{"title":"3 Processing of Yeast Cytoplasmic and Mitochondrial Precusor tRNAs","authors":"A. Hopper, N. Martin","doi":"10.1101/087969365.21B.99","DOIUrl":"https://doi.org/10.1101/087969365.21B.99","url":null,"abstract":"I. INTRODUCTION The purpose of this chapter is to describe the processing of pre-tRNAs in yeast, integrating information on processing in the nucleus and mitochondria. Precursor tRNAs produced from nuclear genes and mitochondrial genes have the same general requirements: Various activities are needed to remove 5´leaders and 3´trailers, to add the CCA end, and to catalyze numerous base modifications (Fig. 1). In addition, a subset of nuclear pre-tRNAs have introns that must be removed, although no such activities are required for the biogenesis of any yeast mitochondria1 tRNA. Some yeast nuclear tRNA genes are transcribed together in dimeric pairs (Schmidt et al. 1980), and mitochondria1 tRNAs are transcribed with other tRNAs (Palleschi et al. 1984b; Martin et al. 1985b; Bardonne et al. 1987; Francisci et al. 1987), with ribosomal RNAs (Osinga et al. 1984; Palleschi et al. 1984a), with mRNAs (Miller et al. 1983; Zassenhaus et al. 1984), or with the RNasc P RNA (Shu and Martin 1991). Although these polycistronic transcripts are processed by a variety of activities, only those directly involved in tRNA recognition and processing are considered here. We have not attempted to review tRNA gene organization or transcription, as these topics have been covered elsewhere. The reader is referred to Guthrie and Abelson (1982) for a review of yeast nuclear tRNA genes, to Thuriaux and Sentenac (this volume) for a review of nuclear tRNA gene transcription, and to Tzagoloff and Myers (1986) for a review of mitochondria1 tRNA genes. In general, we have...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"1 1","pages":"99-141"},"PeriodicalIF":0.0,"publicationDate":"2009-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79890347","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":"13 Extracellular Matrix in the Skeleton","authors":"F. Ramirez","doi":"10.1101/087969825.53.341","DOIUrl":"https://doi.org/10.1101/087969825.53.341","url":null,"abstract":"The extracellular matrix (ECM) is a highly heterogeneous amalgam of multidomain molecules that are intimately involved in the development, growth, function, and homeostasis of every organ system, including the skeleton. Similar to other connective tissues, bone and cartilage matrices consist of collagens, proteoglycans (PGs), and noncollagenous (NC) proteins, in addition to including enzymes involved in matrix assembly and degradation. That the vast majority of these molecules are also found in other tissues indicates that relative differences in ECM composition specify form and function at discrete anatomical locations of the developing and adult skeleton. This chapter provides an introduction to ECM composition and organization in the skeleton, and a brief review of the contribution of selected matrix molecules to bone formation and remodeling that is mostly based on genetic evidence from loss-of-function studies in mice. Similar topics are also covered in other chapters of this book, and a number of excellent reviews are available that describe various aspects of ECM biology in greater detail. ECM COMPOSITION AND ORGANIZATION Collagens Collagens are the most abundant and diverse components of the connective tissue (Mecham 1998; Birk and Bruckner 2005). All collagens possess at least one triple helical (or collagenous [COL]) domain and NC domains of variable length and composition. Most collagens give rise to morphologically diverse suprastructures that are also referred to as molecular composites because they include additional collagens and NC proteins (Birk and Bruckner 2005). For example, tissue-specific organization of collagen I or II networks is largely regulated by copolymerization with...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"43 1","pages":"341-353"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79320606","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":"8 Role of Growth Factors in Bone Development and Differentiation","authors":"S. Fujimori, D. Kostanova-Poliakova, C. Hartmann","doi":"10.1101/087969825.53.219","DOIUrl":"https://doi.org/10.1101/087969825.53.219","url":null,"abstract":"Bone is a form of highly specialized mineralized connective tissue that provides strength to the skeletal system of higher vertebrates, while still retaining a certain degree of elasticity. The bone matrix is produced by osteoblasts, a cell-type that develops locally from mesenchymal precursors, and is resorbed by the osteoclast, a cell-type of hematopoietic origin. A few elements, such as the flat bones of the skull and part of the clavicle, are formed by the process of intramembranous ossification, whereby osteoblasts differentiate directly from cells within mesenchymal condensations. In contrast, the majority of skeletal elements are formed by endochondral ossification involving the remodeling of initial cartilaginous templates into bony tissue. The latter process requires controlled maturation of chondrocytes from proliferating and prehypertrophic to hypertrophic chondrocytes, as well as signaling from the prehypertrophic cells to the surrounding cells in the perichondrium, resulting in a regional induction of osteoblast differentiation. Osteoblasts start to differentiate in the periosteum, a region flanking prehypertrophic and hypertrophic chondrocytes. The typical appearance of one end of a juvenile long bone still containing a cartilaginous growth plate is shown in Figure 1. Recent lineage studies suggest that osteoblasts and chondrocytes share a common precursor in the limb. Thus, especially in the limb, the activation and/or inhibition of distinct signaling pathways is necessary in order to coordinate the differentiation of neighboring cells into distinct cell lineages and to synchronize their maturation. This chapter focuses on genetic and molecular studies elucidating the role of different locally produced growth factors during embryonic...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"538 1","pages":"219-261"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79616297","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":"5 Transcriptional Control of Chondrocyte Differentiation","authors":"B. Crombrugghe, H. Akiyama","doi":"10.1101/087969825.53.147","DOIUrl":"https://doi.org/10.1101/087969825.53.147","url":null,"abstract":"Bone formation occurs through two distinct processes. Most skeletal, elements form by endochondral ossification, which involves a cartilage intermediate. The other skeletal elements, which mainly include craniofacial bones, are formed by a process of intramembranous ossification, whereby bones form directly from mesenchymal condensations without involvement of a cartilage intermediate. In addition to forming the templates for the development of endochondral bones, cartilage is also present as a permanent connective tissue at the ends of bones (articular cartilages) and in ear, nose, and throat tissues. Chondrogenesis is a multistep process that begins with the commitment of mesenchymal cells to a chondrogenic cell lineage (Fig. 1). These cells then aggregate into condensations that prefigure the future shape of endochondral bones. Cells in these mesenchymal condensations overtly differentiate into chondrocytes and produce a characteristic cartilage extracellular matrix (ECM). These cells then undergo several more changes. The first is a unidirectional proliferation that results in parallel columns of dividing cells that fuel the longitudinal growth of bones. In contrast to the overtly differentiated chondrocytes, which are round cells, the proliferating chondrocytes in these parallel columns have a flat morphology. These cells then exit the cell cycle, gradually change their genetic program, and become prehypertrophic and then hypertrophic chondrocytes. The most mature hypertrophic chondrocytes, which acquire the ability to mineralize their ECM, later die by apoptosis. In endochondral skeletal elements, first a thin layer of mesenchymal cells on the periphery of the condensations forms the perichondrium, which subsequently develops into the periosteum. Cells in the...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"175 1","pages":"147-170"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79752643","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":"7 Transcriptional Control of Osteoblast Differentiation","authors":"G. Karsenty","doi":"10.1101/087969825.53.205","DOIUrl":"https://doi.org/10.1101/087969825.53.205","url":null,"abstract":"In contrast with chondrocyte differentiation, where all maturational stages are morphologically marked as well as spatially distinguishable within the growth plate, osteoblast differentiation is not marked by phenotypic changes in vivo, and osteoblasts in culture are, and remain throughout their differentiation, similar to fibroblasts. This absence of morphological features implies that one has to rely on gene expression studies to assess osteoblast differentiation. However, here again, the osteoblast has a poorly specific genetic program. Most of the proteins expressed by this cell type are also expressed in other cells, notably in fibroblasts. Another feature of osteoblast differentiation is that its embryonic layout is more complex than the events taking place once the skeleton is formed. Indeed, the developmental process by which osteoblast precursors first appear in the bone collar, begin to differentiate and then migrate within the core of the forming skeletal element along with invading blood vessels, is not observed anymore once the bones are formed. In the mature skeleton osteoblast, progenitor cells are spread out within the bone marrow and differentiate in situ. These two particularities explain for the most part why identifying the key transcriptional events required for osteoblast differentiation and function has been slower than for other cell types. However, in the last decade, these limitations have been overcome due to a combination of molecular efforts and genetic studies in mice and humans. This chapter summarizes our current knowledge about the transcriptional control of osteoblast differentiation and function (Fig. 1). CONTROL OF OSTEOBLAST DIFFERENTIATION BY RUNX2...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"79 1","pages":"205-217"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88581811","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 Craniofacial Patterning","authors":"N. Douarin, S. Creuzet","doi":"10.1101/087969825.53.117","DOIUrl":"https://doi.org/10.1101/087969825.53.117","url":null,"abstract":"HISTORICAL BACKGROUND One of the most striking characteristics about the craniofacial bones is that, contrary to the rest of the vertebrate skeleton, they are not entirely of mesodermal origin. Embryological studies, which started at the end of the 19th century with the observations of Kastschenko (1888, for selacians) and Goronovitch (1892, 1893, for teleosts and birds), have established that mesenchymal cells can arise, not only from the mesodermal, but also from the ectodermal germ layer. During this period, Julia Platt was the first to propose in 1893 that ectoderm contributed not only to the mesenchyme, but also to the cartilage of the visceral arches and to the dentine of the teeth in the mud puppy, Necturus . This derivation of mesenchyme, bones and cartilages from the ectoderm, was shown to occur via a transient structure, the Neural Crest (NC), which was first described in the chick embryo by the German Histologist Wilhem His in 1868. These observations contradicted the germ layer theory first put forward by Christian Heinrich Pander (1817), who described the formation of three layers of cells from the chick blastoderm. Later, Karl von Baer (1828) extended Pander’s findings to all vertebrate embryos. In 1849, Thomas Huxley generalized the presence of germ layers to invertebrates and the terms ectoderm, mesoderm , and endoderm were first used to designate the vertebrate germ layers by Ernst Haeckel in 1874, in the context of the Gastrea concept. The observation that formation of germ layers precedes organ morphogenesis and cellular differentiation was followed by...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"23 1","pages":"117-145"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83651908","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":"2 Developmental Patterning of the Limb Skeleton","authors":"Kimberly L. Cooper, C. Tabin","doi":"10.1101/087969825.53.19","DOIUrl":"https://doi.org/10.1101/087969825.53.19","url":null,"abstract":"The vertebrate skeleton is composed of approximately 200 bones, ranging in shape and size from the delicate bones of the mammalian inner ear to the robust femur. Each individual bone forms in a precise location and orientation with respect to its neighbors and in relation to force generating and transmitting tissues—the muscles, tendons, and ligaments. The appropriate structure of the bones is essential for function of the skeleton to support and move the body, and depends on an array of molecular cues that pattern their formation early in development. Our knowledge of developmental mechanism patterning all tissues and organs of the body, including the skeleton, is largely derived from experiments using two model systems—chick and mouse embryos. While aspects of patterning the craniofacial and axial skeletal elements have been elucidated, development of the bones of the limbs is particularly well understood. The limbs are easily accessible for embryological manipulation and are expendable for the survival of prenatal animals, allowing for analysis of late developmental phenotypes after genetic or surgical perturbation. The developing limb bud has therefore become an important model for the investigation of cellular and molecular mechanisms that pattern the tissues that give rise to bones. The tetrapod limb is of additional interest from an evolutionary perspective because it is a conserved but malleable structure whose adaptive variations in form increase an animal’s fitness in different ecological niches—by promoting mobility, aiding in the acquisition of food, fighting against or escaping from predators, and assisting in reproduction...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"69 1","pages":"19-39"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81115380","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":"3 Patterning and Differentiation of the Vertebrate Spine","authors":"J. Chal, O. Pourquié","doi":"10.1101/087969825.53.41","DOIUrl":"https://doi.org/10.1101/087969825.53.41","url":null,"abstract":"One of the most striking features of the human spine is its periodic organization. This so-called “segmental” arrangement of the vertebrae along the anteroposterior body axis is established during embryonic development. Structures called somites, which contain the precursors of the vertebrae, form in a rhythmic fashion at the posterior end of the embryo during the process of somitogenesis. Somites are sequentially added to the growing axis, thus establishing the characteristic periodic pattern of the future vertebral column. The primary segmentation of the vertebrate embryo displayed by somitic organization also underlies much of the segmental organization of the body, including muscles, nerves, and blood vessels. In amniotes, somites are the major component of the paraxial mesoderm that form bilaterally along the nerve cord as a result of primitive streak and tail bud regression during body axis formation. Somites bud off from the anterior presomitic mesoderm (PSM) as epithelial spheres surrounding a core of mesenchymal cells called the somitocoele. The dorsal portion of the somite remains epithelial and forms the dermomyotome, which differentiates into muscle and dermis while its ventral moiety undergoes an epithelio-mesenchymal transition, leading to the formation of the sclerotome. The sclerotome gives rise to the skeletal elements of the vertebral column: the vertebrae, ribs, intervertebral disks, and tendons. Most of our understanding of amniote somitogenesis at the morphogenetic and molecular levels results from studies involving the chicken ( Gallus gallus ) and the mouse ( Mus musculus ). In this chapter, we essentially focus on the patterning and development of the spine in...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"142 1","pages":"41-116"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76629177","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":"6 Growth Factors and Chondrogenesis","authors":"H. Kronenberg, A. McMahon, C. Tabin","doi":"10.1101/087969825.53.171","DOIUrl":"https://doi.org/10.1101/087969825.53.171","url":null,"abstract":"Chondrogenesis, whether during the formation of cartilage models during endochondral bone formation, longitudinal and apositional growth, maintenance of the articular surfaces, or during repair and healing, is a carefully orchestrated multistep process. As such, regulation of this process requires the interplay of a large number of factors, including inductive cues from surrounding tissues, intercellular signals emanating from within the cartilage itself, and intrinsic factors within the chondrocytes. Indeed, intrinsic and extrinsic regulation are intimately related to one another. In response to specific sets of growth factors, cells at various stages of chondrogenic differentiation activate expression of unique sets of transcription factors committing them to, and defining, particular cell states. In turn, a consequence of the expression of these transcription factors is the regulated production of stage-specific secreted proteins that feedback on other chondrogenic cells. Of equal importance, the transcriptional state of cells in the chondrogenic pathway determines their ability to respond to specific factors and the nature of their response. These intrinsic and extrinsic factors are thus components of a complex integrated network, a fact that must be borne in mind while considering any one aspect of chondrogenic regulation. Nonetheless, given the incomplete nature of our current understanding of chondrogenesis, and the complexity of the problem, it is perhaps easiest to organize a discussion of chondrogenesis by considering inductive factors and intrinsic regulation individually. This review focuses on the secreted proteins and signal transduction systems that regulate various aspects of chondrogenesis, while the transcription factors upstream and downstream of these...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"117 1","pages":"171-203"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79417132","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}