Journal of Developmental Biology最新文献

{"title":"Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts","authors":"Daniel R Halloran, Brian P. Heubel, Connor MacMurray, D. Root, M. Eskander, Sean McTague, Heather Pelkey, A. Nohe","doi":"10.3390/jdb10010006","DOIUrl":"https://doi.org/10.3390/jdb10010006","url":null,"abstract":"Proper formation of the skeleton during development is crucial for the mobility of humans and the maintenance of essential organs. The production of bone is regulated by osteoblasts and osteoclasts. An imbalance of these cells can lead to a decrease in bone mineral density, which leads to fractures. While many studies are emerging to understand the role of osteoblasts, less studies are present about the role of osteoclasts. This present study utilized bone marrow cells isolated directly from the bone marrow of femoral heads obtained from osteoarthritic (OA) patients after undergoing hip replacement surgery. Here, we used tartrate resistant acid phosphatase (TRAP) staining, Cathepsin K, and nuclei to identity osteoclasts and their functionality after stimulation with macrophage-colony stimulation factor (M-CSF) and receptor activator of nuclear factor kappa-β ligand (RANKL). Our data demonstrated that isolated cells can be differentiated into functional osteoclasts, as indicated by the 92% and 83% of cells that stained positive for TRAP and Cathepsin K, respectively. Furthermore, isolated cells remain viable and terminally differentiate into osteoclasts when stimulated with RANKL. These data demonstrate that cells isolated from human femoral heads can be differentiated into osteoclasts to study bone disorders during development and adulthood.","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49384927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Immunoglobulin Superfamily Members <i>syg-2</i> and <i>syg-1</i> Regulate Neurite Development in <i>C. elegans</i>.","authors":"Dana K Tucker,&nbsp;Chloe S Adams,&nbsp;Gauri Prasad,&nbsp;Brian D Ackley","doi":"10.3390/jdb10010003","DOIUrl":"https://doi.org/10.3390/jdb10010003","url":null,"abstract":"<p><p>Neurons form elaborate networks by guiding axons and dendrites to appropriate destinations. Neurites require information about the relative body axes during the initial projection from the cell body, and failure to receive or interpret those cues correctly can result in outgrowth errors. We identified a mutation in the Ig superfamily member <i>syg-2</i> in a screen for animals with anterior/posterior (A/P) axon guidance defects. We found that <i>syg-2</i> and its cognate Ig family member <i>syg-1</i> appear to function in a linear genetic pathway to control the outgrowth of GABAergic axons. We determined that this pathway works in parallel to Wnt signaling. Specifically, mutations in <i>syg-2</i> or <i>syg-1</i> selectively affected the embryonically derived Dorsal D-type (DD) GABAergic neurons. We found no evidence that these mutations affected the Ventral D-type neurons (VD) that form later, during the first larval stage. In addition, mutations in <i>syg-1</i> or <i>syg-2</i> could result in the DD neurons forming multiple processes, becoming bipolar, rather than the expected pseudounipolar morphology. Given SYG-2's essential function in synaptogenesis of the hermaphrodite-specific neurons (HSNs), we also examined DD neuron synapses in <i>syg-2</i> mutants. We found <i>syg-2</i> mutants had a decreased number of synapses formed, but synaptic morphology was largely normal. These results provide further evidence that the GABAergic motorneurons use multiple guidance pathways during development.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"10 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9575193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of HoxB3 and Growth Factors Expression in Placentas of Various Gestational Ages.","authors":"Ilze Kreicberga,&nbsp;Anna Junga,&nbsp;Māra Pilmane","doi":"10.3390/jdb10010002","DOIUrl":"https://doi.org/10.3390/jdb10010002","url":null,"abstract":"<p><p>An evaluation of transforming growth factor beta (TGFβ), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF-2), fibroblast growth factors receptor 1 (FGFR1) and Hox-positive cells in the human placenta, and their correlation with gestational time at delivery and pregnancy outcomes, may provide not only a better understanding of the role of Hox genes and growth factors in human development, but also may be of clinical importance in reproductive medicine. This study analyzed the immunohistochemical identification of TGFβ, HGF, FGF-2, FGFR1 and HoxB3 in placentas of various gestational ages. We found few (+) TGFβ, moderate (++) FGF-2 and numerous (+++) HGF and FGFR1 positive structures. Occasional (0/+) to numerous (+++) HoxB3-positive structures were detected in different types of placental cells specifically, cytotrophoblasts, syncytiotrophoblast, extravillous trophoblasts, and Höfbauer cells. Correlating the appearance of HoxB3 staining in placentas with neonatal parameters, we found a statistically significant negative correlation with ponderal index (r = -0.323, <i>p</i> = 0.018) and positive correlation with neonate body length (r = 0.541, <i>p</i> = 0.046). The number of HoxB3-positive cells did not correlate with growth factors and gestational age, but with neonatal anthropometrical parameters, indicating the role of HoxB3 not only in placental development, but also in the longitudinal growth of the fetus. TGFβ and FGF-2 did not play a significant role in the development of the placenta beyond 22nd week of pregnancy, while HGF and FGFR1 immunoreactive cells increased with advancing gestation, indicating increasingly evolving maturation (growth, proliferation) of the placenta, especially in the third trimester.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"10 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2021-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39719458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Planar Cell Polarity Effector Fuzzy Causes Renal Hypoplasia by Disrupting Several Signaling Pathways.","authors":"Irene-Yanran Wang,&nbsp;Chen-Fang Chung,&nbsp;Sima Babayeva,&nbsp;Tamara Sogomonian,&nbsp;Elena Torban","doi":"10.3390/jdb10010001","DOIUrl":"https://doi.org/10.3390/jdb10010001","url":null,"abstract":"<p><p>In vertebrates, the planar cell polarity (PCP) pathway regulates tissue morphogenesis during organogenesis, including the kidney. Mutations in human PCP effector proteins have been associated with severe syndromic ciliopathies. Importantly, renal hypoplasia has been reported in some patients. However, the developmental disturbance that causes renal hypoplasia is unknown. Here, we describe the early onset of profound renal hypoplasia in mice homozygous for null mutation of the PCP effector gene, <i>Fuzzy</i>. We found that this phenotype is caused by defective branching morphogenesis of the ureteric bud (UB) in the absence of defects in nephron progenitor specification or in early steps of nephrogenesis. By using various experimental approaches, we show that the loss of Fuzzy affects multiple signaling pathways. Specifically, we found mild involvement of GDNF/c-Ret pathway that drives UB branching. We noted the deficient expression of molecules belonging to the Bmp, Fgf and Shh pathways. Analysis of the primary cilia in the UB structures revealed a significant decrease in ciliary length. We conclude that renal hypoplasia in the mouse <i>Fuzzy</i> mutants is caused by defective UB branching associated with dysregulation of ciliary and non-ciliary signaling pathways. Our work suggests a PCP effector-dependent pathogenetic mechanism that contributes to renal hypoplasia in mice and humans.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"10 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2021-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39963343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Development of SARS-CoV-2 Variants: The Gene Makes the Disease.","authors":"Raquel Perez-Gomez","doi":"10.3390/jdb9040058","DOIUrl":"10.3390/jdb9040058","url":null,"abstract":"<p><p>A novel coronavirus (SARS-CoV-2) emerged towards the end of 2019 that caused a severe respiratory disease in humans called COVID-19. It led to a pandemic with a high rate of morbidity and mortality that is ongoing and threatening humankind. Most of the mutations occurring in SARS-CoV-2 are synonymous or deleterious, but a few of them produce improved viral functions. The first known mutation associated with higher transmissibility, D614G, was detected in early 2020. Since then, the virus has evolved; new mutations have occurred, and many variants have been described. Depending on the genes affected and the location of the mutations, they could provide altered infectivity, transmissibility, or immune escape. To date, mutations that cause variations in the SARS-CoV-2 spike protein have been among the most studied because of the protein's role in the initial virus-cell contact and because it is the most variable region in the virus genome. Some concerning mutations associated with an impact on viral fitness have been described in the Spike protein, such as D614G, N501Y, E484K, K417N/T, L452R, and P681R, among others. To understand the impact of the infectivity and antigenicity of the virus, the mutation landscape of SARS-CoV-2 has been under constant global scrutiny. The virus variants are defined according to their origin, their genetic profile (some characteristic mutations prevalent in the lineage), and the severity of the disease they produce, which determines the level of concern. If they increase fitness, new variants can outcompete others in the population. The Alpha variant was more transmissible than previous versions and quickly spread globally. The Beta and Gamma variants accumulated mutations that partially escape the immune defenses and affect the effectiveness of vaccines. Nowadays, the Delta variant, identified around March 2021, has spread and displaced the other variants, becoming the most concerning of all lineages that have emerged. The Delta variant has a particular genetic profile, bearing unique mutations, such as T478K in the spike protein and M203R in the nucleocapsid. This review summarizes the current knowledge of the different mutations that have appeared in SARS-CoV-2, mainly on the spike protein. It analyzes their impact on the protein function and, subsequently, on the level of concern of different variants and their importance in the ongoing pandemic.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"9 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39750133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Evolutionary Perspective on Hox Binding Site Preferences in Two Different Tissues.","authors":"Laura Folkendt,&nbsp;Ingrid Lohmann,&nbsp;Katrin Domsch","doi":"10.3390/jdb9040057","DOIUrl":"https://doi.org/10.3390/jdb9040057","url":null,"abstract":"<p><p>Transcription factor (TF) networks define the precise development of multicellular organisms. While many studies focused on TFs expressed in specific cell types to elucidate their contribution to cell specification and differentiation, it is less understood how broadly expressed TFs perform their precise functions in the different cellular contexts. To uncover differences that could explain tissue-specific functions of such TFs, we analyzed here genomic chromatin interactions of the broadly expressed <i>Drosophila</i> Hox TF Ultrabithorax (Ubx) in the mesodermal and neuronal tissues using bioinformatics. Our investigations showed that Ubx preferentially interacts with multiple yet tissue-specific chromatin sites in putative regulatory regions of genes in both tissues. Importantly, we found the classical Hox/Ubx DNA binding motif to be enriched only among the neuronal Ubx chromatin interactions, whereas a novel Ubx-like motif with rather low predicted Hox affinities was identified among the regions bound by Ubx in the mesoderm. Finally, our analysis revealed that tissues-specific Ubx chromatin sites are also different with regards to the distribution of active and repressive histone marks. Based on our data, we propose that the tissue-related differences in Ubx binding behavior could be a result of the emergence of the mesoderm as a new germ layer in triploblastic animals, which might have required the Hox TFs to relax their binding specificity.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"9 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2021-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39750131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HOX Protein Activity Regulation by Cellular Localization.","authors":"Laure Bridoux,&nbsp;Françoise Gofflot,&nbsp;René Rezsohazy","doi":"10.3390/jdb9040056","DOIUrl":"https://doi.org/10.3390/jdb9040056","url":null,"abstract":"<p><p>While the functions of <i>HOX</i> genes have been and remain extensively studied in distinct model organisms from flies to mice, the molecular biology of HOX proteins remains poorly documented. In particular, the mechanisms involved in regulating the activity of HOX proteins have been poorly investigated. Nonetheless, based on data available from other well-characterized transcription factors, it can be assumed that HOX protein activity must be finely tuned in a cell-type-specific manner and in response to defined environmental cues. Indeed, records in protein-protein interaction databases or entries in post-translational modification registries clearly support that HOX proteins are the targets of multiple layers of regulation at the protein level. In this context, we review here what has been reported and what can be inferred about how the activities of HOX proteins are regulated by their intracellular distribution.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"9 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2021-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39750130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Characterization of HOXA2 and HOXA3 Binding Properties.","authors":"Joshua Mallen,&nbsp;Manisha Kalsan,&nbsp;Peyman Zarrineh,&nbsp;Laure Bridoux,&nbsp;Shandar Ahmad,&nbsp;Nicoletta Bobola","doi":"10.3390/jdb9040055","DOIUrl":"https://doi.org/10.3390/jdb9040055","url":null,"abstract":"<p><p>The highly conserved HOX homeodomain (HD) transcription factors (TFs) establish the identity of different body parts along the antero-posterior axis of bilaterian animals. Segment diversification and the morphogenesis of different structures is achieved by generating precise patterns of HOX expression along the antero-posterior axis and by the ability of different HOX TFs to instruct unique and specific transcriptional programs. However, HOX binding properties in vitro, characterised by the recognition of similar AT-rich binding sequences, do not account for the ability of different HOX to instruct segment-specific transcriptional programs. To address this problem, we previously compared HOXA2 and HOXA3 binding in vivo. Here, we explore if sequence motif enrichments observed in vivo are explained by binding affinities in vitro. Unexpectedly, we found that the highest enriched motif in HOXA2 peaks was not recognised by HOXA2 in vitro, highlighting the importance of investigating HOX binding in its physiological context. We also report the ability of HOXA2 and HOXA3 to heterodimerise, which may have functional consequences for the HOX patterning function in vivo.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"9 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2021-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39750128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental Aspects of SARS-CoV-2, Potential Role of Exosomes and Their Impact on the Human Transcriptome.","authors":"Navneet Dogra, Carmen Ledesma-Feliciano, Rwik Sen","doi":"10.3390/jdb9040054","DOIUrl":"10.3390/jdb9040054","url":null,"abstract":"<p><p>With over 4.8 million deaths within 2 years, time is of the essence in combating COVID-19. The infection now shows devastating impacts on the younger population, who were not previously predicted to be vulnerable, such as in the older population. COVID-19-related complications have been reported in neonates whose mothers were infected with SARS-CoV-2 during pregnancy, and in children who get infected. Hence, a deeper understanding of the pathophysiology of COVID-19 during various developmental stages and placental transmission is essential. Although a connection has not yet been established between exosomal trafficking and the placental transmission of COVID-19, reports indicate that SARS-CoV-2 components may be trafficked between cells through exosomes. As the infection spreads, the transcriptome of cells is drastically perturbed, e.g., through the severe upregulation of several immune-related genes. Consequently, a major outcome of COVID-19 is an elevated immune response and the detection of viral RNA transcripts in host tissue. In this direction, this review focuses on SARS-CoV-2 virology, its in utero transmission from infected pregnant mothers to fetuses, SARS-CoV-2 and exosomal cellular trafficking, transcriptomic impacts, and RNA-mediated therapeutics against COVID-19. Future research will establish stronger connections between the above processes to develop diagnostic and therapeutic solutions towards COVID-19 and similar viral outbreaks.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"9 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39750129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"At What Cost? Trade-Offs and Influences on Energetic Investment in Tail Regeneration in Lizards Following Autotomy.","authors":"James I Barr, Catherine A Boisvert, Philip W Bateman","doi":"10.3390/jdb9040053","DOIUrl":"10.3390/jdb9040053","url":null,"abstract":"<p><p>Caudal autotomy, the ability to shed a portion of the tail, is a widespread defence strategy among lizards. Following caudal autotomy, and during regeneration, lizards face both short- and long-term costs associated with the physical loss of the tail and the energy required for regeneration. As such, the speed at which the individual regenerates its tail (regeneration rate) should reflect the fitness priorities of the individual. However, multiple factors influence the regeneration rate in lizards, making inter-specific comparisons difficult and hindering broader scale investigations. We review regeneration rates for lizards and tuatara from the published literature, discuss how species' fitness priorities and regeneration rates are influenced by specific, life history and environmental factors, and provide recommendations for future research. Regeneration rates varied extensively (0-4.3 mm/day) across the 56 species from 14 family groups. Species-specific factors, influencing regeneration rates, varied based on the type of fracture plane, age, sex, reproductive season, and longevity. Environmental factors including temperature, photoperiod, nutrition, and stress also affected regeneration rates, as did the method of autotomy induction, and the position of the tail also influenced regeneration rates for lizards. Additionally, regeneration could alter an individual's behaviour, growth, and reproductive output, but this varied depending on the species.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"9 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39750127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}