Cold Spring Harbor Monograph Archive最新文献_第4页

17 TGF-β Family Signaling in Drosophila 果蝇TGF-β家族信号传导

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969752.50.493

George Pyrowolakis, B. Hartmann, M. Affolter

{"title":"17 TGF-β Family Signaling in Drosophila","authors":"George Pyrowolakis, B. Hartmann, M. Affolter","doi":"10.1101/087969752.50.493","DOIUrl":"https://doi.org/10.1101/087969752.50.493","url":null,"abstract":"In this chapter, we first introduce the general components of the different transforming growth factor-β (TGF-β) family signaling pathways that have been identified in Drosophila . We then describe at which steps and how the signaling pathways are regulated at different developmental stages. We highlight two topics—extracellular ligand distribution and nuclear readout of distinct levels of signaling—in which Drosophila work has provided unique insight in the past decade. For several reviews that discuss other aspects of TGF-β family signaling in Drosophila in more detail, see Affolter et al. (2001), Parker et al. (2004), and Raftery and Sutherland (1999). CORE EFFECTORS OF THE TGF-β FAMILY SIGNALING PATHWAYS IN DROSOPHILA The core components of TGF-β family signaling pathways in Drosophila show a high degree of conservation at the sequence as well as at the functional level with regard to their vertebrate counterparts, that is, the bone morphogenetic protein- (BMP) and activin-signaling pathways. In fact, several genes encoding Drosophila TGF-β family ligands or receptors were identified using polymerase chain reaction (PCR) approaches or by DNA sequence data mining starting from the sequences for mammalian members of the signaling pathway. The number of ligands and receptors encoded by the Drosophila genome is lower than that in vertebrates; seven ligand and five receptor-encoding genes have been identified (Fig. 1) (Parker et al. 2004). Three of the seven ligands, Decapentaplegic (Dpp), Screw (Scw), and Glass bottom boat (Gbb; formerly termed 60A), belong to the subfamily of BMPs, whereas dActivin and Dawdle (Daw) are related to...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"63 1","pages":"493-526"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87718689","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}

引用次数: 3

24 Adult Neurogenesis in Neurodegenerative Diseases 24神经退行性疾病中的成人神经发生

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969784.52.503

P. Brundin, J. Winkler, E. Masliah

{"title":"24 Adult Neurogenesis in Neurodegenerative Diseases","authors":"P. Brundin, J. Winkler, E. Masliah","doi":"10.1101/087969784.52.503","DOIUrl":"https://doi.org/10.1101/087969784.52.503","url":null,"abstract":"The neurodegenerative disorders parkinson’s disease (PD), Huntington’s disease (HD), Alzheimer’s disease (AD), and human immunodeficiency virus (HIV)-associated cognitive impairment (HACI) all present with a gradual loss of relatively well-defined neuronal populations. Under all of these conditions, progression is slow. In some cases, the neuropathology is relatively restricted, leaving significant parts of the nervous system unaffected. They have therefore become interesting targets for restorative therapies. One of the most exciting ideas for repair is the concept that one might be able to harness the adult brain’s endogenous capacity for cell renewal. Thus, it might be possible to direct newborn cells in the adult brain to migrate to the regions affected by the disease and there differentiate into the specific types of neurons that succumb due to the disease (Jordan et al. 2006). This concept is based on the realization that the adult mammalian brain also has the capacity to generate new neurons. The interaction between neurogenesis in the adult brain and neurodegenerative disease can also be viewed from another angle. It is conceivable that failure of a normal reparative process, i.e., adult neurogenesis, contributes to the development of the disease. Taken to its extreme, this idea has even led to the hypothesis that the symptoms in some neurodegenerative diseases may partly be the consequence of reduced adult neurogenesis, resulting in a failed replacement of dying neurons (Armstrong and Barker 2001). The objectives of this chapter are to describe neurogenesis in the adult brain and to determine to what extent it is...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"29 1","pages":"503-533"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81372091","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}

引用次数: 3

10 Aging in Mammalian Stem Cells and Other Self-renewing Compartments 哺乳动物干细胞和其他自我更新区室的衰老

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969824.51.237

Derrick J. Rossi, N. Sharpless

{"title":"10 Aging in Mammalian Stem Cells and Other Self-renewing Compartments","authors":"Derrick J. Rossi, N. Sharpless","doi":"10.1101/087969824.51.237","DOIUrl":"https://doi.org/10.1101/087969824.51.237","url":null,"abstract":"Long-lived metazoans must replace a variety of lost or consumed cells at a furious pace. For example, an adult human replaces about 1% of their 20 trillion red blood cells every day through de novo synthesis. Similarly staggering rates of cell division are at work to produce new cells in the gut, skin, and bone marrow throughout life. Additionally, certain tissues (e.g., memory lymphocytes and pancreatic β cells) possess a potential for facultative growth in the adult organism; i.e., under certain circumstances (e.g., viral infection and pregnancy), these normally quiescent cells can reenter the cell cycle to increase the mass of a given tissue through regulated proliferation. To offset the high cellular turnover rate in such tissues and avoid the onset of tissue-specific hypoplasia and atrophy, many mammalian tissues contain reservoirs of stem cells capable of generating terminally differentiated effector cell types. The unique cellular property that enables stem cells to maintain such function throughout is their ability to produce large numbers of differentiated cell types while also self-renewing themselves so that their reserves do not become depleted over time. Several lines of evidence—foremost of which is evidence indicating that aged tissues characteristically exhibit a diminished capacity to maintain homeostasis or return to homeostasis after exposure to stress—has implicated stem cell decline in the aging process. In this chapter, we review some of the evidence to support the notion that certain aspects of mammalian aging result from an age-dependent decline in the function of self-renewing stem cells, and...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"29 1","pages":"237-265"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81994302","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}

引用次数: 4

16 Genetics and Epigenetics in Adult Neurogenesis 成人神经发生的遗传学和表观遗传学

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969784.52.321

Jenny Hsieh, J. Schneider

{"title":"16 Genetics and Epigenetics in Adult Neurogenesis","authors":"Jenny Hsieh, J. Schneider","doi":"10.1101/087969784.52.321","DOIUrl":"https://doi.org/10.1101/087969784.52.321","url":null,"abstract":"Chromatin structure and function are dynamically regulated in stem cells of the brain, which serve as an important paradigm for understanding the regulatory mechanisms that transduce physiological and pathophysiological signals to the stem cell genome. In the adult vertebrate brain, the production of newborn neurons from stem cells (neurogenesis) takes place in discrete proliferation zones (niches), such as the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus (Gage 2000). A variety of signals, ranging from excitation due to locally released neurotransmitters to systemic factors or drugs that cross the blood-brain barrier, converge upon clusters of neuronal stem/progenitor cells (NSCs) residing in these niches, which are intimately associated with the cerebral microvasculature. Balanced control of self-renewal, differentiation, and survival of NSCs produces new neurons and glial cells necessary for functional homeostasis of the brain and also has an important role in brain function such as memory and learning. Moreover, as potential cancer stem cells, NSCs are suspected to be the root of brain malignancies such as glioblastoma multiforme. To become neurons, NSCs require coordinated changes in the pattern of gene expression, primarily regulated at the level of gene transcription. Epigenetic chromatin remodeling has emerged as a fundamental higher-order mechanism for fine-tuning and coordinating gene expression during neurogenesis. Important aspects of brain function such as synaptic plasticity are also governed by chromatin-remodeling enzymes, cell-type-specific transcriptional regulators, and small regulatory noncoding RNAs. Thus, signaling to the genome through diverse epigenetic regulatory mechanisms...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"18 1","pages":"321-339"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81964026","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}

引用次数: 0

32 Development of TGF-β-based Therapeutic Agents: Capitalizing on TGF-β’s Mechanisms of Action and Signal Transduction Pathways 基于TGF-β的治疗剂的开发:利用TGF-β的作用机制和信号转导途径

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969752.50.1023

C. Arteaga, J. McPherson

{"title":"32 Development of TGF-β-based Therapeutic Agents: Capitalizing on TGF-β’s Mechanisms of Action and Signal Transduction Pathways","authors":"C. Arteaga, J. McPherson","doi":"10.1101/087969752.50.1023","DOIUrl":"https://doi.org/10.1101/087969752.50.1023","url":null,"abstract":"The early publications of more than 20 years ago that described the discovery and characterization of the biological activities of TGF-β in vivo were prophetic in describing how TGF-β would ultimately serve as a therapeutic target for stimulating wound repair, preventing pathological fibrosis, and inhibiting tumor growth and metastasis (Roberts et al. 1980; Sporn et al. 1983). Since the discovery of TGF-β, other growth factors have also been identified as therapeutic targets, taken through product development, and ultimately commercialized. These have included platelet-derived growth factor (Regranex) for the treatment of diabetic foot ulcers, tumor necrosis factor antagonists (Remicade, Humira, and Enbrel) for the treatment of Crohn’s disease and rheumatoid arthritis, and a vascular endothelial growth factor (VEGF) antagonist (Avastin) for the treatment of cancer. An obvious question is why there have been no successful therapeutic agents developed based on TGF-β as a target, given the more than 20,000 papers that have been published on its important role in health and disease. Part of the answer is associated with the very complex biology of TGF-β in tissue homeostasis and the fact that it seems to be involved in numerous disease states. This biological complexity has provided a significant challenge for the scientists, clinicians, and business professionals in industry who have considered TGF-β as a therapeutic target but have struggled to determine how to develop it commercially. Another major concern has been the issue of potential toxicity associated with modulating TGF-β function in vivo. This concern was primarily based on targeted inactivation...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"21 1","pages":"1023-1061"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78685135","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}

引用次数: 0

16 TGF-β Family Signaling in Early Postimplantation Development of the Mouse TGF-β家族信号在小鼠胚胎移植后早期发育中的作用

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969752.50.461

Shigeto Miura, M. Whitman, Y. Mishina

{"title":"16 TGF-β Family Signaling in Early Postimplantation Development of the Mouse","authors":"Shigeto Miura, M. Whitman, Y. Mishina","doi":"10.1101/087969752.50.461","DOIUrl":"https://doi.org/10.1101/087969752.50.461","url":null,"abstract":"Upon implantation at embryonic day 4.5 (E4.5), the mouse embryo, a blastocyst, initiates the formation of the egg cylinder. During this process, the inner cell mass, located at the embryonic side of the blastocyst, differentiates into the epiblast and the visceral endoderm. On the opposite (abembryonic) side of the blastocyst, the mural trophoectoderm differentiates into the extraembryonic ectoderm, forming a radially symmetric structure by E5.5 (Fig. 1a,b). The future fetus is derived entirely from the epiblast. The visceral endoderm and extraembryonic ectoderm will contribute only to extraembryonic structures such as the future placenta. At the time of implantation, the early embryo is most clearly defined by this embryonic–abembryonic axis. The first sign of overt morphological asymmetry in the embryo begins with the formation of the anterior visceral endoderm, an extraembryonic tissue, at E5.5. The anterior visceral endoderm first appears at the distal tip of the egg cylinder and is defined by molecular markers such as expression of Hex . This distal region of the visceral endoderm starts to move toward the future anterior side at E5.5, and by E5.75–6.0, the distal visceral endodermal cells are located at the future anterior side of the embryo to form the anterior visceral endoderm (Rivera-Perez et al. 2003; Srinivas et al. 2004). Although the formation and anterior movement of the anterior visceral endoderm have long been thought to mark the initiation of anterior–posterior axis formation, recent findings have identified molecular asymmetries along the prospective anterior–posterior axis before the movement of the...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"1 1","pages":"461-491"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90399785","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}

引用次数: 1

28 TGF-β Signaling Pathway and Tumor Suppression 28 TGF-β信号通路与肿瘤抑制

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969752.50.889

W. Grady, S. Markowitz

{"title":"28 TGF-β Signaling Pathway and Tumor Suppression","authors":"W. Grady, S. Markowitz","doi":"10.1101/087969752.50.889","DOIUrl":"https://doi.org/10.1101/087969752.50.889","url":null,"abstract":"Transforming growth factor β (TGF-β) is the prototype member of a family of secreted proteins that include the three TGF-β isoforms (TGF-β1, TGF-β2, and TGF-β3), activins, growth and differentiation factors (GDFs), bone morphogenetic proteins (BMPs), inhibins, nodal, and anti-Mullerian hormone. These ligands all mediate biological activities in cells through binding to heteromeric receptor complexes at the cell surface that are composed of type I and type II receptors. The TGF-β family has been the subject of intense investigation since its discovery, and these studies have revealed roles for TGF-β signaling in development and cancer biology. In epithelial cells, TGF-β inhibits cell proliferation, induces apoptosis, and mediates differentiation, which suggests that this pathway has tumor-suppressor activities in epithelial tumors. Accordingly, a large body of evidence has established that elements of the TGF-β signaling pathway have a prominent role as tumor-suppressor genes in neoplasms originating from epithelial tissues, particularly gastrointestinal tract cancers. Conversely, other studies provide evidence that in certain contexts, TGF-β promotes the invasive or metastatic behavior of established cancer cells, suggesting that TGF-β paradoxically can have opposing roles in human cancers that appear to depend on the stage of the cancer. This chapter focuses on the tumor-suppressor activity of the TGF-β signaling pathway with an emphasis on the deregulation of TGF-β signaling in gastrointestinal malignancies, the organ system in which tumor-suppressor effects have been most clearly demonstrated. OVERVIEW OF TGF-β SIGNALING PATHWAY ELEMENTS AND ROLE IN TUMOR SUPPRESSION TGF-β is a multifunctional cytokine that induces growth inhibition, apoptosis, and differentiation...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"51 2 1","pages":"889-937"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90287019","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}

引用次数: 7

24 The TGF-β Family in Endothelial Cell Differentiation and Cardiovascular Development and Function TGF-β家族在内皮细胞分化和心血管发育及功能中的作用

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969752.50.761

M. Goumans, Rita L. C. Carvalho, C. Mummery, P. Dijke

{"title":"24 The TGF-β Family in Endothelial Cell Differentiation and Cardiovascular Development and Function","authors":"M. Goumans, Rita L. C. Carvalho, C. Mummery, P. Dijke","doi":"10.1101/087969752.50.761","DOIUrl":"https://doi.org/10.1101/087969752.50.761","url":null,"abstract":"Genetic studies in model organisms and humans have revealed pivotal roles for transforming growth factor-β (TGF-β) family members in cardiovascular development and maintenance. In vitro studies demonstrate that some TGF-β family members, signaling via their type I and type II receptors (Chapter 6) and intracellular Smads (Chapter 9), potently regulate the proliferation, differentiation, and migration of endothelial cells that line the entire vasculature and mural cells (vascular smooth muscle cells and pericytes) that surround the endothelial cells and aid in processes such as contraction. However, the context-dependent activities of TGF-β family members and their interactions with many cell types other than vascular cells, for example, epithelial and immune cells, have made the in vivo interpretation of the roles of TGF-β family members in vascular biology difficult. Here, we review the roles of TGF-β family members in cardiovascular development and function, and we discuss a model in which TGF-β signals via two distinct type I receptors in vascular cells. These receptors are the broadly expressed TGF-β type I receptor (TβRI, also termed ALK-5) acting via Smad2 and Smad3, and, the endothelial cell-restricted ALK-1 acting via Smad1 and Smad5. The roles of TGF-β family receptors in the development of hereditary hemorrhagic telangiectasia (HHT), primary pulmonary hypertension, and Marfan and Loeys-Dietz syndromes are also discussed. CARDIOVASCULAR DEVELOPMENT Vasculogenesis and Angiogenesis The first functional organ system to form in the embryo is the cardiovascular system. Shortly after gastrulation, when cells from the epiblast invaginate to become mesoderm, a vascular plexus develops in the visceral...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"38 1","pages":"761-788"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81426589","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}

引用次数: 0

4 Evolving Methods for the Labeling and Mutation of Postnatal Neuronal Precursor Cells: A Critical Review 出生后神经元前体细胞标记和突变的进化方法:综述

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969784.52.49

Joshua J. Breunig, P. Rakic, J. D. Macklis

{"title":"4 Evolving Methods for the Labeling and Mutation of Postnatal Neuronal Precursor Cells: A Critical Review","authors":"Joshua J. Breunig, P. Rakic, J. D. Macklis","doi":"10.1101/087969784.52.49","DOIUrl":"https://doi.org/10.1101/087969784.52.49","url":null,"abstract":"As research on postnatal neuronal progenitor, precursor, and stem cells progresses, methods of increasing sensitivity and complexity will be brought to bear in revealing how these cell types are maintained in the adult brain and how the brain adds neurons to mature circuits. Here, we review historical and current methods, such as bromodeoxyuridine (BrdU) labeling, and discuss several emerging genetic techniques, including viral vectors, small interfering RNAs (siRNAs), and inducible transgenic/knockout mice, that will be useful for the labeling and/or mutation of adult neuronal precursor cells (NPCs). As the complexity of these methods increases, so does the potential for misinterpretation of the results. The realization must be made that all methods have inherent disadvantages and confounds, preventing conclusive and definitive interpretations if used without cross-validation. We hope to give insight into how pitfalls might be avoided and provide a primer on additional methods that might be used in the pursuit of definitive results. In the past decade, a newfound appreciation has developed for the regions displaying neurogenesis in the adult mammal (Gage 2000; Lledo et al. 2006). In two regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), neurons are continually added after birth (Lois and Alvarez-Buylla 1994; Kuhn et al. 1996). In the hippocampus, neurons are born in the subgranular zone (SGZ) from Gfap + precursor cells and migrate a short distance into the granule cell layer (GCL), where they integrate, sending an axon to CA3 and receiving input at their apical dendrite (Seri et al...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"61 1","pages":"49-80"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86007925","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}

引用次数: 7

5 The Bone Morphogenetic Proteins 5骨形态发生蛋白

Cold Spring Harbor Monograph Archive Pub Date : 2008-01-01 DOI: 10.1101/087969752.50.121

T. Katagiri, T. Suda, K. Miyazono

{"title":"5 The Bone Morphogenetic Proteins","authors":"T. Katagiri, T. Suda, K. Miyazono","doi":"10.1101/087969752.50.121","DOIUrl":"https://doi.org/10.1101/087969752.50.121","url":null,"abstract":"Bone morphogenetic proteins (BMPs) have critical roles in skeletal development by regulating the proliferation, differentiation, and apoptosis of many types of cells. Molecular cloning of BMPs and identification of molecules homologous to them have shed light on the novel functions of BMPs in vertebrates as well as in invertebrates, including Drosophila and nematodes. In this chapter, we describe biochemical properties and biological activities of BMPs; we focus, in particular, on the cell differentiation induced by BMPs. Although BMPs are now known to be multifunctional factors in vertebrates and invertebrates, they were originally discovered and identified as a bone-inducing activity in bone matrix in 1965. Marshall R. Urist (1965) first prepared demineralized bone by treating bone with hydrochloric acid and then implanting the demineralized bone in muscular tissues. A few weeks after transplantation, he found that new cartilage and bone tissues with bone marrow had been ectopically formed in muscular tissue (Urist 1965). These findings clearly indicated that the demineralized bone matrix contained unknown bioactive substance(s) capable of inducing differentiation of bone-forming cells in muscular tissues. This ectopic bone-inducing activity was subsequently named “bone morphogenetic protein,” because it disappeared after trypsin digestion (Urist and Strates 1971). However, all attempts to isolate and identify BMP were unsuccessful for more than 20 years after Urist’s original findings because of the difficulty in isolating BMP from bone matrix. BMP activity was water insoluble and could be extracted from demineralized bone matrix with protein denaturants (Urist and Strates 1971; Sampath and Reddi 1981; Yoshikawa et...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"69 1","pages":"121-149"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89143805","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}

引用次数: 43