai , Chengyong Wang , Meng Lu , Weihui Chen

Vismodegib, a Smoothened (Smo) receptor antagonist, effectively suppresses Hedgehog (Hh) signaling activity during embryonic development and is known to influence craniofacial morphogenesis. However, its specific role in temporomandibular joint (TMJ) development remains unclear. In this study, a single dose of vismodegib (150 mg/kg) was administered to pregnant mice at embryonic day 14.5 (E14.5) to investigate its impact on fetal TMJ morphogenesis. At postnatal day 21, offspring from the treatment group exhibited significantly reduced condylar length and bone surface area density compared to vehicle-treated controls. Despite no observable differences in cellular proliferation or apoptosis—as assessed by phospho-Histone H3 (PHH3) and TUNEL assays—angiogenic markers, including VEGF, CD31, and CD34, were markedly upregulated in the condylar region of vismodegib-treated mice. Furthermore, at E15.5, expression of key components of the Ihh-PTHrP signaling axis (Gli1, Ptch1, and PTHrP) was significantly downregulated in the experimental group relative to controls. These findings suggest that vismodegib disrupts TMJ development by inhibiting the Ihh-PTHrP signaling pathway, thereby altering angiogenesis in the condyle and ultimately impairing cartilage growth and structural integrity.

Vismodegib是一种Smoothened （Smo）受体拮抗剂，在胚胎发育过程中有效抑制Hedgehog （Hh）信号活性，并且已知会影响颅面形态发生。然而，其在颞下颌关节（TMJ）发育中的具体作用尚不清楚。本研究采用单剂量（150 mg/kg）维莫替吉（vismodegib）给药于胚胎期14.5天（E14.5）的妊娠小鼠，研究其对胎儿TMJ形态发生的影响。在出生后第21天，实验组的子代与对照组相比，髁突长度和骨表面积密度明显减少。尽管通过磷酸化组蛋白H3 （PHH3）和TUNEL检测没有观察到细胞增殖或凋亡的差异，但血管生成标志物，包括VEGF， CD31和CD34，在粘模吉治疗的小鼠的髁突区域显着上调。此外，在E15.5时，实验组Ihh-PTHrP信号轴的关键组分（Gli1、Ptch1和PTHrP）的表达相对于对照组显著下调。这些发现表明，vismodegib通过抑制Ihh-PTHrP信号通路来破坏TMJ的发育，从而改变髁突的血管生成，最终损害软骨生长和结构完整性。

{"title":"Temporal regulation of the Ihh-PTHrP signaling axis modulates condylar development via angiogenesis","authors":"Chuanqing Mao , Yunpeng Weng , Wenjie Zhou , Zuhui Li , Yongzhen Lai , Chengyong Wang , Meng Lu , Weihui Chen","doi":"10.1016/j.diff.2026.100933","DOIUrl":"10.1016/j.diff.2026.100933","url":null,"abstract":"<div><div>Vismodegib, a <em>Smoothened (Smo)</em> receptor antagonist, effectively suppresses <em>Hedgehog (Hh)</em> signaling activity during embryonic development and is known to influence craniofacial morphogenesis. However, its specific role in temporomandibular joint (TMJ) development remains unclear. In this study, a single dose of vismodegib (150 mg/kg) was administered to pregnant mice at embryonic day 14.5 (E14.5) to investigate its impact on fetal TMJ morphogenesis. At postnatal day 21, offspring from the treatment group exhibited significantly reduced condylar length and bone surface area density compared to vehicle-treated controls. Despite no observable differences in cellular proliferation or apoptosis—as assessed by <em>phospho-Histone H3 (PHH3)</em> and TUNEL assays—angiogenic markers, including <em>VEGF</em>, <em>CD31</em>, and <em>CD34</em>, were markedly upregulated in the condylar region of vismodegib-treated mice. Furthermore, at E15.5, expression of key components of the <em>Ihh</em>-<em>PTHrP</em> signaling axis (<em>Gli1</em>, <em>Ptch1</em>, and <em>PTHrP)</em> was significantly downregulated in the experimental group relative to controls. These findings suggest that vismodegib disrupts TMJ development by inhibiting the <em>Ihh</em>-<em>PTHrP</em> signaling pathway, thereby altering angiogenesis in the condyle and ultimately impairing cartilage growth and structural integrity.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"147 ","pages":"Article 100933"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Odd-skipped family members have conserved roles in segmentation, appendage, excretory system and gut development in bilaterian animals 奇数跳过家族成员在双边动物的分割、附属物、排泄系统和肠道发育中具有保守的作用。

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-12-12 DOI: 10.1016/j.diff.2025.100930

Vasikar Murugapoopathy , Claire Ramsay , Ehab Abouheif , Indra R. Gupta

The odd-skipped related family of proteins are evolutionarily conserved zinc finger transcription factors in bilaterian animals with essential roles in body segmentation, as well as gut, excretory system and appendage development. Although they are prognostic biomarkers in several cancers, their molecular function is poorly understood. To gain a deeper understanding of how this family of transcription factors is implicated in human disorders and cancer, we explore the functions of Odd-skipped related transcription factors as well as their invertebrate homologs during development. We found that vertebrate Osr1 binds to DNA targets within the WNT, BMP, HH, TGFβ, Notch and retinoic acid signaling pathways, suggesting that Osr genes coordinate and integrate multiple pathways during development, potentially by binding to heterochromatin as pioneer transcription factors. From a protein tree analysis of odd-skipped family orthologs and paralogs, it appears that vertebrate, nematode, and insect paralogues have arisen via independent gene duplication events, and that their common ancestor likely had a single odd-family gene. We hypothesize that the ancestral odd-family protein was required for gut and gut-derived structures and was subsequently co-opted to perform additional functions in other tissues as part of the evolution of organisms. These observations posit new uncharacterized functions for Osr genes in the development of bilaterian animals and in cancer models.

odd-skip相关蛋白家族是双侧动物中进化保守的锌指转录因子，在身体分割、肠道、排泄系统和附属物发育中起重要作用。虽然它们是几种癌症的预后生物标志物，但它们的分子功能尚不清楚。为了更深入地了解这一转录因子家族如何与人类疾病和癌症有关，我们探索了odd -skip相关转录因子及其在无脊椎动物发育过程中的同源物的功能。我们发现脊椎动物Osr1与WNT、BMP、HH、TGFβ、Notch和视黄酸信号通路中的DNA靶点结合，表明Osr基因在发育过程中协调和整合了多种途径，可能通过与异染色质结合作为先驱转录因子。通过对奇跳过家族直系物和类似物的蛋白质树分析，我们发现脊椎动物、线虫和昆虫的类似物是通过独立的基因复制事件产生的，它们的共同祖先很可能只有一个奇跳过家族基因。我们假设，这种古老的奇家族蛋白是肠道和肠道衍生结构所必需的，随后作为生物体进化的一部分，在其他组织中被选择执行其他功能。这些观察结果表明，Osr基因在双侧动物和癌症模型的发育中具有新的未表征的功能。

{"title":"Odd-skipped family members have conserved roles in segmentation, appendage, excretory system and gut development in bilaterian animals","authors":"Vasikar Murugapoopathy , Claire Ramsay , Ehab Abouheif , Indra R. Gupta","doi":"10.1016/j.diff.2025.100930","DOIUrl":"10.1016/j.diff.2025.100930","url":null,"abstract":"<div><div>The odd-skipped related family of proteins are evolutionarily conserved zinc finger transcription factors in bilaterian animals with essential roles in body segmentation, as well as gut, excretory system and appendage development. Although they are prognostic biomarkers in several cancers, their molecular function is poorly understood. To gain a deeper understanding of how this family of transcription factors is implicated in human disorders and cancer, we explore the functions of Odd-skipped related transcription factors as well as their invertebrate homologs during development. We found that vertebrate Osr1 binds to DNA targets within the WNT, BMP, HH, TGFβ, Notch and retinoic acid signaling pathways, suggesting that <em>Osr</em> genes coordinate and integrate multiple pathways during development, potentially by binding to heterochromatin as pioneer transcription factors. From a protein tree analysis of odd-skipped family orthologs and paralogs, it appears that vertebrate, nematode, and insect paralogues have arisen via independent gene duplication events, and that their common ancestor likely had a single odd-family gene. We hypothesize that the ancestral odd-family protein was required for gut and gut-derived structures and was subsequently co-opted to perform additional functions in other tissues as part of the evolution of organisms. These observations posit new uncharacterized functions for <em>Osr</em> genes in the development of bilaterian animals and in cancer models.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"147 ","pages":"Article 100930"},"PeriodicalIF":2.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Long non-coding RNA SNHG6 promotes odontoblastic differentiation of human dental pulp stem cells via the PI3K/Akt/mTOR pathway 长链非编码RNA SNHG6通过PI3K/Akt/mTOR通路促进人牙髓干细胞成牙细胞分化

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-12-05 DOI: 10.1016/j.diff.2025.100927

Wantong Zhang , Yan Zhou , Lin Ye , Chengsusu Huang , Yao Wang

Small nucleolar RNA host gene 6 (SNHG6) is a long non-coding RNA (lncRNA) that has been widely implicated in cellular processes such as proliferation, migration, and differentiation. This study investigated its role in the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). qRT-PCR analysis revealed that SNHG6 expression increased during odontoblastic differentiation. In hDPSCs, SNHG6 was primarily localized in the cytoplasm. Functional studies using knockdown and overexpression demonstrated that SNHG6 positively regulates odontoblastic differentiation, as evidenced by alkaline phosphatase activity, Alizarin Red S staining, and the expression of differentiation markers DSPP and DMP-1. However, CCK-8 assays revealed SNHG6 had no significant impact on cell proliferation, and wound healing assays similarly showed it did not influence cell migration. Mechanistically, pathway inhibitors LY294002 and Rapamycin were used. Western blot analysis confirmed that SNHG6 promotes odontoblastic differentiation by activating the PI3K/Akt/mTOR signaling pathway, as shown by changes in phosphorylated Akt, mTOR, S6K1, and 4EBP1 levels. These findings highlight SNHG6 as a key regulator of hDPSC differentiation through PI3K/Akt/mTOR signaling, offering new insights into the molecular mechanisms controlling odontoblast formation.

小核核RNA宿主基因6 （SNHG6）是一种长链非编码RNA (lncRNA)，广泛参与细胞增殖、迁移和分化等过程。本研究探讨了其在人牙髓干细胞（hDPSCs）成牙细胞分化中的作用。qRT-PCR分析显示，SNHG6在成牙细胞分化过程中表达增加。在hDPSCs中，SNHG6主要定位于细胞质中。通过敲低和过表达的功能研究表明，SNHG6正调控成牙细胞分化，碱性磷酸酶活性、茜素红S染色、分化标记物DSPP和DMP-1的表达均证实了这一点。然而，CCK-8实验显示SNHG6对细胞增殖没有显著影响，伤口愈合实验同样显示它不影响细胞迁移。机制上使用途径抑制剂LY294002和雷帕霉素。Western blot分析证实，SNHG6通过激活PI3K/Akt/mTOR信号通路促进成牙细胞分化，如磷酸化Akt、mTOR、S6K1和4EBP1水平的变化。这些发现强调了SNHG6是通过PI3K/Akt/mTOR信号传导调控hDPSC分化的关键调控因子，为研究成牙细胞形成的分子机制提供了新的见解。

{"title":"Long non-coding RNA SNHG6 promotes odontoblastic differentiation of human dental pulp stem cells via the PI3K/Akt/mTOR pathway","authors":"Wantong Zhang , Yan Zhou , Lin Ye , Chengsusu Huang , Yao Wang","doi":"10.1016/j.diff.2025.100927","DOIUrl":"10.1016/j.diff.2025.100927","url":null,"abstract":"<div><div>Small nucleolar RNA host gene 6 (SNHG6) is a long non-coding RNA (lncRNA) that has been widely implicated in cellular processes such as proliferation, migration, and differentiation. This study investigated its role in the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). qRT-PCR analysis revealed that SNHG6 expression increased during odontoblastic differentiation. In hDPSCs, SNHG6 was primarily localized in the cytoplasm. Functional studies using knockdown and overexpression demonstrated that SNHG6 positively regulates odontoblastic differentiation, as evidenced by alkaline phosphatase activity, Alizarin Red S staining, and the expression of differentiation markers DSPP and DMP-1. However, CCK-8 assays revealed SNHG6 had no significant impact on cell proliferation, and wound healing assays similarly showed it did not influence cell migration. Mechanistically, pathway inhibitors LY294002 and Rapamycin were used. Western blot analysis confirmed that SNHG6 promotes odontoblastic differentiation by activating the PI3K/Akt/mTOR signaling pathway, as shown by changes in phosphorylated Akt, mTOR, S6K1, and 4EBP1 levels. These findings highlight SNHG6 as a key regulator of hDPSC differentiation through PI3K/Akt/mTOR signaling, offering new insights into the molecular mechanisms controlling odontoblast formation.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"147 ","pages":"Article 100927"},"PeriodicalIF":2.6,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145738137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Gut and oral microbiota in oral bone tissue engineering: Impact of mechanistic and molecular pathways 口腔骨组织工程中的肠道和口腔微生物群：机制和分子途径的影响

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-12-02 DOI: 10.1016/j.diff.2025.100919

Khushi Gupta , Jiyaur Rahaman , Dhrubojyoti Mukherjee

The influence of the oral-gut microbiota on craniofacial bone healing is increasingly recognised, as its interactions with host osteoimmune pathways are now understood to shape the course of regeneration. These microbiota play an important role in maintaining bone mass via immune modulation, metabolite production, and nutrient resorption. Under conditions of dysbiosis, inflammatory signalling through NF-κB, NLRP3, and the RANKL/OPG axis is amplified, while Wnt/β-catenin and BMP/Smad pathways are suppressed, resulting in heightened oxidative stress, increased osteoclast activity, and progressive alveolar bone loss. In contrast, a balanced microbial community is associated with the production of short-chain fatty acids, through which epithelial barrier stability is supported, Th17/Treg equilibrium is restored, and osteoblast differentiation and mineralisation are promoted. In this review, mechanistic, preclinical, and emerging clinical evidence are integrated to illustrate how these microbial interactions regulate bone remodelling and influence the performance of engineered scaffolds. Therapeutic opportunities involving probiotics, prebiotics, synbiotics, engineered microbial strains, and microbiome-responsive biomaterials are emphasized. Cellular and molecular pathways controlling bone homeostasis, including the composition of the oral and gut microbiota, impacting oral bone health, have been summarized. Overall, the microbiome is positioned as a central biological determinant of oral bone regeneration, and its targeted modulation in addition to microbiome-based therapeutic strategies for bone tissue regeneration is proposed as a personalized approach for improving outcomes in craniofacial tissue engineering.

口腔肠道菌群对颅面骨愈合的影响越来越被认识到，因为它与宿主骨免疫途径的相互作用现在被理解为塑造再生过程。这些微生物群通过免疫调节、代谢物产生和营养物质吸收在维持骨量方面发挥重要作用。在生态失调的情况下，通过NF-κB、NLRP3和RANKL/OPG轴的炎症信号被放大，而Wnt/β-catenin和BMP/Smad通路被抑制，导致氧化应激升高，破骨细胞活性增加，牙槽骨逐渐丢失。相反，平衡的微生物群落与短链脂肪酸的产生有关，通过短链脂肪酸支持上皮屏障稳定性，恢复Th17/Treg平衡，促进成骨细胞分化和矿化。在这篇综述中，综合了机制，临床前和新出现的临床证据来说明这些微生物相互作用如何调节骨重塑和影响工程支架的性能。治疗机会涉及益生菌、益生元、合成菌、工程微生物菌株和微生物组响应生物材料被强调。本文综述了控制骨稳态的细胞和分子途径，包括口腔和肠道微生物群的组成，影响口腔骨骼健康。总体而言，微生物组被定位为口腔骨再生的核心生物学决定因素，除了基于微生物组的骨组织再生治疗策略外，其靶向调节被认为是改善颅面组织工程结果的个性化方法。

{"title":"Gut and oral microbiota in oral bone tissue engineering: Impact of mechanistic and molecular pathways","authors":"Khushi Gupta , Jiyaur Rahaman , Dhrubojyoti Mukherjee","doi":"10.1016/j.diff.2025.100919","DOIUrl":"10.1016/j.diff.2025.100919","url":null,"abstract":"<div><div>The influence of the oral-gut microbiota on craniofacial bone healing is increasingly recognised, as its interactions with host osteoimmune pathways are now understood to shape the course of regeneration. These microbiota play an important role in maintaining bone mass via immune modulation, metabolite production, and nutrient resorption. Under conditions of dysbiosis, inflammatory signalling through NF-κB, NLRP3, and the RANKL/OPG axis is amplified, while Wnt/β-catenin and BMP/Smad pathways are suppressed, resulting in heightened oxidative stress, increased osteoclast activity, and progressive alveolar bone loss. In contrast, a balanced microbial community is associated with the production of short-chain fatty acids, through which epithelial barrier stability is supported, Th17/Treg equilibrium is restored, and osteoblast differentiation and mineralisation are promoted. In this review, mechanistic, preclinical, and emerging clinical evidence are integrated to illustrate how these microbial interactions regulate bone remodelling and influence the performance of engineered scaffolds. Therapeutic opportunities involving probiotics, prebiotics, synbiotics, engineered microbial strains, and microbiome-responsive biomaterials are emphasized. Cellular and molecular pathways controlling bone homeostasis, including the composition of the oral and gut microbiota, impacting oral bone health, have been summarized. Overall, the microbiome is positioned as a central biological determinant of oral bone regeneration, and its targeted modulation in addition to microbiome-based therapeutic strategies for bone tissue regeneration is proposed as a personalized approach for improving outcomes in craniofacial tissue engineering.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"147 ","pages":"Article 100919"},"PeriodicalIF":2.6,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Dmxl1 is required for survival in the mouse to organogenesis stages of development Dmxl1是小鼠在器官发生发育阶段存活所必需的。

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-11-01 DOI: 10.1016/j.diff.2025.100917

Andrew M. Vontell , Logan Willeke , Paul P.R. Iyyanar , Rolf W. Stottmann

Cleft lip and cleft palate are among the most common congenital anomalies and are the result of incomplete fusion of embryonic craniofacial processes or palatal shelves. Genetic factors are known to play a large role in these anomalies, but the list of known causal genes is far from complete. As part of a larger effort to sequence patients with micrognathia and cleft palate, we identified candidate pathogenic variants in dmx-like 1 (DMXL1). We used genome editing to create an allelic series of Dmxl1 in the mouse: a small deletion and the two orthologous missense variants. We do not find evidence that either missense allele is pathogenic, but we do see that loss of Dmxl1 leads to very early embryonic lethality. This confirms and extends two recent findings about Dmxl1, suggesting this gene has crucial basal functions in the cell and should be further considered in human disease genetics.

唇裂和腭裂是最常见的先天性畸形之一，是胚胎颅面突或腭架不完全融合的结果。众所周知，遗传因素在这些异常中起着很大的作用，但已知的致病基因列表远未完整。作为对小颌畸形和腭裂患者进行测序的一部分，我们确定了dmx样1 （DMXL1）的候选致病变异。我们使用基因组编辑技术在小鼠中创建了Dmxl1等位基因系列：一个小缺失和两个同源错义变体。我们没有发现任何一个错义等位基因致病的证据，但我们确实看到Dmxl1的缺失会导致非常早期的胚胎死亡。这证实并扩展了最近关于Dmxl1的两项发现，表明该基因在细胞中具有关键的基础功能，应在人类疾病遗传学中进一步考虑。

引用次数: 0