Differentiation最新文献

{"title":"Direct Reciprocal Repression between Goosecoid and Ventx1.1 Modulates Dorsoventral Patterning in Xenopus","authors":"Basant Kumar,&nbsp;Zobia Umair,&nbsp;Seung-Hwan Lee,&nbsp;Unjoo Lee,&nbsp;Jaebong Kim","doi":"10.1016/j.diff.2026.100974","DOIUrl":"10.1016/j.diff.2026.100974","url":null,"abstract":"<div><div>Precise dorsoventral patterning in <em>Xenopus</em> embryos depends on coordinated transcriptional regulation between organizer and ventral genes. Goosecoid (Gsc) promotes dorsal identity, whereas Ventx1.1, a downstream effector of BMP signaling, specifies ventral fate. Although their antagonistic relationship has been described, the cis-regulatory basis underlying their reciprocal repression has not been clearly defined. Here, we demonstrate that Gsc and Ventx1.1 reciprocally repress each other's transcription through specific cis-regulatory elements within their promoters. Serial promoter deletions and site-directed mutagenesis identified a functional Goosecoid response element (GRE) in the <em>ventx1.1</em> promoter and Ventx1.1 response elements (VREs) in the <em>gsc</em> promoter. Mutation of these elements markedly reduced reciprocal repression in luciferase assays, and Chromatin immunoprecipitation revealed enrichment at the corresponding promoter regions during gastrulation. In addition, the neuroectoderm-specific transcription factor Foxd4l1.1 also repressed <em>gsc</em>, indicating an additional layer of transcriptional control that refines spatial gene expression. Together, these findings identify a promoter-level reciprocal repression circuit between Gsc and Ventx1.1 and suggest that this circuitry contributes to the refinement of dorsoventral patterning in <em>Xenopus</em> gastrulae.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"150 ","pages":"Article 100974"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266883","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}

{"title":"Ovarian fibrosis in polycystic ovary syndrome: Mechanisms, evidences, and clinical implications","authors":"Sakshi Nalkande,&nbsp;Mrudula Patil,&nbsp;Kartik Nakhate,&nbsp;Sameer Goyal","doi":"10.1016/j.diff.2026.100976","DOIUrl":"10.1016/j.diff.2026.100976","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a complex heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Emerging studies suggest that ovarian fibrosis, as an underrecognized pathological feature, may contribute to ovarian dysfunction and infertility in PCOS phenotypes. Available experimental and limited human studies indicate that hyperandrogenism, insulin resistance, chronic low-grade inflammation, oxidative and endoplasmic reticulum stress collectively promote extracellular matrix accumulation and stromal remodeling predominantly through transforming growth factor-β (TGF-β)-mediated signaling pathways. Additionally, fibrotic remodeling has been linked to other pathways, including the NLRP3 inflammasome, PI3K/Akt, Hippo/YAP, and epithelial-mesenchymal transition. Although standardised diagnostic criteria are currently lacking, new imaging modalities, such as shear-wave elastography, and circulating fibrosis-related biomarkers may offer non-invasive approaches to evaluating ovarian fibrotic alterations. Furthermore, several anti-fibrotic agents, metabolic modulators, phytochemicals, and stem cell-based therapies have been suggested to have potential therapeutic effects in ovarian fibrosis models of PCOS. Overall, ovarian fibrosis represents a developing aspect of PCOS pathophysiology that requires further clinical and translational investigation.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"150 ","pages":"Article 100976"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148406685","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}

{"title":"Palmatine enhances osteogenesis in hADMSCs via antioxidant enzyme upregulation and early RUNX2 activation","authors":"Tannaz Sakhavarz,&nbsp;Marzieh Ghollasi,&nbsp;Fereshteh Azedi,&nbsp;Nafiseh Abbasabadi","doi":"10.1016/j.diff.2026.100975","DOIUrl":"10.1016/j.diff.2026.100975","url":null,"abstract":"<div><div>Palmatine, a protoberberine alkaloid with recognized anti-inflammatory and anti-resorptive activities, has recently attracted interest as a potential modulator of bone homeostasis; however, its direct osteo-inductive effects on human adipose-derived mesenchymal stem cells (hADMSCs) remain undefined. Given the accessibility, proliferative efficiency, and clinical relevance of hADMSCs, identifying natural small molecules capable of enhancing their osteogenic differentiation is of considerable therapeutic significance. This study investigated the osteogenic potential of Palmatine using a multi-level <em>in vitro</em> approach. Cytotoxicity assays established a non-toxic working concentration. Osteogenic differentiation was assessed by quantifying alkaline phosphatase (ALP) activity, calcium deposition, and matrix mineralization using Alizarin Red and von Kossa staining. Mechanistic insight was gained by evaluating antioxidant enzyme activity (superoxide dismutase, catalase) and profiling key osteogenic genes via real-time RT-PCR. Low-dose Palmatine (1 μM) enhanced hADMSC viability, whereas higher concentrations displayed dose-dependent cytotoxicity. Functional assays demonstrated that Palmatine significantly increased ALP activity and calcium content at both early (Day 7) and late (Day 14) stages. Transcriptionally, Palmatine promoted early upregulation of Runt-related transcription factor 2, osteocalcin, and osteonectin, followed by robust induction of ALP and collagen type I at later stages, reflecting canonical osteogenic progression. Furthermore, Palmatine augmented antioxidant capacity through early elevation of superoxide dismutase and later activation of catalase, suggesting a redox-associated mechanism that stabilizes osteogenic signaling and supports matrix maturation. Overall, these findings provide the first comprehensive evidence that Palmatine functions as a potent, multi-level osteo-inductive molecule in hADMSCs, highlighting its promise as a natural candidate for redox-modulated bone regenerative strategies.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"150 ","pages":"Article 100975"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400029","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}

{"title":"Osteoclast-derived DEL1 promotes pathological bone formation in ankylosing spondylitis by regulating RUNX2 expression in osteoblasts","authors":"Seung Hoon Lee ,&nbsp;Chanhyeok Jeon ,&nbsp;Dongju Kim ,&nbsp;Hye-Ryeong Jo ,&nbsp;Eunae Ko ,&nbsp;Jeehee Youn ,&nbsp;Seunghun Lee ,&nbsp;Sung Hoon Choi ,&nbsp;Ye-Soo Park ,&nbsp;Sungsin Jo ,&nbsp;Tae-Hwan Kim","doi":"10.1016/j.diff.2026.100962","DOIUrl":"10.1016/j.diff.2026.100962","url":null,"abstract":"<div><h3>Background</h3><div>Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by ectopic bone formation. We investigated <em>in vitro</em> and <em>in vivo</em> the role of developmental endothelial locus-1 (DEL1) on new bone formation and determined the association between DEL1 and spinal progression in AS.</div></div><div><h3>Methods</h3><div>DEL1 levels were measured in plasma and facet joint tissues from patients with AS, and in osteoclast-derived medium. Human osteoblast precursor cells were treated with recombinant DEL1 protein and cilengitide trifluoroacetate, an αvβ3 integrin inhibitor, to evaluate their effects on osteoblast differentiation markers. A curdlan-injected SKG mouse model was used to mimic AS pathogenesis. Three weeks after curdlan injection, recombinant DEL1 protein or cilengitide was administered, and the mice's ankle thickness was assessed. The mice were sacrificed after six weeks, and micro-CT and histological analyses were performed.</div></div><div><h3>Results</h3><div>DEL1 expression significantly increased during osteoclast differentiation, peaked at the terminal stage, and correlated with disease progression in AS mice. Systemic plasma DEL1 levels were not different between patients with AS and the control group, but were positively correlated with structural damage (mSASSS; R = 0.3433, p = 0.0195). DEL1 pro-osteogenic effects were neutralized by cilengitide, which attenuated DEL1-induced RUNX2 expression and matrix mineralization.</div></div><div><h3>Conclusion</h3><div>Our findings establish DEL1 as a key osteoclast-derived coupling factor that drives new bone formation in AS. DEL1 promotes pathological bone formation and osteoblast differentiation by signaling through the integrin αVβ3-RUNX2 axis; targeting this pathway may offer a novel approach to prevent structural damage in patients with AS.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"149 ","pages":"Article 100962"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147935273","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}

{"title":"Bridging cells: Potential crosstalk between the peripheral and central olfactory sensory system","authors":"Jorge Torres-Paz ,&nbsp;Ricardo Ceriani ,&nbsp;Kathleen E. Whitlock","doi":"10.1016/j.diff.2026.100961","DOIUrl":"10.1016/j.diff.2026.100961","url":null,"abstract":"<div><div>The olfactory sensory system in unique is that the first synaptic contact lies within the central nervous system meaning that the same olfactory sensory neuron whose dendrites are in contact with outside world, has axons extending directly into the central nervous system. Furthermore, neurons of both the peripheral olfactory organ and central olfactory bulb undergo neurogenesis throughout life, although it is unknown whether this is a coordinated process. Here we describe a group of cells in the adult olfactory epithelia that are neuron-like in appearance, yet express the oligodendrocyte precursor marker Olig2:EGFP<em>.</em> These cells extend processes that bypass the olfactory bulbs to arrive at the anterior telencephalic ventricle, the site of precursors that produce interneurons of the olfactory bulbs via the rostral migratory stream. Characterization in sections from intact, wholemount adult brains revealed Sox10 positive cells in patterns consistent with potential migration between the olfactory epithelia and the olfactory bulbs. Based on the expression of Sox10 protein, these cells are assumed to be olfactory ensheathing cells that populate the peripheral and central olfactory system. These cells are a unique type of “hybrid” glia expressing markers associated with astrocytes, oligodendrocytes, and microglia, as well as with progenitor characteristics. Thus, the Olig2:EGFP positive cells link the peripheral olfactory epithelia with the anterior telencephalic vesicle, the source of rostral migratory stream progenitors. These cells provide a potential link to the Sox10+ olfactory ensheathing cells in the adult brain shown here, thus supporting previous findings showing that olfactory ensheathing cells can exert an attractive influence on neuronal migration within the rostral migratory stream.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"149 ","pages":"Article 100961"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148058040","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}

{"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 ,&nbsp;Kyle Drover ,&nbsp;Anton Shpak ,&nbsp;Neil R. Horner ,&nbsp;Victoria O'Reilly ,&nbsp;Emma Cocking ,&nbsp;Joelene A. Greasby ,&nbsp;Kavitha R. Iyer ,&nbsp;Ruth Arkell ,&nbsp;Sally L. Dunwoodie ,&nbsp;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":"2026-03-01","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}

{"title":"Low and high osteogenic potential of periodontal ligament-derived mesenchymal stem cells correlates with RUNX2, SP7, EZH2 and KDM6B expression","authors":"D.C. Andia ,&nbsp;L.F. Oliveira ,&nbsp;G.S. Feltran ,&nbsp;A.A.S. Gonçalves ,&nbsp;W.F. Zambuzzi ,&nbsp;R.A. da Silva","doi":"10.1016/j.diff.2026.100944","DOIUrl":"10.1016/j.diff.2026.100944","url":null,"abstract":"<div><div>Periodontal ligament-derived mesenchymal stem cells (PDLCs) possess selfrenewal and multilineage differentiation capacities, supporting their application in regenerative therapies. However, PDLCs are regulated by epigenetic mechanisms that influence chromatin accessibility and gene expression, and may exhibit distinct phenotypes under osteogenic conditions. This study aimed to investigate whether differences in osteogenic potential of PDLCs (h-PDLCs and l-PDLCs, high and low, respectively) correlate with the expression of key transcription factors and epigenetic regulators. We performed qPCR for mRNA expression analysis, immunofluorescence, and Western blotting for protein levels, as well as chromatin immunoprecipitation followed by qRT-PCR to investigate H3K27me3 enrichment at the <em>RUNX2</em> and <em>SP7</em> promoter regions in PDLCs cultured under basal conditions (DMEM, T0) and after 3 and 10 days of osteogenic induction (T3 and T10). At baseline, h-PDLCs and l-PDLCs exhibited distinct transcriptional and protein profiles. During osteogenic stimulation, <em>EZH2</em> expression significantly increased in l-PDLCs but decreased in h-PDLCs (<em>p</em> &lt; 0.001), while <em>KDM6B</em> expression decreased in l-PDLCs and increased in hPDLCs (<em>p</em> &lt; 0.0001). Analysis of <em>RUNX2</em>, <em>RUNX2p57</em>, and <em>SP7</em> revealed dynamic transcriptional modulation: <em>RUNX2p57</em> and <em>SP7</em> were downregulated in l-PDLCs (<em>p</em> &lt; 0,001), whereas <em>RUNX2</em> was upregulated in h-PDLCs (T3 and T10, <em>p</em> &lt; 0,0001). Furthermore, l-PDLCs exhibited greater accumulation of the repressive histone mark H3K27me3, with significant enrichment at the <em>RUNX2</em> and <em>SP7</em> promoter regions compared to h-PDLCs during osteogenic induction (<em>p</em> &lt; 0.05). Together, these findings demonstrate that low and high osteogenic potential of PDLCs correlate with coordinated differences in the expression of the transcription factors RUNX2 and SP7 and the epigenetic regulators EZH2 and KDM6B, as well as with H3K27me3 enrichment patterns.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"148 ","pages":"Article 100944"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146191391","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}

{"title":"Ex vivo human cellular models to study adipocyte-induced transdifferentiation of osteoblasts","authors":"Federica Quacquarelli ,&nbsp;Damien Leterme ,&nbsp;Véronique Gauthier ,&nbsp;Jérôme Delattre ,&nbsp;Paiva dos Santos Bruno ,&nbsp;Emeline Cailliau ,&nbsp;Eric Fodzo ,&nbsp;Antonella Poloni ,&nbsp;Aline Clabaut ,&nbsp;Odile Broux","doi":"10.1016/j.diff.2026.100947","DOIUrl":"10.1016/j.diff.2026.100947","url":null,"abstract":"<div><div>In human, an association between bone loss and increased marrow adipose tissue suggests that medullary adipocytes could play a role in osteoporosis by acting on neighboring bone-forming osteoblasts. Supporting this hypothesis, we previously showed, using coculture and conditioned medium models based on human bone marrow stromal cells of commercial origin, that factors secreted by adipocytes induced the transdifferentiation of osteoblasts towards an adipocyte-like phenotype.</div><div>The aim of this study was to confirm the involvement of medullary adipocyte secretion products in the alteration of osteoblasts in pathophysiological conditions. To this end, two new cellular models were developed from human bone biopsies representing the aging skeleton. In the first model, outgrowth from trabecular bone fragments were used to isolate primary cells that displayed a specific osteoblast phenotype. We confirmed the transdifferentiation of these primary osteoblasts following their incubation with adipocyte conditioned medium as evidenced by the increase in the levels of adipogenic mRNA markers (PPARG, Leptin and HSD11B1, P &lt; 0,001) and the decrease of osteogenic transcript (BGLAP, P &lt; 0.05). The second model was based on primary adipocyte isolation through collagenase treatment followed by ceiling and 2D culture. Oil red O staining confirmed the isolation of fully-differentiated primary adipocytes from bone biopsies. Experiments performed with their conditioned medium validated what had been observed with primary osteoblasts: the effect of the adipocyte secretome on osteoblast fate. Overall, our results supported the relevance of these models to examine paracrine interactions between osteoblasts and adipocytes and confirmed the role played by adipocyte-secreted factors in osteoblast transdifferentiation.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"148 ","pages":"Article 100947"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167793","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}

{"title":"Development and proteome characterization of a new muscle cell line from Oreochromis niloticus (Linnaeus, 1758)","authors":"Vijay Lakshmi Sahoo,&nbsp;A. Sathiyanarayanan,&nbsp;Nevil Pinto,&nbsp;Gowhar Iqbal,&nbsp;B.S. Yashwanth,&nbsp;Arvind A. Sonwane,&nbsp;Kiran D. Rasal,&nbsp;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}

{"title":"Her9 is required for the migration, differentiation, and survival of neural crest cells","authors":"Cagney E. Coomer ,&nbsp;Sumanth Manohar ,&nbsp;Evelyn M. Turnbaugh ,&nbsp;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}