Developmental Dynamics最新文献

{"title":"Enigmatic Nodal and Lefty gene repertoire discrepancy: Latent evolutionary history revealed by vertebrate‐wide phylogeny","authors":"Shigehiro Kuraku","doi":"10.1002/dvdy.710","DOIUrl":"https://doi.org/10.1002/dvdy.710","url":null,"abstract":"Homology in vertebrate body plans is traditionally ascribed to the high‐level conservation of regulatory components within the genetic programs governing them, particularly during the “phylotypic stage.” However, advancements in embryology and molecular phylogeny have unveiled the dynamic nature of gene repertoires responsible for early development. Notably, the <jats:italic>Nodal</jats:italic> and <jats:italic>Lefty</jats:italic> genes, members of the transforming growth factor‐beta superfamily producing intercellular signaling molecules and crucial for left–right (L‐R) symmetry breaking, exhibit distinctive features within their gene repertoires. These features encompass among‐species gene repertoire variations resulting from gene gain and loss, as well as gene conversion. Despite their significance, these features have been largely unexplored in a phylogenetic context, but accumulating genome‐wide sequence information is allowing the scrutiny of these features. It has exposed hidden paralogy between <jats:italic>Nodal1</jats:italic> and <jats:italic>Nodal2</jats:italic> genes resulting from differential gene loss in amniotes. In parallel, the tandem cluster of <jats:italic>Lefty1</jats:italic> and <jats:italic>Lefty2</jats:italic> genes, which was thought to be confined to mammals, is observed in sharks and rays, with an unexpected phylogenetic pattern. This article provides a comprehensive review of the current understanding of the origins of these vertebrate gene repertoires and proposes a revised nomenclature based on the elucidated history of vertebrate genome evolution.","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"38 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635653","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":"Editorial highlights","authors":"Paul A. Trainor","doi":"10.1002/dvdy.709","DOIUrl":"https://doi.org/10.1002/dvdy.709","url":null,"abstract":"&lt;p&gt;Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in &lt;i&gt;Developmental Dynamics&lt;/i&gt; that illustrate the complex dynamics of developmental biology.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Sensory Development&lt;/b&gt;. “Rspo1 and Rspo3 are required for sensory lineage neural crest formation in mouse embryos” by Takuma Shinozuka, Motoko Aoki, Yudai Hatakeyama, Noriaki Sasai, Hiroshi Okamoto, and Shinji Takada; &lt;i&gt;Dev Dyn&lt;/i&gt; 253:4, pp. 435–446. https://doi.org/10.1002/dvdy.659. Wnt/β-catenin signaling plays multiple critical roles during embryonic development and throughout adult homeostasis, and R-spondins (Rspos) are secreted proteins that modulate Wnt/β-catenin signaling. This study documented the expression of all four &lt;i&gt;Rspo&lt;/i&gt; genes in the developing mouse spinal cord and found that &lt;i&gt;Rspo1&lt;/i&gt; and &lt;i&gt;Rspo3&lt;/i&gt; are specifically expressed in the roof plate from E9.5 to E18.5. To functionally test for the roles of &lt;i&gt;Rspo1&lt;/i&gt; and &lt;i&gt;Rspo3&lt;/i&gt; in the developing spinal cord, the authors generated mutant embryos defective in either or both of these Rspos. &lt;i&gt;Rspo1&lt;/i&gt;-KO and &lt;i&gt;Rspo3&lt;/i&gt;-cKO double-mutant embryos displayed defects in specification of Ngn2-positive sensory lineage cells. The results show that although &lt;i&gt;Rspo1&lt;/i&gt; and &lt;i&gt;Rspo3&lt;/i&gt; are dispensable for most developmental processes involving roof plate-derived Wnt ligands, they are critically required for specification of a subtype of neural crest cells. Thus, Rspos modulate Wnt/β-catenin signaling in a context-dependent manner.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Axial Development and Elongation&lt;/b&gt;. “Specific CaMKIIs mediate convergent extension cell movements in early zebrafish development” by Jamie McLeod, Sarah Rothschild, Ludmila Francescatto, Haerin Kim, and Robert Tombes; &lt;i&gt;Dev Dyn&lt;/i&gt; 253:4, pp. 390–403. https://doi.org/10.1002/dvdy.665. Coordinated inductive and morphogenetic processes establish the vertebrate body plan during gastrulation. Central to this process is convergent extension which narrows the germ layers mediolaterally (convergence) while elongating them anterioposteriorly (extension). Non-canonical Wnts are morphogens that can elevate intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; and activate the Ca&lt;sup&gt;2+&lt;/sup&gt;/calmodulin-dependent protein kinase, CaMKII, and promote convergent extension cell movements during vertebrate gastrulation. In this study, the authors demonstrate that zebrafish embryos spatiotemporally express seven CaMKII genes during embryogenesis, two of which camk2b1 and camk2g1, are necessary for convergent extension cell movements. Interestingly, overexpression of CaMKII partially rescued Wnt11 morphant convergent extension phenotypes. Therefore, cyclically activated CaMKII encoded from two genes enables cell migration during the proc","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 4","pages":"368-369"},"PeriodicalIF":2.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140333184","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":"Reduced mTORC1-signaling in progenitor cells leads to retinal lamination deficits","authors":"Christoffer Nord,&nbsp;Iwan Jones,&nbsp;Maria Garcia-Maestre,&nbsp;Anna-Carin Hägglund,&nbsp;Leif Carlsson","doi":"10.1002/dvdy.707","DOIUrl":"10.1002/dvdy.707","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuronal lamination is a hallmark of the mammalian central nervous system (CNS) and underlies connectivity and function. Initial formation of this tissue architecture involves the integration of various signaling pathways that regulate the differentiation and migration of neural progenitor cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we demonstrate that mTORC1 mediates critical roles during neuronal lamination using the mouse retina as a model system. Down-regulation of mTORC1-signaling in retinal progenitor cells by conditional deletion of <i>Rptor</i> led to decreases in proliferation and increased apoptosis during embryogenesis. These developmental deficits preceded aberrant lamination in adult animals which was best exemplified by the fusion of the outer and inner nuclear layer and the absence of an outer plexiform layer. Moreover, ganglion cell axons originating from each <i>Rptor</i>-ablated retina appeared to segregate to an equal degree at the optic chiasm with both contralateral and ipsilateral projections displaying overlapping termination topographies within several retinorecipient nuclei. In combination, these visual pathway defects led to visually mediated behavioral deficits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study establishes a critical role for mTORC1-signaling during retinal lamination and demonstrates that this pathway regulates diverse developmental mechanisms involved in driving the stratified arrangement of neurons during CNS development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 10","pages":"922-939"},"PeriodicalIF":2.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.707","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305199","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":"Deciphering adipose development: Function, differentiation and regulation","authors":"Ge Guo,&nbsp;Wanli Wang,&nbsp;Mengjie Tu,&nbsp;Binbin Zhao,&nbsp;Jiayang Han,&nbsp;Jiali Li,&nbsp;Yanbing Pan,&nbsp;Jie Zhou,&nbsp;Wen Ma,&nbsp;Yi Liu,&nbsp;Tiantian Sun,&nbsp;Xu Han,&nbsp;Yang An","doi":"10.1002/dvdy.708","DOIUrl":"10.1002/dvdy.708","url":null,"abstract":"<p>The overdevelopment of adipose tissues, accompanied by excess lipid accumulation and energy storage, leads to adipose deposition and obesity. With the increasing incidence of obesity in recent years, obesity is becoming a major risk factor for human health, causing various relevant diseases (including hypertension, diabetes, osteoarthritis and cancers). Therefore, it is of significance to antagonize obesity to reduce the risk of obesity-related diseases. Excess lipid accumulation in adipose tissues is mediated by adipocyte hypertrophy (expansion of pre-existing adipocytes) or hyperplasia (increase of newly-formed adipocytes). It is necessary to prevent excessive accumulation of adipose tissues by controlling adipose development. Adipogenesis is exquisitely regulated by many factors in vivo and in vitro, including hormones, cytokines, gender and dietary components. The present review has concluded a comprehensive understanding of adipose development including its origin, classification, distribution, function, differentiation and molecular mechanisms underlying adipogenesis, which may provide potential therapeutic strategies for harnessing obesity without impairing adipose tissue function.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 11","pages":"956-997"},"PeriodicalIF":2.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184019","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":"Disruption of Fuz in mouse embryos generates hypoplastic hindbrain development and reduced cranial nerve ganglia","authors":"Carlo Donato Caiaffa,&nbsp;Yogeshwari S. Ambekar,&nbsp;Manmohan Singh,&nbsp;Ying Linda Lin,&nbsp;Bogdan Wlodarczyk,&nbsp;Salavat R. Aglyamov,&nbsp;Giuliano Scarcelli,&nbsp;Kirill V. Larin,&nbsp;Richard H. Finnell","doi":"10.1002/dvdy.702","DOIUrl":"10.1002/dvdy.702","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The brain and spinal cord formation is initiated in the earliest stages of mammalian pregnancy in a highly organized process known as neurulation. Environmental or genetic interferences can impair neurulation, resulting in clinically significant birth defects known collectively as neural tube defects. The <i>Fuz</i> gene encodes a subunit of the CPLANE complex, a macromolecular planar polarity effector required for ciliogenesis. Ablation of <i>Fuz</i> in mouse embryos results in exencephaly and spina bifida, including dysmorphic craniofacial structures due to defective cilia formation and impaired Sonic Hedgehog signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that knocking <i>Fuz</i> out during embryonic mouse development results in a hypoplastic hindbrain phenotype, displaying abnormal rhombomeres with reduced length and width. This phenotype is associated with persistent reduction of ventral neuroepithelial stiffness in a notochord adjacent area at the level of the rhombomere 5. The formation of cranial and paravertebral ganglia is also impaired in these embryos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study reveals that hypoplastic hindbrain development, identified by abnormal rhombomere morphology and persistent loss of ventral neuroepithelial stiffness, precedes exencephaly in <i>Fuz</i> ablated murine mutants, indicating that the gene <i>Fuz</i> has a critical function sustaining normal neural tube development and neuronal differentiation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 9","pages":"846-858"},"PeriodicalIF":2.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157811","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":"Gap junctions in polycystic ovary syndrome: Implications for follicular arrest","authors":"Ying Zhu,&nbsp;Hongqiu Zhu,&nbsp;Peijuan Wu","doi":"10.1002/dvdy.706","DOIUrl":"10.1002/dvdy.706","url":null,"abstract":"<p>Gap junctions are specialized intercellular conduits that provide a direct pathway between neighboring cells, which are involved in numerous physiological processes, such as cellular differentiation, cell growth, and metabolic coordination. The effect of gap junctional hemichannels in folliculogenesis is particularly obvious, and the down-regulation of connexins is related to abnormal follicle growth. Polycystic ovary syndrome (PCOS) is a ubiquitous endocrine disorder of the reproductive system, affecting the fertility of adult women due to anovulation. Exciting evidence shows that gap junction is involved in the pathological process related to PCOS and affects the development of follicles in women with PCOS. In this review, we examine the expression of connexins in follicular cells of PCOS and figure out whether such communication could have consequences for PCOS women. While along with results from clinical and related animal studies, we summarize the mechanism of connexins involved in the pathogenesis of PCOS.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 10","pages":"882-894"},"PeriodicalIF":2.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157812","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":"Protein signaling and morphological development of the tail fluke in the embryonic beluga whale (Delphinapterus leucas)","authors":"L. M. Gavazzi,&nbsp;M. Nair,&nbsp;R. Suydam,&nbsp;S. Usip,&nbsp;J. G. M. Thewissen,&nbsp;L. N. Cooper","doi":"10.1002/dvdy.704","DOIUrl":"10.1002/dvdy.704","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>During the land-to-sea transition of cetaceans (whales, dolphins, and porpoises), the hindlimbs were lost and replaced by an elaborate tail fluke that evolved 32 Ma. All modern cetaceans utilize flukes for lift-based propulsion, and nothing is known of this organ's molecular origins during embryonic development. This study utilizes immunohistochemistry to identify the spatiotemporal location of protein signals known to drive appendage outgrowth in other vertebrates (e.g., Sonic Hedgehog [SHH], GREMLIN [GREM], wingless-type family member 7a [WNT], and fibroblast growth factors [FGFs]) and to test the hypothesis that signals associated with outgrowth and patterning of the tail fluke are similar to a tetrapod limb. Specifically, this study utilizes an embryo of a beluga whale (<i>Delphinapterus leucas</i>) as a case study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Results showed epidermal signals of WNT and FGFs, and mesenchymal/epidermal signals of SHH and GREM. These patterns are most consistent with vertebrate limb development. Overall, these data are most consistent with the hypothesis that outgrowth of tail flukes in cetaceans employs a signaling pattern that suggests genes essential for limb outgrowth and patterning shape this evolutionarily novel appendage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>While these data add insights into the molecular signals potentially driving the evolution and development of tail flukes in cetaceans, further exploration of the molecular drivers of fluke development is required.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 9","pages":"859-874"},"PeriodicalIF":2.0,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142993","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":"Lineage-specific requirements of Alx4 function in craniofacial and hair development","authors":"Yu Lan,&nbsp;Zhaoming Wu,&nbsp;Han Liu,&nbsp;Rulang Jiang","doi":"10.1002/dvdy.705","DOIUrl":"10.1002/dvdy.705","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Disruption of <i>ALX4</i> causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes are not well understood. Although mice carrying distinct mutations in <i>Alx4</i> have been previously reported, the perinatal lethality of homozygous mutants together with dynamic patterns of <i>Alx4</i> expression in multiple tissues have hindered systematic elucidation of the cellular and molecular mechanisms involving Alx4 in organogenesis and disease pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We report generation of <i>Alx4</i>^<i>f/f</i> conditional mice and show that tissue-specific Cre-mediated inactivation of <i>Alx4</i> in cranial neural crest and limb bud mesenchyme, respectively, recapitulated craniofacial and limb developmental defects as found in <i>Alx4</i>-null mice but without affecting postnatal survival. While <i>Alx4</i>-null mice that survive postnatally exhibited dorsal alopecia, mice lacking <i>Alx4</i> function in the neural crest lineage exhibited a highly restricted region of hair loss over the anterior skull whereas mice lacking <i>Alx4</i> in the cranial mesoderm lineage exhibited normal hair development, suggesting that Alx4 plays partly redundant roles in multiple cell lineages during hair follicle development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The <i>Alx4</i>^<i>f/f</i> mice provide a valuable resource for systematic investigation of cell type- and stage-specific function of ALX family transcription factors in development and disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 10","pages":"940-948"},"PeriodicalIF":2.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119073","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":"Analysis of changes in the action potential morphology of the mouse sinoatrial node true pacemaker cells during ontogenetic development in vitro and in silico","authors":"Alexander Ryvkin,&nbsp;Arseniy Furman,&nbsp;Elena Lebedeva,&nbsp;Mikhail Gonotkov","doi":"10.1002/dvdy.701","DOIUrl":"10.1002/dvdy.701","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maturation of the mouse is accompanied by the increase in heart rate. However, the mechanisms underlying this process remain unclear. We performed an action potentials (APs) recordings in mouse sinoatrial node (SAN) true pacemaker cells and in silico analysis to clarify the mechanisms underlying pre–postnatal period heart rate changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The APs of true pacemaker cells at different stages had similar configurations and <i>dV</i>/<i>dt</i>_max values. The cycle length, action potential duration (APD₉₀), maximal diastolic potential (MDP), and AP amplitude decreased, meanwhile the velocity of diastolic depolarization (DDR) increased from E12.5 stage to adult. Using a pharmacological approach we found that in SAN true pacemaker cells ivabradine reduces the DDR and the cycle length significantly stronger in E12.5 than in newborn and adult mice, whereas the effects of Ni²⁺ and nifedipine were significantly stronger in adult mice. Computer simulations further suggested that the density of the hyperpolarization–activated pacemaker сurrent (<i>I</i>_<i>f</i>) decreased during development, whereas transmembrane and intracellular Ca²⁺ flows increased.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The ontogenetic decrease in <i>I</i>_K1 density from E12.5 to adult leads to depolarization of MDP to the voltage range in which calcium currents are activated, thereby shifting the balance from the “membrane-clock” to the “calcium-clock.”</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 10","pages":"895-905"},"PeriodicalIF":2.0,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068264","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":"Establishment of a Diamond-Blackfan anemia like model in zebrafish","authors":"Yiming Ling,&nbsp;Jiaye Wu,&nbsp;Yushi Liu,&nbsp;Panpan Meng,&nbsp;Ying Sun,&nbsp;Dejian Zhao,&nbsp;Qing Lin","doi":"10.1002/dvdy.703","DOIUrl":"10.1002/dvdy.703","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anemia is defined as a lack of erythrocytes, low hemoglobin levels, or abnormal erythrocyte morphology. Diamond-Blackfan anemia (DBA) is a rare and severe congenital hypoplastic anemia that occurs due to the dominant inheritance of a ribosomal protein gene mutation. Even rarer is a case described as Diamond-Blackfan anemia like (DBAL), which occurs due to a loss-of-function <i>EPO</i> mutation recessive inheritance. The effective cures for DBAL are bone marrow transfusion and treatment with erythropoiesis-stimulating agents (ESAs). To effectively manage the condition, construction of DBAL models to identify new medical methods or screen drugs are necessary.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, an <i>epoa</i>-deficient mutant zebrafish called <i>epoa</i>^<i>szy8</i> was generated to model DBAL. The <i>epoa</i>-deficiency in zebrafish caused developmental defects in erythroid cells, leading to severe congenital anemia. Using the DBAL model, we validated a loss-of-function <i>EPO</i> mutation using an in vivo functional analysis and explored the ability of ESAs to alleviate congenital anemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Together, our study demonstrated that <i>epoa</i> deficiency in zebrafish leads to a phenotype resembling DBAL. The DBAL zebrafish model was found to be beneficial for the in vivo assessment of patient-derived <i>EPO</i> variants with unclear implications and for devising potential therapeutic approaches for DBAL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 10","pages":"906-921"},"PeriodicalIF":2.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049052","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}