John P Marquart, Qian Nie, Tessa Gonzalez, Angie C Jelin, Ulrich Broeckel, Amy J Wagner, Honey V Reddi
{"title":"Genetics and Genomics of Gastroschisis, Elucidating a Potential Genetic Etiology for the Most Common Abdominal Defect: A Systematic Review.","authors":"John P Marquart, Qian Nie, Tessa Gonzalez, Angie C Jelin, Ulrich Broeckel, Amy J Wagner, Honey V Reddi","doi":"10.3390/jdb12040034","DOIUrl":"https://doi.org/10.3390/jdb12040034","url":null,"abstract":"<p><p>(1) Background: The exact etiology for gastroschisis, the most common abdominal defect, is yet to be known, despite the rising prevalence of this condition. The leading theory suggests an increased familial risk, indicating a possible genetic component possibly in the context of environmental risk factors. This systematic review aims to summarize the studies focused on the identification of a potential genetic etiology for gastroschisis to elucidate the status of the field. (2) Methods: Following the PRISMA-ScR method, Pubmed and Google Scholar were searched, and eligible publications were mined for key data fields such as study aims, cohort demographics, technologies used, and outcomes in terms of genes identified. Data from 14 human studies, with varied cohort sizes from 40 to 1966 individuals for patient vs. healthy controls, respectively, were mined to delineate the technologies evaluated. (3) Results: Our results continue the theory that gastroschisis is likely caused by gene-environment interactions. The 14 studies utilized traditional methodologies that may not be adequate to identify genetic involvement in gastroschisis. (4) Conclusions: The etiology of gastroschisis continues to remain elusive. A combination of omics and epigenetic evaluation studies would help delineate a possible genetic etiology for gastroschisis.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894984","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":"Comprehensive Predictions of Mef2-Mediated Chromatin Loops, Which May Inhibit Ubx Binding by Blocking Low-Affinity Binding Sites.","authors":"Katrin Domsch","doi":"10.3390/jdb12040033","DOIUrl":"https://doi.org/10.3390/jdb12040033","url":null,"abstract":"<p><p>Gene regulation depends on the interaction between chromatin-associated factors, such as transcription factors (TFs), which promote chromatin loops to ensure tight contact between enhancer and promoter regions. So far, positive interactions that lead to gene activation have been the main focus of research, but regulations related to blocking or inhibiting factor binding are also essential to maintaining a defined cellular status. To understand these interactions in greater detail, I investigated the possibility of the muscle differentiation factor Mef2 to prevent early Hox factor binding, leading to the proper timing of regulatory processes and the activation of differentiation events. My investigations relied on a collection of publicly available genome-wide binding data sets of Mef2 and Ubx (as the Hox factor), Capture-C interactions, and ATAC-seq analysis in <i>Mef2</i> mutant cells. The analysis indicated that Mef2 can form possible chromatin loops to Ubx-bound regions. These regions contain low-affinity Ubx binding sites, and the chromatin architecture is independent of Mef2's function. High levels of Ubx may disrupt the loops and allow specific Ubx bindings to regulate defined targets. In summary, my investigations highlight that the use of many publicly available data sets enables computational approaches to make robust predictions and, for the first time, suggest a molecular function of Mef2 as a preventer of Hox binding, indicating that it may act as a timer for muscle differentiation.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894982","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}
Paige L Snider, Elizabeth A Sierra Potchanant, Catalina Matias, Donna M Edwards, Jeffrey J Brault, Simon J Conway
{"title":"The Loss of Tafazzin Transacetylase Activity Is Sufficient to Drive Testicular Infertility.","authors":"Paige L Snider, Elizabeth A Sierra Potchanant, Catalina Matias, Donna M Edwards, Jeffrey J Brault, Simon J Conway","doi":"10.3390/jdb12040032","DOIUrl":"https://doi.org/10.3390/jdb12040032","url":null,"abstract":"<p><p>Barth syndrome (BTHS) is a rare, infantile-onset, X-linked mitochondriopathy exhibiting a variable presentation of failure to thrive, growth insufficiency, skeletal myopathy, neutropenia, and heart anomalies due to mitochondrial dysfunction secondary to inherited TAFAZZIN transacetylase mutations. Although not reported in BTHS patients, male infertility is observed in several <i>Tafazzin</i> (<i>Taz</i>) mouse alleles and in a <i>Drosophila</i> mutant. Herein, we examined the male infertility phenotype in a BTHS-patient-derived <i>D75H</i> point-mutant knockin mouse (<i>Taz<sup>PM</sup></i>) allele that expresses a mutant protein lacking transacetylase activity. Neonatal and adult <i>Taz<sup>PM</sup></i> testes were hypoplastic, and their epididymis lacked sperm. Histology and biomarker analysis revealed <i>Taz<sup>PM</sup></i> spermatogenesis is arrested prior to sexual maturation due to an inability to undergo meiosis and the generation of haploid spermatids. Moreover, <i>Taz<sup>PM</sup></i> testicular mitochondria were found to be structurally abnormal, and there was an elevation of p53-dependent apoptosis within <i>Taz<sup>PM</sup></i> seminiferous tubules. Immunoblot analysis revealed that <i>Taz<sup>PM</sup></i> gamete genome integrity was compromised, and both histone γ-H2Ax and Nucleoside diphosphate kinase-5 protein expression were absent in juvenile <i>Taz<sup>PM</sup></i> testes when compared to controls. We demonstrate that Taz-mediated transacetylase activity is required within mitochondria for normal spermatogenesis, and its absence results in meiotic arrest. We hypothesize that elevated <i>Taz<sup>PM</sup></i> spermatogonial apoptosis causes azoospermia and complete infertility.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894985","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}
Fumiko Yamamoto, Takeshi Yokoyama, Yan Su, Masataka G Suzuki
{"title":"Transcriptomic Evidence for Cell-Autonomous Sex Differentiation of the Gynandromorphic Fat Body in the Silkworm, <i>Bombyx mori</i>.","authors":"Fumiko Yamamoto, Takeshi Yokoyama, Yan Su, Masataka G Suzuki","doi":"10.3390/jdb12040031","DOIUrl":"10.3390/jdb12040031","url":null,"abstract":"<p><p>The classic model of sex determination in insects suggests that they do not have sex hormones and that sex is determined in a cell-autonomous manner. On the other hand, there is accumulating evidence that the development of secondary sexual traits is controlled in a non-cell-autonomous manner through external factors. To evaluate the degrees of the cell-autonomous and non-cell-autonomous regulation of secondary sexual trait development, we analyzed the dynamics of the sexually dimorphic transcriptome in gynandromorphic individuals of the <i>mo</i> mutant strain in the silkworm <i>Bombyx mori</i>. The silkworm possesses a female heterogametic sex-determination system (ZZ = male/ZW = female), where the master regulatory gene for femaleness, <i>Feminizer</i> (<i>Fem</i>), is located in the W chromosome. As a secondary sexual trait, we focused on the fat body, which shows remarkable differences between the sexes during the last instar larval stage. A comparison of the transcriptomes between the fat bodies of male and female larvae identified 232 sex-differentially expressed genes (S-DEGs). The proportions of ZZ and ZW cells constituting the fat body of the gynandromorphic larvae were calculated according to the expression level of the <i>Fem</i>. Based on the obtained values, the expression level of each S-DEG was estimated, assuming that the levels of S-DEG expression were determined according to the proportion of ZZ and ZW cells. The estimated expression levels of 207 out of 232 S-DEGs were strongly correlated with the corresponding S-DEG expression level of the gynandromorphic fat body, determined by RNA-seq. These results strongly suggest that most of the sexually dimorphic transcriptome in the fat body is regulated in a cell-autonomous manner.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710266","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}
Daniel Halloran, Venu Pandit, Kelechi Chukwuocha, Anja Nohe
{"title":"Methyl-Beta-Cyclodextrin Restores Aberrant Bone Morphogenetic Protein 2-Signaling in Bone Marrow Stromal Cells Obtained from Aged C57BL/6 Mice.","authors":"Daniel Halloran, Venu Pandit, Kelechi Chukwuocha, Anja Nohe","doi":"10.3390/jdb12040030","DOIUrl":"10.3390/jdb12040030","url":null,"abstract":"<p><p>During aging, disruptions in various signaling pathways become more common. Some older patients will exhibit irregular bone morphogenetic protein (BMP) signaling, which can lead to osteoporosis (OP)-a debilitating bone disease resulting from an imbalance between osteoblasts and osteoclasts. In 2002, the Food and Drug Administration (FDA) approved recombinant human BMP-2 (rhBMP-2) for use in spinal fusion surgeries as it is required for bone formation. However, complications with rhBMP-2 arose and primary osteoblasts from OP patients often fail to respond to BMP-2. Although patient samples are available for study, previous medical histories can impact results. Consequently, the C57BL/6 mouse line serves as a valuable model for studying OP and aging. We find that BMP receptor type Ia (BMPRIa) is upregulated in the bone marrow stromal cells (BMSCs) of 15-month-old mice, consistent with prior data. Furthermore, conjugating BMP-2 with Quantum Dots (QDot<sup>®</sup>s) allows effective binding to BMPRIa, creating a fluorescent tag for BMP-2. Furthermore, after treating BMSCs with methyl-β-cyclodextrin (MβCD), a disruptor of cellular endocytosis, BMP signaling is restored in 15-month-old mice, as shown by von Kossa assays. MβCD has the potential to restore BMPRIa function, and the BMP signaling pathway offers a promising avenue for future OP therapies.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710257","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}
Kai Kitamura, Kyoko Saito, Takeshi Homma, Aimi Fuyuki, Sawa Onouchi, Shouichiro Saito
{"title":"Prosaposin/Saposin Expression in the Developing Rat Olfactory and Vomeronasal Epithelia.","authors":"Kai Kitamura, Kyoko Saito, Takeshi Homma, Aimi Fuyuki, Sawa Onouchi, Shouichiro Saito","doi":"10.3390/jdb12040029","DOIUrl":"10.3390/jdb12040029","url":null,"abstract":"<p><p>Prosaposin is a glycoprotein widely conserved in vertebrates, and it acts as a precursor for saposins that accelerate hydrolysis in lysosomes or acts as a neurotrophic factor without being processed into saposins. Neurogenesis in the olfactory neuroepithelia, including the olfactory epithelium (OE) and the vomeronasal epithelium (VNE), is known to occur throughout an animal's life, and mature olfactory neurons (ORNs) and vomeronasal receptor neurons (VRNs) have recently been revealed to express prosaposin in the adult olfactory organ. In this study, the expression of prosaposin in the rat olfactory organ during postnatal development was examined. In the OE, prosaposin immunoreactivity was observed in mature ORNs labeled using olfactory marker protein (OMP) from postnatal day (P) 0. Immature ORNs showed no prosaposin immunoreactivity throughout the examined period. In the VNE, OMP-positive VRNs were mainly observed in the basal region of the VNE on P10 and showed an adult-like distribution from P20. On the other hand, prosaposin immunoreactivity was observed in VRNs from P0, suggesting that not only mature VRNs but also immature VRNs express prosaposin. This study raises the possibility that prosaposin is required for the normal development of the olfactory organ and has different roles in the OE and the VNE.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710260","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":"How the Oocyte Nucleolus Is Turned into a Karyosphere: The Role of Heterochromatin and Structural Proteins.","authors":"Venera Nikolova, Maya Markova, Ralitsa Zhivkova, Irina Chakarova, Valentina Hadzhinesheva, Stefka Delimitreva","doi":"10.3390/jdb12040028","DOIUrl":"https://doi.org/10.3390/jdb12040028","url":null,"abstract":"<p><p>Oocyte meiotic maturation includes large-scale chromatin remodeling as well as cytoskeleton and nuclear envelope rearrangements. This review addresses the dynamics of key cytoskeletal proteins (tubulin, actin, vimentin, and cytokeratins) and nuclear envelope proteins (lamin A/C, lamin B, and the nucleoporin Nup160) in parallel with chromatin reorganization in maturing mouse oocytes. A major feature of this reorganization is the concentration of heterochromatin into a spherical perinucleolar rim called surrounded nucleolus or karyosphere. In early germinal vesicle (GV) oocytes with non-surrounded nucleolus (without karyosphere), lamins and Nup160 are at the nuclear envelope while cytoplasmic cytoskeletal proteins are outside the nucleus. At the beginning of karyosphere formation, lamins and Nup160 follow the heterochromatin relocation assembling a new spherical structure in the GV. In late GV oocytes with surrounded nucleolus (fully formed karyosphere), the nuclear envelope gradually loses its integrity and cytoplasmic cytoskeletal proteins enter the nucleus. At germinal vesicle breakdown, lamin B occupies the karyosphere interior while all the other proteins stay at the karyosphere border or connect to chromatin. In metaphase oocytes, lamin A/C surrounds the spindle, Nup160 localizes to its poles, actin and lamin B are attached to the spindle fibers, and cytoplasmic intermediate filaments associate with both the spindle fibers and the metaphase chromosomes.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501608","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}
Samuel Liu, Kellianne D Alexander, Michael M Francis
{"title":"Neural Circuit Remodeling: Mechanistic Insights from Invertebrates.","authors":"Samuel Liu, Kellianne D Alexander, Michael M Francis","doi":"10.3390/jdb12040027","DOIUrl":"https://doi.org/10.3390/jdb12040027","url":null,"abstract":"<p><p>As nervous systems mature, neural circuit connections are reorganized to optimize the performance of specific functions in adults. This reorganization of connections is achieved through a remarkably conserved phase of developmental circuit remodeling that engages neuron-intrinsic and neuron-extrinsic molecular mechanisms to establish mature circuitry. Abnormalities in circuit remodeling and maturation are broadly linked with a variety of neurodevelopmental disorders, including autism spectrum disorders and schizophrenia. Here, we aim to provide an overview of recent advances in our understanding of the molecular processes that govern neural circuit remodeling and maturation. In particular, we focus on intriguing mechanistic insights gained from invertebrate systems, such as the nematode <i>Caenorhabditis elegans</i> and the fruit fly <i>Drosophila melanogaster</i>. We discuss how transcriptional control mechanisms, synaptic activity, and glial engulfment shape specific aspects of circuit remodeling in worms and flies. Finally, we highlight mechanistic parallels across invertebrate and mammalian systems, and prospects for further advances in each.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501609","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}
Ling Sun, Yan Wang, Mo Yang, Zhuang-Ju Xu, Juan Miao, Ying Bai, Tao Lin
{"title":"Delayed Blastocyst Formation Reduces the Quality and Hatching Ability of Porcine Parthenogenetic Blastocysts by Increasing DNA Damage, Decreasing Cell Proliferation, and Altering Transcription Factor Expression Patterns.","authors":"Ling Sun, Yan Wang, Mo Yang, Zhuang-Ju Xu, Juan Miao, Ying Bai, Tao Lin","doi":"10.3390/jdb12040026","DOIUrl":"https://doi.org/10.3390/jdb12040026","url":null,"abstract":"<p><p>The purpose of this study was to investigate the influence of blastocyst formation timing on the quality of porcine embryos derived from parthenogenetic activation. Newly formed blastocysts at days 6, 7, and 8 of culture [termed formation 6, 7, and 8 blastocysts (F6, F7, and F8 blastocysts)] were obtained, and a series of parameters related to the quality of blastocysts, including apoptosis incidents, DNA replication, pluripotent factors, and blastocyst hatching capacity, were assessed. Delayed blastocyst formation (F7 and/or F8 blastocysts) led to increased levels of ROS, DNA damage, and apoptosis while decreasing the mitochondrial membrane potential, DNA replication, Oct4 levels, and numbers of Sox2-positive cells. F7 blastocysts showed a significantly reduced hatching rate compared to F6 blastocysts; however, F8 blastocysts were unable to develop to the hatching stage. Collectively, our findings suggest a negative correlation between delayed blastocyst formation and blastocyst quality.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501607","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":"Myotube Guidance: Shaping up the Musculoskeletal System.","authors":"Aaron N Johnson","doi":"10.3390/jdb12030025","DOIUrl":"10.3390/jdb12030025","url":null,"abstract":"<p><p>Myofibers are highly specialized contractile cells of skeletal muscles, and dysregulation of myofiber morphogenesis is emerging as a contributing cause of myopathies and structural birth defects. Myotubes are the myofiber precursors and undergo a dramatic morphological transition into long bipolar myofibers that are attached to tendons on two ends. Similar to axon growth cones, myotube leading edges navigate toward target cells and form cell-cell connections. The process of myotube guidance connects myotubes with the correct tendons, orients myofiber morphology with the overall body plan, and generates a functional musculoskeletal system. Navigational signaling, addition of mass and volume, and identification of target cells are common events in myotube guidance and axon guidance, but surprisingly, the mechanisms regulating these events are not completely overlapping in myotubes and axons. This review summarizes the strategies that have evolved to direct myotube leading edges to predetermined tendon cells and highlights key differences between myotube guidance and axon guidance. The association of myotube guidance pathways with developmental disorders is also discussed.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"12 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288787","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}