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Unraveling the Mechanisms That Regulate Osteoclast Differentiation: A Review of Current Advances
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2025-02-17 DOI: 10.1002/dvg.70012
Sai Zhang, Meng Gao, Shuzhe Song, Tongdan Zhao, Bianhua Zhou, Hongwei Wang, Weishun Tian, Wenpeng Zhao, Jing Zhao

Osteoporosis is a metabolic bone disease primarily caused by a decreased bone formation and increased bone resorption. Osteoclasts are a special class of terminally differentiated cells that play an important role in normal bone remodeling and bone loss in osteoporosis as well as in a variety of osteolytic diseases. Osteoclasts can be differentiated from monocyte–macrophage cells of the hematopoietic system; they are the key cells in bone resorption. Osteoclast formation and differentiation are regulated by various cytokines and transcription factors. In this review, we summarize recent advances in research on the regulation of osteoclast differentiation and function by factors such as M-CSF, RANKL, AP-1, NFATC1, MITF, and PU.1. Understanding these cytokines and transcription factors can not only help identify targets for osteoclast differentiation but also aid in intervening in the treatment of osteoclast-related diseases.

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引用次数: 0
A New Targeted Transgenic Mouse Line for the Study of Protocadherin γC4
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2025-02-09 DOI: 10.1002/dvg.70010
Cathy M. McLeod, Camille M. Hanes, Leah C. Fuller, Samjhana Bhandari, Hannah G. Lanthier, Robert W. Burgess, Joshua A. Weiner, Andrew M. Garrett

The γ-protocadherins (γ-Pcdhs) comprise 22 homophilic cell adhesion molecule isoforms, expressed from the Pcdhg gene cluster via promoter choice mechanisms that serve many crucial functions during neural development. Emerging evidence supports the hypothesis that distinct isoforms have unique functions. The γC4 isoform, which is expressed from the Pcdhgc4 promoter and includes its unique variable exon, is the sole γ-Pcdh isoform essential for the postnatal survival in mice. Here we describe a new mouse line (C4-GFP) in which Pcdhgc4 with a C-terminal GFP tag is expressed from the Rosa26 locus following excision of a lox-Stop-lox cassette by Cre recombinase. We report that restricted expression of this transgene in the nervous system using Nestin-Cre is sufficient to rescue the neonatal lethality of mice mutant for Pcdhgc4. This new line will be a vital tool for dissecting mechanisms underlying the functions of this essential cell adhesion molecule gene, mutations in which have been associated with neurodevelopmental disorders in humans.

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引用次数: 0
Meet Our Editorial Board—Genesis. An Interview With, Susan Mackem, National Cancer Institute, Maryland, USA
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2025-01-29 DOI: 10.1002/dvg.70011
Paul Trevorrow, Susan Mackem
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引用次数: 0
Meet Our Editorial Board—Genesis. An Interview With Yevgenya Grinblat, University of Wisconsin-Madison, Wisconsin, USA
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2025-01-27 DOI: 10.1002/dvg.70005
Paul Trevorrow, Yevgenya Grinblat
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引用次数: 0
Meet Our Editorial Board—Genesis. An Interview With Thomas Schimmang, Institute for Biomedicine and Molecular Genetics, Valladolid, Spain
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2025-01-27 DOI: 10.1002/dvg.70004
Paul Trevorrow, Thomas Schimmang
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引用次数: 0
Meet Our Editorial Board—Genesis. An Interview With Paolo E. Forni, University at Albany, State University of New York, New York, USA
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2025-01-24 DOI: 10.1002/dvg.70002
Paul Trevorrow, Paolo E. Forni
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引用次数: 0
Meet Our Editorial Board—Genesis. An Interview With Yoh-suke Mukouyama, National Institutes of Health, Maryland, USA
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2025-01-24 DOI: 10.1002/dvg.70008
Yoh-suke Mukouyama, Paul Trevorrow
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引用次数: 0
Meet Our Editorial Board—Genesis. An Interview With, Sally Moody, The George Washington University School of Medicine and Health Sciences, USA 认识我们的编辑委员会--《创世纪》。专访美国乔治-华盛顿大学医学与健康科学学院莎莉-穆迪。
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2024-12-31 DOI: 10.1002/dvg.70000
Paul Trevorrow, Sally A. Moody
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引用次数: 0
Meet Our Editorial Board—Genesis. An Interview With Margot L. K. Williams, Baylor College of Medicine, Texas, USA 见见我们的编辑委员会——创世纪。采访美国德克萨斯州贝勒医学院的玛格特·l·k·威廉姆斯。
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2024-12-17 DOI: 10.1002/dvg.70001
Paul Trevorrow, Margot L. K. Williams
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引用次数: 0
Generation and Characterization of a TRIM21 Overexpressing Mouse Line TRIM21过表达小鼠品系的产生和特征描述
IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis
Pub Date : 2024-11-01 DOI: 10.1002/dvg.23616
Lisa M. Mehlmann, Tracy F. Uliasz, Siu-Pok Yee, Deborah Kaback, Katie M. Lowther

Specific removal of a protein is a key to understanding its function. “Trim-Away” utilizes TRIM21, an antibody receptor and ubiquitin ligase, for acute and specific reduction of proteins. When TRIM21 is expressed in cells, introduction of a specific antibody causes rapid degradation of the targeted protein; however, TRIM21 is endogenously expressed in few cell types. We have generated a mouse line using CRISPR to insert a conditional overexpression cassette of TRIM21 into the safe harbor site, Rosa26. These conditionally-expressing mice can be bred to a wide variety of Cre mice to target cell-specific TRIM21 overexpression in different tissues. Zp3Cre mice expressed TRIM21 protein specifically in oocytes, whereas HprtCre mice expressed the protein globally. When TRIM21-overexpressing oocytes were microinjected with specific antibodies targeting either the IP3 receptor or SNAP23, these proteins were effectively degraded. In addition, cortical neural cells from globally-overexpressing TRIM21 mice showed a dramatic reduction in IP3 receptor protein within hours after electroporation of a specific antibody. These experiments confirm the effectiveness of the Trim-Away method for protein reduction. These mice should make a valuable addition to the broader research community, as a wide range of proteins and cell types can be studied using this method.

特异性去除蛋白质是了解其功能的关键。"Trim-Away "利用抗体受体和泛素连接酶 TRIM21 来快速、特异地清除蛋白质。当 TRIM21 在细胞中表达时，引入特异性抗体会导致目标蛋白质快速降解；然而，TRIM21 在少数细胞类型中内源表达。我们利用 CRISPR 技术将 TRIM21 的条件性过表达盒插入安全港位点 Rosa26，从而产生了一种小鼠品系。这些条件表达小鼠可以与多种 Cre 小鼠杂交，从而在不同组织中实现特异性细胞 TRIM21 过表达。Zp3Cre 小鼠在卵母细胞中特异性表达 TRIM21 蛋白，而 HprtCre 小鼠则全面表达该蛋白。当向TRIM21过表达的卵母细胞显微注射靶向IP3受体或SNAP23的特异性抗体时，这些蛋白会被有效降解。此外，全局表达 TRIM21 小鼠的皮层神经细胞在电穿孔特定抗体后数小时内显示出 IP3 受体蛋白的急剧减少。这些实验证实了 Trim-Away 方法在减少蛋白质方面的有效性。这些小鼠对更广泛的研究领域来说是一个宝贵的补充，因为使用这种方法可以研究多种蛋白质和细胞类型。
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