Differentiation最新文献

{"title":"Fibroblast growth factors-An introduction to our primer series","authors":"Jennifer L. Fish","doi":"10.1016/j.diff.2024.100804","DOIUrl":"10.1016/j.diff.2024.100804","url":null,"abstract":"","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100804"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908208","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":"The fundamentals of fibroblast growth factor 9","authors":"","doi":"10.1016/j.diff.2023.09.004","DOIUrl":"10.1016/j.diff.2023.09.004","url":null,"abstract":"<div><p>Fibroblast growth factor 9 (FGF9) was first identified during a screen for factors acting on cells of the central nervous system (CNS). Research over the subsequent two decades has revealed this protein to be a critically important and elegantly regulated growth factor. A hallmark control feature is reciprocal compartmentalization, particularly during development, with epithelium as a dominant source and mesenchyme a prime target. This mesenchyme selectivity is accomplished by the high affinity of FGF9 to the IIIc isoforms of FGFR1, 2, and 3. FGF9 is expressed widely in the embryo, including the developing heart and lungs, and more selectively in the adult, including the CNS and kidneys. Global <em>Fgf9</em>-null mice die shortly after birth due to respiratory failure from hypoplastic lungs. As well, their hearts are dilated and poorly vascularized, the skeleton is small, the intestine is shortened, and male-to-female sex reversal can be found. Conditional <em>Fgf9</em>-null mice have revealed CNS phenotypes, including ataxia and epilepsy. In humans, FGF9 variants have been found to underlie multiple synostoses syndrome 3, a syndrome characterized by multiple joint fusions. Aberrant FGF9 signaling has also been implicated in differences of sex development and cancer, whereas vascular stabilizing effects of FGF9 could benefit chronic diseases. This primer reviews the attributes of this vital growth factor.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100731"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468123000701/pdfft?md5=23f4eeadf978eaf63e5001caf117f167&pid=1-s2.0-S0301468123000701-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41168409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGF1","authors":"Sahar B. Jamal ,&nbsp;Dorit Hockman","doi":"10.1016/j.diff.2024.100802","DOIUrl":"10.1016/j.diff.2024.100802","url":null,"abstract":"<div><p>Fibroblast Growth Factor 1 (Fgf1), also known as acidic FGF (aFGF), is involved in the regulation of various biological processes, ranging from development to disease pathogenesis. It is a single chain polypeptide and is highly expressed in adult brain and kidney tissues. Its expression has been shown to be directed by multiple tissue-specific promoters, which generate transcripts of varying lengths. During development the <em>Fgf1</em> gene is widely expressed, including in the neural tube, heart and lung. Mouse mutants for this gene are normal under standard laboratory conditions. However, when <em>Fgf1</em> mutants are exposed to a high fat diet, an aggressive diabetic phenotype has been reported, along with aberrant adipose tissue expansion. Ongoing research on FGF1 and its signalling pathways holds promise for greater understanding of developmental processes as well as the development of novel therapeutic interventions for diseases including diabetes.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100802"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468124000586/pdfft?md5=b5185e6e036ec7666f2f99ad5a6845f6&pid=1-s2.0-S0301468124000586-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primer on FGF3","authors":"","doi":"10.1016/j.diff.2023.09.003","DOIUrl":"10.1016/j.diff.2023.09.003","url":null,"abstract":"<div><p><span>Though initially discovered as a proto-oncogene in virally induced mouse mammary tumors, FGF3<span> is primarily active in prenatal stages, where it is found at various sites at specific times. FGF3 is crucial during development, as its roles include tail formation, inner ear development and hindbrain induction and patterning. FGF3 expression and function are highly conserved in vertebrates, while it also interacts with other FGFs in various developmental processes. Intriguingly, while it is classified as a classical </span></span>paracrine signaling<span> factor, murine FGF3 was uniquely found to also act in an intracrine<span> manner, depending on alternative translation initiation sites. Corresponding with its conserved role in inner ear morphogenesis, mutations in FGF3 in humans are associated with LAMM syndrome, a disorder that include hearing loss and inner ear malformations. While recent studies indicate of some FGF3 presence in post-natal stages, emerging evidences of its upregulation in various human tumors and cariogenic processes in mouse models, highlights the importance of its close regulation in adult tissues. Altogether, the broad and dynamic expression pattern and regulation of FGF3 in embryonic and adult tissues together with its link to congenital malformations and cancer, calls for further discoveries of its diverse roles in health and disease.</span></span></p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100730"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41177346","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":"Reprint of: Fibroblast Growth Factor 6","authors":"Jennelle Smith ,&nbsp;Loydie A. Jerome-Majewska","doi":"10.1016/j.diff.2024.100805","DOIUrl":"10.1016/j.diff.2024.100805","url":null,"abstract":"<div><p>Fibroblast Growth Factor 6 (<em>FGF6</em>), also referred to as <em>HST2</em> or <em>HBGF6</em>, is a member of the Fibroblast Growth Factor (FGF), the Heparin Binding Growth Factor (HBGF) and the Heparin Binding Secretory Transforming Gene (HST) families. The genomic and protein structure of FGF6 is highly conserved among varied species, as is its expression in muscle and muscle progenitor cells. Like other members of the FGF family, <em>FGF6</em> regulates cell proliferation, differentiation, and migration. Specifically, it plays key roles in myogenesis and muscular regeneration, angiogenesis, along with iron transport and lipid metabolism. Similar to others from the FGF family, <em>FGF6</em> also possesses oncogenic transforming activity, and as such is implicated in a variety of cancers.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100805"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468124000616/pdfft?md5=dee6892444749fc6445e758bdfdef49e&pid=1-s2.0-S0301468124000616-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast growth factor 2","authors":"","doi":"10.1016/j.diff.2023.10.001","DOIUrl":"10.1016/j.diff.2023.10.001","url":null,"abstract":"<div><p><span>Fibroblast Growth Factor 2<span><span> (FGF2), also known as basic fibroblast growth factor, is a potent stimulator of growth and differentiation in multiple tissues. Its discovery traces back over 50 years ago when it was first isolated from bovine pituitary extracts due to its ability to stimulate fibroblast proliferation. Subsequent studies investigating the </span>genomic structure of </span></span><em>FGF2</em><span><span> identified multiple protein isoforms<span>, categorized as the low molecular weight and high molecular weight FGF2. These isoforms arise from alternative translation initiation events and exhibit unique molecular and cellular functions. In this concise review, we aim to provide an overview of what is currently known about the structure, expression, and functions of the FGF2 isoforms within the contexts of development, </span></span>homeostasis, and disease.</span></p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"139 ","pages":"Article 100733"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684537","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":"Lens placode modulates extracellular matrix formation during early eye development","authors":"Cecília G. De Magalhães ,&nbsp;Ales Cvekl ,&nbsp;Ruy G. Jaeger ,&nbsp;C.Y. Irene Yan","doi":"10.1016/j.diff.2024.100792","DOIUrl":"10.1016/j.diff.2024.100792","url":null,"abstract":"<div><p>The role extracellular matrix (ECM) in multiple events of morphogenesis has been well described, little is known about its specific role in early eye development. One of the first morphogenic events in lens development is placodal thickening, which converts the presumptive lens ectoderm from cuboidal to pseudostratified epithelium. This process occurs in the anterior pre-placodal ectoderm when the optic vesicle approaches the cephalic ectoderm and is regulated by transcription factor Pax6 and secreted BMP4. Since cells and ECM have a dynamic relationship of interdependence and modulation, we hypothesized that the ECM evolves with cell shape changes during lens placode formation. This study investigates changes in optic ECM including both protein distribution deposition, extracellular gelatinase activity and gene expression patterns during early optic development using chicken and mouse models. In particular, the expression of <em>Timp2</em>, a metalloprotease inhibitor, corresponds with a decrease in gelatinase activity within the optic ECM. Furthermore, we demonstrate that optic ECM remodeling depends on BMP signaling in the placode. Together, our findings suggest that the lens placode plays an active role in remodeling the optic ECM during early eye development.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"138 ","pages":"Article 100792"},"PeriodicalIF":2.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472143","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":"Generation of a Wt1 conditional deletion, nuclear red fluorescent protein reporter allele in the mouse","authors":"Jace A. Aloway ,&nbsp;E. Cristy Ruteshouser ,&nbsp;Vicki Huff ,&nbsp;Richard R. Behringer","doi":"10.1016/j.diff.2024.100791","DOIUrl":"10.1016/j.diff.2024.100791","url":null,"abstract":"<div><p>A <em>Wt1</em> conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a <em>Wt1</em>-specific pattern. RFP expression was detected in embryonic and adult tissues known to express <em>Wt1</em>, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with <em>Wnt7a-Cre</em> transgenic mice that express <em>Cre</em> in the Müllerian duct epithelium activate <em>Wt1</em>-directed RFP expression in the epithelium of the oviduct but not the stroma and myometrium of the uterus. This new mouse strain should be a useful resource for studies of <em>Wt1</em> function and marking <em>Wt1</em>-expressing cells.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"138 ","pages":"Article 100791"},"PeriodicalIF":2.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472142","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":"Characterization of the zebrafish gabra1sa43718/sa43718 germline loss of function allele confirms a function for Gabra1 in motility and nervous system development","authors":"Nayeli G. Reyes-Nava ,&nbsp;David Paz ,&nbsp;Briana E. Pinales,&nbsp;Isaiah Perez,&nbsp;Claudia B. Gil,&nbsp;Annalise V. Gonzales,&nbsp;Brian I. Grajeda ,&nbsp;Igor L. Estevao ,&nbsp;Cameron C. Ellis ,&nbsp;Victoria L. Castro,&nbsp;Anita M. Quintana","doi":"10.1016/j.diff.2024.100790","DOIUrl":"10.1016/j.diff.2024.100790","url":null,"abstract":"<div><p>Mutation of the <em>GABRA1</em> gene is associated with neurodevelopmental defects and epilepsy. <em>GABRA1</em> encodes for the α1 subunit of the γ-aminobutyric acid type A receptor (GABA_AR), which regulates the fast inhibitory impulses of the nervous system. Multiple model systems have been developed to understand the function of <em>GABRA1</em>, but these models have produced complex and, at times, incongruent data. Thus, additional model systems are required to validate and substantiate previous results. We sought to provide initial phenotypic analysis of a novel germline mutant allele. Our analysis provides a solid foundation for the future use of this allele to characterize <em>gabra1</em> functionally and pharmacologically using zebrafish. We investigated the behavioral swim patterns associated with a nonsense mutation of the zebrafish <em>gabra1</em> (<em>sa43718</em> allele) gene. The <em>sa43718</em> allele causes a decrease in <em>gabra1</em> mRNA expression, which is associated with light induced hypermotility, one phenotype previously associated with seizure like behavior in zebrafish. Mutation of <em>gabra1</em> was accompanied by decreased mRNA expression of <em>gabra2, gabra3, and gabra5,</em> indicating a reduction in the expression of additional α sub-units of the GABA_AR. Although multiple sub-units were decreased, larvae continued to respond to pentylenetetrazole (PTZ), indicating that a residual GABA_AR exists in the <em>sa43718</em> allele. Proteomics analysis demonstrated that mutation of <em>gabra1</em> is associated with abnormal expression of proteins that regulate synaptic vesicle fusion, vesicle transport, synapse development, and mitochondrial protein complexes. These data support previous studies performed in a zebrafish nonsense allele created by CRISPR/Cas9 and validate that loss of function mutations in the <em>gabra1</em> gene result in seizure-like phenotypes with abnormal development of the GABA synapse. Our results add to the existing body of knowledge as to the function of GABRA1 during development and validate that zebrafish can be used to provide complete functional characterization of the gene.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"138 ","pages":"Article 100790"},"PeriodicalIF":2.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141407482","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":"Exploring the impact of osteoprotegerin on osteoclast and precursor fusion: Mechanisms and modulation by ATP","authors":"Yunwen Peng ,&nbsp;Hongyan Zhao ,&nbsp;Sinan Hu ,&nbsp;Yonggang Ma ,&nbsp;Tao Han ,&nbsp;Chuang Meng ,&nbsp;Xishuai Tong ,&nbsp;Hui Zou ,&nbsp;Zongping Liu ,&nbsp;Ruilong Song","doi":"10.1016/j.diff.2024.100789","DOIUrl":"10.1016/j.diff.2024.100789","url":null,"abstract":"<div><p>Osteoclast (OC) differentiation, vital for bone resorption, depends on osteoclast and precursor fusion. Osteoprotegerin (OPG) inhibits osteoclast differentiation. OPG's influence on fusion and mechanisms is unclear. Osteoclasts and precursors were treated with OPG alone or with ATP. OPG significantly reduced OC number, area and motility and ATP mitigated OPG's inhibition. However, OPG hardly affected the motility of precusors. OPG downregulated fusion-related molecules (CD44, CD47, DC-STAMP, ATP6V0D2) in osteoclasts, reducing only CD47 in precursors. OPG reduced Connexin43 phosphorylated forms (P1 and P2) in osteoclasts, affecting only P2 in precursors. OPG disrupted subcellular localization of CD44, CD47, DC-STAMP, ATP6V0D2, and Connexin43 in both cell types. Findings underscore OPG's multifaceted impact, inhibiting multinucleated osteoclast and mononuclear precursor fusion through distinct molecular mechanisms. Notably, ATP mitigates OPG's inhibitory effect, suggesting a potential regulatory role for the ATP signaling pathway. This study enhances understanding of intricate processes in osteoclast differentiation and fusion, offering insights into potential therapeutic targets for abnormal bone metabolism.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"138 ","pages":"Article 100789"},"PeriodicalIF":2.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141393992","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}