IF 1.5 4区生物学

genesis Pub Date : 2023-01-19 DOI: 10.1002/dvg.23507

Kelly Bush, Vanessa Cervantes, Jennifer Q. Yee, Rachel H. Klein, Paul S. Knoepfler

{"title":"A knockout-first model of H3f3a gene targeting leads to developmental lethality","authors":"Kelly Bush, Vanessa Cervantes, Jennifer Q. Yee, Rachel H. Klein, Paul S. Knoepfler","doi":"10.1002/dvg.23507","DOIUrl":"10.1002/dvg.23507","url":null,"abstract":"<div>\u0000 \u0000 Histone variant H3.3 is encoded by two genes, H3f3a and H3f3b, which can be expressed differentially depending on tissue type. Previous work in our lab has shown that knockout of H3f3b causes some neonatal lethality and infertility in mice, and chromosomal defects in mouse embryonic fibroblasts (MEFs). Studies of H3f3a and H3f3b null mice by others have produced generally similar phenotypes to what we found in our H3f3b nulls, but the relative impacts of the loss of either H3f3a or H3f3b have varied depending on the approach and genetic background. Here we used a knockout-first approach to target the H3f3a gene for inactivation in C57BL6 mice. Homozygous H3f3a targeting produced a lethal phenotype at or before birth. E13.5 null embryos had some potential morphological differences from WT littermates including smaller size and reduced head size. An E18.5 null embryo was smaller than its control littermates with several potential defects including small head and brain size as well as small lungs, which would be consistent with a late gestation lethal phenotype. Despite a reduction in H3.3 and total H3 protein levels, the only histone H3 post-translational modification in the small panel assessed that was significantly altered was the unique H3.3 mark phospho-Serine31, which was consistently increased in null neurospheres. H3f3a null neurospheres also exhibited consistent gene expression changes including in protocadherins. Overall, our findings are consistent with the model that there are differential, cell-type-specific contributions of H3f3a and H3f3b to H3.3 functions in epigenetic and developmental processes.\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10038898/pdf/nihms-1869288.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9656485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Augmentation of bone morphogenetic protein signaling in cranial neural crest cells in mice deforms skull base due to premature fusion of intersphenoidal synchondrosis 小鼠颅神经嵴细胞中骨形态发生蛋白信号的增强导致蝶间软骨联合症早期融合导致颅底畸形

IF 1.5 4区生物学

genesis Pub Date : 2023-01-09 DOI: 10.1002/dvg.23509

Hiroki Ueharu, Haichun Pan, Satoru Hayano, Karen Zapien-Guerra, Jingwen Yang, Yuji Mishina

{"title":"Augmentation of bone morphogenetic protein signaling in cranial neural crest cells in mice deforms skull base due to premature fusion of intersphenoidal synchondrosis","authors":"Hiroki Ueharu, Haichun Pan, Satoru Hayano, Karen Zapien-Guerra, Jingwen Yang, Yuji Mishina","doi":"10.1002/dvg.23509","DOIUrl":"10.1002/dvg.23509","url":null,"abstract":"<div>\u0000 \u0000 Craniofacial anomalies (CFAs) are a diverse group of disorders affecting the shapes of the face and the head. Malformation of the cranial base in humans leads CFAs, such as midfacial hypoplasia and craniosynostosis. These patients have significant burdens associated with breathing, speaking, and chewing. Invasive surgical intervention is the current primary option to correct these structural deficiencies. Understanding molecular cellular mechanism for craniofacial development would provide novel therapeutic options for CFAs. In this study, we found that enhanced bone morphogenetic protein (BMP) signaling in cranial neural crest cells (NCCs) (P0-Cre;caBmpr1a mice) causes premature fusion of intersphenoid synchondrosis (ISS) resulting in leading to short snouts and hypertelorism. Histological analyses revealed reduction of proliferation and higher cell death in ISS at postnatal day 3. We demonstrated to prevent the premature fusion of ISS in P0-Cre;caBmpr1a mice by injecting a p53 inhibitor Pifithrin-α to the pregnant mother from E15.5 to E18.5, resulting in rescue from short snouts and hypertelorism. We further demonstrated to prevent premature fusion of cranial sutures in P0-Cre;caBmpr1a mice by injecting Pifithrin-α through E8.5 to E18.5. These results suggested that enhanced BMP-p53-induced cell death in cranial NCCs causes premature fusion of ISS and sutures in time-dependent manner.\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9291648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Tailup expression in Drosophila larval and adult cardiac valve cells 果蝇幼虫和成虫心脏瓣膜细胞中Tailup的表达

IF 1.5 4区生物学

genesis Pub Date : 2022-12-22 DOI: 10.1002/dvg.23506

Christian Meyer, Laetitia Bataillé, Maik Drechsler, Achim Paululat

{"title":"Tailup expression in Drosophila larval and adult cardiac valve cells","authors":"Christian Meyer, Laetitia Bataillé, Maik Drechsler, Achim Paululat","doi":"10.1002/dvg.23506","DOIUrl":"10.1002/dvg.23506","url":null,"abstract":"In Drosophila larvae, the direction of blood flow within the heart tube, as well as the diastolic filling of the posterior heart chamber, is regulated by a single cardiac valve. This valve is sufficient to close the heart tube at the junction of the ventricle and the aorta and is formed by only two cells; both are integral parts of the heart tube. The valve cells regulate hemolymph flow by oscillating between a spherical and a flattened cell shape during heartbeats. At the spherical stage, the opposing valve cells close the heart lumen. The dynamic cell shape changes of valve cells are supported by a dense, criss-cross orientation of myofibrils and the presence of the valvosomal compartment, a large intracellular cavity. Both structures are essential for the valve cells' function. In a screen for factors specifically expressed in cardiac valve cells, we identified the transcription factor Tailup. Knockdown of tailup causes abnormal orientation and differentiation of cardiac muscle fibers in the larval aorta and inhibits the formation of the ventral longitudinal muscle layer located underneath the heart tube in the adult fly and affects myofibrillar orientation of valve cells. Furthermore, we have identified regulatory sequences of tup that control the expression of tailup in the larval and adult valve cells.","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.23506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9184101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Precise modulation of embryonic development through optogenetics 通过光遗传学精确调节胚胎发育

IF 1.5 4区生物学

genesis Pub Date : 2022-12-07 DOI: 10.1002/dvg.23505

Huaxun Fan, Collin Barnes, Hyojeong Hwang, Kai Zhang, Jing Yang

引用次数: 2

Sous la dictée : les usages du microphone 听写下：麦克风的使用

IF 1.5 4区生物学

genesis Pub Date : 2022-12-01 DOI: 10.4000/genesis.7694

Jean-François Duclos

引用次数: 0

L’antiquité des machines à écrire 打字机的古代