{"title":"15 Regulation of the Smad Pathway by Signaling Cross-Talk","authors":"K. Luo","doi":"10.1101/087969752.50.439","DOIUrl":"https://doi.org/10.1101/087969752.50.439","url":null,"abstract":"The TGF-β family of cytokines regulates a wide array of biological activities in various cell types and at different developmental stages. Smad proteins are critical mediators of TGF-β, BMP (bone morphogenetic protein), and activin signaling (Itoh et al. 2000; Moustakas et al. 2001; Derynck and Zhang 2003; Shi and Massague 2003). Upon phosphorylation by the active type I receptor kinase, R-Smads (receptor-activated Smads) form a heteromeric complex with the co-Smads (common-mediator Smads) and translocate into the nucleus, where they interact with sequence-specific DNA-binding cofactors and transcriptional coactivators or corepressors to regulate the expression of target genes (see Chapter 9). This pathway is integrated into the overall signaling network in the cell through cross-talk with other signaling pathways at multiple levels, which depend on the specific physiological context. These cross-talk activities play important roles in the regulation of various biological responses induced by TGF-β, BMP, or activin. In this chapter, the cross-talk of Smads with Wnt signaling, Notch signaling, MAP kinase signaling, phosphatidylinositol-3 (PI3) kinase-Akt, protein kinase C (PKC), and Jak-Stat pathway will be discussed. CROSS-TALK WITH WNT SIGNALING PATHWAY Combinatorial signaling often occurs in early embryos to allow overlapping signaling pathways to specify different territories and cell fates. The Wnt, BMP and TGF-β, and the Notch signaling pathways are integrated in this combinatorial signaling and often function in a synergistic or antagonistic manner to regulate vertebrate development. The Wnt signaling pathway has an important role in cell fate determination, self-renewal and maintenance of stem cell and early progenitor cells at...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"40 1","pages":"439-459"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86274079","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":"4 Activins and Inhibins","authors":"E. Wiater, W. Vale","doi":"10.1101/087969752.50.79","DOIUrl":"https://doi.org/10.1101/087969752.50.79","url":null,"abstract":"Activins and the structurally and functionally related inhibins belong to the transforming growth factor-β (TGF-β) family of growth factors. Activins and inhibins have central roles in regulating follicle-stimulating hormone (FSH) release and in coordinating reproductive physiology. Inhibins function as classical endocrine hormones, whereas both activins and inhibins have localized autocrine and paracrine roles. Activins have additional functions outside of the reproductive systems as regulators of cell growth and differentiation, particularly in response to injury and inflammation. This chapter discusses the mechanisms involved in activin and inhibin activities and the roles of these factors in reproductive and other tissues. STRUCTURES AND SYNTHESIS OF ACTIVINS AND INHIBINS A hormone termed “inhibin” was proposed to exist in 1932 (McCullagh 1932). Inhibin was defined as a nonsteroidal, water-soluble factor in gonadal extracts that prevents stereotypical changes in the morphology of the pituitary that appeared after castration. After the identification of the pituitary cell types and their corresponding hormones, this definition was refined: Inhibin exerts a direct effect on pituitary gonadotrope cells, leading to a specific suppression of FSH release, without altering the release of luteinizing hormone (LH) (de Kretser et al. 1988; Vale et al. 1988). Biochemical purification of inhibin was undertaken using this activity on pituitary cells as an assay. Secretions of various gonadal fluids were found to be rich sources of inhibin and were thus used as source material for purification. Inhibins—and in the process, activins—were eventually purified to apparent homogeneity from these sources based on their effects on FSH...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"39 1","pages":"79-120"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89707396","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":"22 Computational Modeling of Adult Neurogenesis","authors":"J. Aimone, Laurenz Wiskott","doi":"10.1101/087969784.52.463","DOIUrl":"https://doi.org/10.1101/087969784.52.463","url":null,"abstract":"One of the most intriguing differences between adult and developmental neurogenesis is that in the adult brain, new neurons are integrating into already-developed, functioning circuits. Newborn neurons develop highly complex neuronal morphology—an impressive feat, considering that the extracellular signaling environment (thought to be important during development) is considerably different in the adult. Adult neurogenesis has been observed in most animal species, both in the normal course of life and in response to injury in many nonmammals. The fact that adult neurogenesis is essentially limited to two regions in mammalian brains suggests that the addition of new neurons to these regions (the olfactory bulb [OB] and dentate gyrus [DG]) is of particular importance. Although the function of regenerative neurogenesis is self-evident, the purpose for lifelong neurogenesis remains unclear. There are several reasons why taking a computational modeling approach has potential. One is that any effect of adding new neurons will first be manifested computationally in the network and will only then be observed behaviorally. Modeling can permit the observation of an effect that otherwise would go unseen in standard behavioral assays. This provides a framework by which new predictions can be made that can be specifically tested experimentally. Furthermore, a well-developed computational model or theory can be altered in a manner that is impractical or impossible in animal models, such as increasing the rate of neurogenesis by tenfold or studying the effects of neurogenesis in nonneurogenic areas. Finally, modeling the computational aspects of a system often helps focus future experiments,..","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"49 1","pages":"463-481"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79895270","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":"Preface/Front Matter","authors":"R. Derynck, K. Miyazono","doi":"10.1101/087969752.50.I","DOIUrl":"https://doi.org/10.1101/087969752.50.I","url":null,"abstract":"It has been close to 30 years since the discovery of transforming growth factors as secreted proteins with the ability to induce a reversible transformed phenotype under some cell culture conditions. Not surprisingly, these findings were very skeptically received, because around that time, oncogenes were being discovered as genes encoding cell-autonomous proteins that genetically endowed the cells to behave and function as cancer cells. The discovery of transforming growth factors led to the concept of autocrine control of cell transformation and, later, of cell differentiation and function. Following its discovery, transforming growth factor-β (TGF-β) was shown to have key functions in a variety of cell and tissue contexts, most notably in cell proliferation and differentiation, development, malignant transformation, and cancer progression. In fact, TGF-β was rediscovered several times as secreted proteins with diverse activities, for example, cartilage-inducing factor, glioblastoma-derived T-cell suppressor factor (GTsF), and growth inhibitor from BSC-1 cells. Following the elucidation of the polypeptide sequence of TGF-β1, it became rapidly apparent through cDNA cloning that there is a family of structurally related proteins that together form the TGF-β family that functions in all metazoans from Planaria and nematodes to Drosophila and vertebrates. Activins and inhibins were discovered as hormones that act on pituitary gonadotrope cells and regulate the release of follicle-stimulating hormone. Research on bone morphogenetic proteins (BMPs) was launched by the observation that the demineralized bone matrix contains bioactive proteins capable of inducing bone and cartilage formation in muscular tissues. Purification of these proteins and subsequent cDNA cloning","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81212039","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":"31 TGF-β and Fibrosis","authors":"E. Böttinger","doi":"10.1101/087969752.50.989","DOIUrl":"https://doi.org/10.1101/087969752.50.989","url":null,"abstract":"Fibrosis is a cardinal feature of most chronic degenerative diseases and may affect virtually every tissue and organ system. The fibrotic response has been characterized as inappropriate repair by connective tissue resulting in scarring, associated with loss of normal tissue architecture and function. The degeneration of functional cell types and accumulation of mesenchymal cells and extracellular matrix (ECM) typically progress slowly over several years, resulting eventually in organ failure. Fibrotic conditions, irrespective of their diverse etiology, anatomic location, and natural history, share common pathogenetic features: excessive secretion and activation of profibrotic cytokines, influx of inflammatory cells, loss of differentiated epithelial cells, expansion and activation of fibroblastoid cells, and ECM synthesis and organization (Border and Noble 1994; Friedman 2003). Because these features are also observed in normal wound healing, it has been proposed that fibrosis can be conceptualized as “healing without end” or “the dark side of tissue repair” (Border and Noble 1994). Disease-oriented studies in experimental models and human disease universally demonstrate alterations of transforming growth factor-β (TGF-β) expression in tissues affected by fibrosis, including pulmonary fibrosis (Hoyt and Lazo 1989; Raghu et al. 1989), hepatic fibrosis (Czaja et al. 1989; Nakatsukasa et al. 1990), renal fibrosis (Border et al. 1990a; Okuda et al. 1990; Coimbra et al. 1991; Jones et al. 1991), ocular fibrosis (Connor et al. 1989), cardiac fibrosis (Chua et al. 1991), radiation fibrosis (Anscher et al. 1990), and systemic sclerosis and fibrotic skin diseases (Peltonen et al. 1990; Falanga and Julien 1990). TGF-β is the prototypical...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"03 1","pages":"989-1022"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86272811","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":"30 Adult Hippocampal Neurogenesis in Natural Populations of Mammals","authors":"I. Amrein, H. Lipp, R. Boonstra, J. Wojtowicz","doi":"10.1101/087969784.52.645","DOIUrl":"https://doi.org/10.1101/087969784.52.645","url":null,"abstract":"This chapter is based on the premise that if we are to acquire a deep understanding of adult neurogenesis—what it is selected for (i.e., its functional and adaptive significance), what causes it to go up or down (e.g., species constraints, reproductive hormones, seasonality, stress, and environmental conditions), and why it declines with age—the research must ultimately be grounded on an evolutionary and ecological foundation. The aphorism of Dobzansky (1973) is particularly apropos: “Nothing in biology makes sense, except in the light of evolution.” Thus, simply focusing on humans and those laboratory species we select for will not be sufficient to crack this enigma. Such a deep understanding may also aid in ameliorating debilitating aspects of the human condition after injury or in disease. This chapter advocates for studies that deal with animals that live out their lives in the context of what they were actually selected to do. Given the paucity of studies from nature, it raises more questions than it answers. It focuses largely on mammals. The formation of new neurons in adult animals is a highly conserved trait in vertebrates, occurring in all groups, from fish to mammals in various brain regions. It is linked to a diversity of life history traits such as lifelong body growth in fishes and rats and seasonal variation in song control nuclei in birds (Lindsey and Tropepe 2006). In mammals, adult neurogenesis occurs physiologically in two germinal areas: the subventricular zone (SVZ), which lies adjacent to the lateral wall of...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"49 1","pages":"645-659"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84168229","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":"19 Regulation of Adult Neurogenesis by Neurotransmitters","authors":"M. Jang, Hongjun Song, G. Ming","doi":"10.1101/087969784.52.397","DOIUrl":"https://doi.org/10.1101/087969784.52.397","url":null,"abstract":"Active adult neurogenesis occurs from neuronal progenitor cells (NPCs) in discrete regions of the adult mammalian central nervous system (CNS) (Abrous et al. 2005; Ming and Song 2005; Lledo et al. 2006). The generation of nascent neurons from NPCs in the intact adult CNS is restricted to the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) (Alvarez-Buylla and Lim 2004). Outside of these two regions, proliferating NPCs normally generate only glia cells, but they appear to be able to give rise to neurons after insults (Emsley et al. 2005). Accumulative evidence suggests that continuous neuronal production in the adult brain under physiological conditions is involved in specific brain functions, such as olfaction, learning, and memory (Kempermann et al. 2004a). On the other hand, neural production of NPCs under pathological conditions may contribute to brain repair (Emsley et al. 2005). Functional integration of nascent neurons is achieved by progression through sequential developmental steps that resemble embryonic and fetal neurogenesis, from proliferation and fate specification of NPCs, to differentiation, migration, axonal/dendritic development, and synaptic integration of newborn neurons (Ming and Song 2005). In contrast to developing neurogenesis, adult neurogenesis arises from a significantly different environment and proceeds with concurrent activities of mature neurons within the existing circuit. Adult neurogenesis, a striking form of structural plasticity in the intact adult CNS, is dynamically regulated by many physiological and pathological stimuli (Abrous et al. 2005; Ming and Song 2005). For example, environmental enrichment (Kempermann...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"26 1","pages":"397-423"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81287476","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":"23 TGF-β Family in Epithelial Development","authors":"Nina M. Muñoz, W. Grady","doi":"10.1101/087969752.50.725","DOIUrl":"https://doi.org/10.1101/087969752.50.725","url":null,"abstract":"Transforming growth factor-β (TGF-β) family members, such as TGF-βs, activins, inhibins, bone morphogenetic proteins (BMPs), and nodal, have critical roles in the development of epithelial structures in a variety of organs, including the skin, lung, mammary gland, and gastrointestinal tract. These organs consist of cell populations derived from the ectoderm, mesoderm, and/or endoderm. The differentiation and function of cells derived from each of these three germ layers are regulated by TGF-β family members through autocrine and paracrine mechanisms, thus positioning these proteins as key regulators of organogenesis (Weaver et al. 1999; Schier 2003). The effects of TGF-β proteins are subject to autoregulatory interactions that control the activities and propagation of signaling. These effects are restricted temporally and spatially by the expression of ligands, receptors, and soluble ligand inhibitors and postreceptor signaling proteins. The roles of TGF-β family proteins in epithelial development have been deduced primarily from studies of the mammary gland, lung, and gastrointestinal tract, which are derived from the endoderm and mesoderm, and of the skin, which is from ectodermal and mesodermal origin. Furthermore, study of the epidermal appendages, specifically the teeth, hair, and feathers, has contributed to our understanding of the role of TGF-β family members in epithelial development and epithelial–mesenchymal interactions. This chapter discusses the roles of TGF-β family proteins and TGF-β signaling mediators in epithelial development in these organ systems. TGF-β family members affect the epithelium both during embryonic development and in the adult organism. In embryonic development, TGF-β, activin, and BMP-4 regulate some of...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"44 1","pages":"725-759"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89518941","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":"12 Adult Neurogenesis: Similarities and Differences in Stem Cell Fate, Proliferation, Migration, and Differentiation in Distinct Forebrain Regions","authors":"D. Lie, M. Götz","doi":"10.1101/087969784.52.227","DOIUrl":"https://doi.org/10.1101/087969784.52.227","url":null,"abstract":"Self-renewal and proliferation of neural stem cells, neuronal fate determination of uncommitted precursors, and migration of neuroblasts are the earliest steps in adult neurogenesis. Self-renewing divisions are required for the maintenance of the stem cell pool, which ensures that neurogenesis continues throughout the lifetime of the organism. Instruction of the stem cell progeny to adopt a neuronal fate is a common feature between the neurogenic niches, yet it is likely that local instructive programs are distinct given that different neuronal phenotypes are generated in neurogenic areas. Finally, immature neurons are born distant from their future location. Thus, migration of the newborn neurons must be tightly regulated to ensure the proper integration of new mature neurons into the neuronal network. In this chapter, we discuss these processes from a functional perspective and summarize current knowledge regarding their cellular and molecular regulation. Stem cells are defined as cells with the potential to generate differentiated progeny and the potential to undergo unlimited self-renewing divisions (Weissman et al. 2001). In the hematopoietic system, the existence of adult stem cells has been proven through assays, in which a single adult cell and its progeny have been repeatedly challenged to reconstitute the entire hematopoietic system in serial transplantations to lethally irradiated organisms (Weissman et al. 2001). The reconstitution of the entire hematopoietic system demonstrates the multipotentiality of the transplanted cell, whereas their ability to do so in serial transplantations indicates the self-renewal of the initially transplanted cell. Such stringent stem cell assays are presently not available...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"149 1","pages":"227-265"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79437767","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}
R. Weindruch, R. Colman, V. Pérez, Arlan Richardson
{"title":"15 How Does Caloric Restriction Increase the Longevity of Mammals","authors":"R. Weindruch, R. Colman, V. Pérez, Arlan Richardson","doi":"10.1101/087969824.51.409","DOIUrl":"https://doi.org/10.1101/087969824.51.409","url":null,"abstract":"The classic study by McCay et al. in 1935 showed that one could increase the life span of rats by reducing their food consumption. Since this initial observation, numerous laboratories have confirmed these results and have shown that reducing food consumption 30–50% (without malnutrition) consistently increases both the mean and maximum life spans of laboratory rodents (Weindruch and Walford 1988; Masoro 2005). Caloric restriction is also able to oppose the development of diverse age-associated diseases arising in laboratory rodents, including many types of cancer, diabetes, and renal disease (Weindruch and Walford 1988). This paradigm has been termed caloric restriction, dietary restriction, or food restriction. In this chapter, we use the term caloric restriction (CR) because the decreased intake of total calories appears to be responsible for the increased life span of rodents (Masoro 2005), rather than the reduction in a specific nutrient, such as dietary protein or fat (Iwasaki et al. 1988; Masoro et al. 1989). It is important to note that the effect of CR on longevity is not limited to rodents, as it increases the life span of a variety of invertebrates, e.g., yeast, Caenorhabditis elegans , and Drosophila (Min and Tatar 2006), as well as of dogs (Kealy et al. 2002). In this review chapter, we focus on what currently is known of the biological mechanism responsible for the life-extending action of CR in mammals, specifically laboratory rodents and nonhuman primates. LABORATORY RODENTS Since the seminal observation by McCay et al. in 1935, CR has been shown...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"33 1","pages":"409-425"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73115513","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
