The Physical and Biochemical Properties of the Extracellular Matrix Regulate Cell Fate.
We present examples describing how the extracellular matrix functions as a highly complex physical and chemical entity that regulates tissue organization and cell behavior through a dynamic and reciprocal dialogue with the cellular constituents of the tissue. We suggest that the extracellular matrix not only transmits cellular and tissue-level force to shape development and tune cellular activities that are key for coordinated tissue behavior, but that it is itself remodeled such that it temporally evolves to maintain the integrated function of the tissue. Accordingly, we argue that perturbations in extracellular matrix co...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Muncie JM, Weaver VM Tags: Curr Top Dev Biol Source Type: research

Collagen Fibril Assembly and Function.
Abstract Collagen fibrils are the major mechanical component in the extracellular matrix of a broad range of multicellular animals from echinoderms to vertebrates where they provide a stable framework for tissues. They form the key tension-resisting element of a complex fiber-composite system that has a tissue-specific hierarchical structure linked to mechanical demands. Remarkably, these tissues are self-maintaining and avoid fatigue failure over the lifetime of the animal. Collagen fibrils can assemble spontaneously from purified solutions of collagen molecules. In developing tissues, however, in addition to the...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Holmes DF, Lu Y, Starborg T, Kadler KE Tags: Curr Top Dev Biol Source Type: research

Basement Membranes in Development and Disease.
Abstract The basement membrane is a thin but dense, sheet-like specialized type of extracellular matrix that has remarkably diverse functions tailored to individual tissues and organs. Tightly controlled spatial and temporal changes in its composition and structure contribute to the diversity of basement membrane functions. These different basement membranes undergo dynamic transformations throughout animal life, most notably during development. Numerous developmental mechanisms are regulated or mediated by basement membranes, often by a combination of molecular and mechanical processes. A particularly important p...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Sekiguchi R, Yamada KM Tags: Curr Top Dev Biol Source Type: research

Extracellular Determinants of Arterial Morphogenesis, Growth, and Homeostasis.
Abstract The extracellular matrix (ECM) is a highly heterogeneous mixture of macromolecules capable of self-assembling into tissue-specific suprastructures that constitute the architectural elements supporting organ function. Contrary to the traditional view of being a static scaffold that supports tissue integrity along with cell adhesion and migration, the ECM is an inherently dynamic system that specifies cellular function and defines the limits and patterns of tissue organization. Throughout evolution, the composition and organization of the ECM have changed to accommodate basic and new tissue functions, both ...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Mecham RP, Ramirez F Tags: Curr Top Dev Biol Source Type: research

Structure, Function, and Development of the Tectorial Membrane: An Extracellular Matrix Essential for Hearing.
Abstract The tectorial membrane is an extracellular matrix that lies over the apical surface of the auditory epithelia in the inner ears of reptiles, birds, and mammals. Recent studies have shown it is composed of a small set of proteins, some of which are only produced at high levels in the ear and many of which are the products of genes that, when mutated, cause nonsyndromic forms of human hereditary deafness. Quite how the proteins of the tectorial membrane are assembled within the lumen of the inner ear to form a structure that is precisely regulated in its size and physical properties along the length of a to...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Goodyear RJ, Richardson GP Tags: Curr Top Dev Biol Source Type: research

Extracellular Matrix (ECM) and the Sculpting of Embryonic Tissues.
Abstract Extracellular matrices (ECMs) are structurally and compositionally diverse networks of collagenous and noncollagenous glycoproteins, glycosaminoglycans, proteoglycans, and associated molecules that together comprise the metazoan matrisome. Proper deposition and assembly of ECM is of profound importance to cell proliferation, survival, and differentiation, and the morphogenesis of tissues and organ systems that define sequential steps in the development of all animals. Importantly, it is now clear that the instructive influence of a particular ECM at various points in development reflects more than a simpl...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Dzamba BJ, DeSimone DW Tags: Curr Top Dev Biol Source Type: research

The Fish Egg's Zona Pellucida.
Abstract All fish eggs are surrounded by an envelope, called the zona pellucida (ZP), that plays various roles during oogenesis, egg deposition, fertilization, and embryogenesis. The fish egg ZP consists of only a few proteins that are homologs of mammalian ZP proteins ZP1, ZP3, and ZP4. Unlike the situation in mammals, in fishes there are often multiple copies of ZP genes, perhaps a consequence of ancient polyploidization, gene amplification, and mutation. Like mammalian ZP proteins, fish egg ZP1-like proteins exhibit conserved organization with distinct domains and motifs, but unlike mammalian ZP1 and ZP4 have a...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Litscher ES, Wassarman PM Tags: Curr Top Dev Biol Source Type: research

Egg-Coat and Zona Pellucida Proteins of Chicken as a Typical Species of Aves.
Abstract Birds are oviparous vertebrates in terrestrial animals. Birds' eggs accumulate mass of egg yolk during the egg development and are accordingly much larger than the eggs of viviparous vertebrates. Despite such difference in size and contents, the birds' eggs are surrounded with the egg-coat morphologically and compositionally resembling the mammalian egg-coat, zona pellucida. On the other hand, there are some differences in part between the two egg-coats, though relationships of such structural differences to any biological roles specific for the extracellular matrix of birds' eggs are not fully understood...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Nishio S, Okumura H, Matsuda T Tags: Curr Top Dev Biol Source Type: research

The Mouse Egg's Zona Pellucida.
Abstract All mammalian eggs are surrounded by a highly specialized extracellular matrix (ECM), called the zona pellucida (ZP), that functions before, during, and after fertilization. Unlike somatic cell ECM the mouse ZP is composed of three different proteins, ZP1-3, that are synthesized and secreted by growing oocytes and assembled into long interconnected fibrils. ECM or vitelline envelope (VE) that surrounds fish, reptilian, amphibian, and avian eggs also consists of a limited number of proteins all closely related to ZP1-3. Messenger RNAs encoding ZP1-3 are expressed only by growing oocytes at very high levels...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Wassarman PM, Litscher ES Tags: Curr Top Dev Biol Source Type: research

Conceptus Coats of Marsupials and Monotremes.
Abstract Mammals evolved from oviparous reptiles that laid eggs in a dry, terrestrial environment, thus requiring large amounts of yolk to support development and tough, outer coats to protect them. Eutherian mammals such as humans and mice exhibit an "extreme" form of viviparity in which yolk and conceptus coats have become largely redundant. However, the "other" mammals-monotremes and marsupials-have retained and modified some features of reptilian development that provide valuable insights into the evolution of viviparity in mammals. Most striking of these are the conceptus coats, which incl...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Frankenberg S, Renfree MB Tags: Curr Top Dev Biol Source Type: research

The Human Egg's Zona Pellucida.
Abstract Human zona pellucida (ZP) matrix, a delicate network of thin interconnected filaments, is primarily composed of four glycoproteins, namely, ZP1, ZP2, ZP3, and ZP4. All four zona proteins share common structural elements such as signal peptide, "ZP domain," consensus furin cleavage site, transmembrane-like domain, and short cytoplasmic tail. In addition, ZP1 and ZP4 also have "Trefoil domain." Recombinant/native human zona proteins have been used to investigate their binding characteristics to the capacitated and/or acrosome-reacted spermatozoa. These investigations revealed that ZP1, Z...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Gupta SK Tags: Curr Top Dev Biol Source Type: research

Matricellular Proteins: Functional Insights From Non-mammalian Animal Models.
Abstract The extracellular matrix (ECM) has central roles in tissue integrity and remodeling throughout the life span of animals. While collagens are the most abundant structural components of ECM in most tissues, tissue-specific molecular complexity is contributed by ECM glycoproteins. The matricellular glycoproteins are categorized primarily according to functional criteria and represented predominantly by the thrombospondin, tenascin, SPARC/osteonectin, and CCN families. These proteins do not self-assemble into ECM fibrils; nevertheless, they shape ECM properties through interactions with structural ECM protein...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Adams JC Tags: Curr Top Dev Biol Source Type: research

Structure of Zona Pellucida Module Proteins.
Abstract The egg coat, an extracellular matrix made up of glycoprotein filaments, plays a key role in animal fertilization by acting as a gatekeeper for sperm. Egg coat components polymerize using a common zona pellucida (ZP) "domain" module that consists of two related immunoglobulin-like domains, called ZP-N and ZP-C. The ZP module has also been recognized in a large number of other secreted proteins with different biological functions, whose mutations are linked to severe human diseases. During the last decade, tremendous progress has been made toward understanding the atomic architecture of the ZP mo...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Bokhove M, Jovine L Tags: Curr Top Dev Biol Source Type: research

Egg Coat Proteins Across Metazoan Evolution.
Abstract All animal oocytes are surrounded by a glycoproteinaceous egg coat, a specialized extracellular matrix that serves both structural and species-specific roles during fertilization. Egg coat glycoproteins polymerize into the extracellular matrix of the egg coat using a conserved protein-protein interaction module-the zona pellucida (ZP) domain-common to both vertebrates and invertebrates, suggesting that the basic structural features of egg coats have been conserved across hundreds of millions of years of evolution. Egg coat proteins, as with other proteins involved in reproduction, are frequently found to ...
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Killingbeck EE, Swanson WJ Tags: Curr Top Dev Biol Source Type: research

Preface.
PMID: 29853188 [PubMed - in process] (Source: Current Topics in Developmental Biology)
Source: Current Topics in Developmental Biology - June 2, 2018 Category: Biology Authors: Litscher ES, Wassarman PM Tags: Curr Top Dev Biol Source Type: research

Modeling Mammalian Gastrulation With Embryonic Stem Cells.
Abstract Understanding cell fate patterning and morphogenesis in the mammalian embryo remains a formidable challenge. Recently, in vivo models based on embryonic stem cells (ESCs) have emerged as complementary methods to quantitatively dissect the physical and molecular processes that shape the embryo. Here we review recent developments in using ESCs to create both two- and three-dimensional culture models that shed light on mammalian gastrulation. PMID: 29801527 [PubMed - in process] (Source: Current Topics in Developmental Biology)
Source: Current Topics in Developmental Biology - May 30, 2018 Category: Biology Authors: Siggia ED, Warmflash A Tags: Curr Top Dev Biol Source Type: research

The Long Road to Making Muscle In Vitro.
hal J Abstract The skeletal muscle lineage derives from the embryonic paraxial mesoderm (PM) which also gives rise to the axial skeleton, the dermis of the back, brown fat, meninges, and endothelial cells. Direct conversion was pioneered in skeletal muscle with overexpression of the transcription factor MyoD which can convert fibroblasts to a muscle fate. In contrast, directed differentiation of skeletal muscle from pluripotent cells (PC) in vitro has proven to be very difficult compared to other lineages and has only been achieved recently. Experimental strategies recapitulating myogenesis in vitro from mouse and...
Source: Current Topics in Developmental Biology - May 30, 2018 Category: Biology Authors: Pourquié O, Al Tanoury Z, Chal J Tags: Curr Top Dev Biol Source Type: research

Recapitulating and Deciphering Human Pancreas Development From Human Pluripotent Stem Cells in a Dish.
ton A Abstract Here, we review how human pluripotent stem cell models of pancreas development have emerged and became an important tool to study human development and disease. Initially developed toward the production of β cells for diabetes therapy, the protocols have been refined based on knowledge of pancreas development in model organisms. While the cells produced are closer and closer to the end goal of a functional β cell, these models have also been used to carry out functional experiments addressing gene function and expression as well as regulatory and epigenetic landscape changes during human p...
Source: Current Topics in Developmental Biology - May 30, 2018 Category: Biology Authors: Petersen MBK, Gonçalves CAC, Kim YH, Grapin-Botton A Tags: Curr Top Dev Biol Source Type: research

What Can Stem Cell Models Tell Us About Human Germ Cell Biology?
Abstract Fusion of sperm and egg generates a totipotent zygote that develops into a whole organism. Accordingly, the "immortal" germline transmits genetic and epigenetic information to subsequent generations with consequences for human health and disease. In mammals, primordial germ cells (PGCs) originate from peri-gastrulation embryos. While early human embryos are inaccessible for research, in vitro model systems using pluripotent stem cells have provided critical insights into human PGC specification, which differs from that in mice. This might stem from significant differences in early embryogenesis ...
Source: Current Topics in Developmental Biology - May 30, 2018 Category: Biology Authors: Irie N, Sybirna A, Surani MA Tags: Curr Top Dev Biol Source Type: research

From Human Pluripotent Stem Cells to Cortical Circuits.
Abstract Understanding the development of the human brain in relation with evolution is an important frontier field in developmental biology. In particular, investigating the mechanisms underlying the greatly increased relative size and complexity of the cerebral cortex, the seat of our enhanced cognitive abilities, remains a fascinating yet largely unsolved question. Though many advances in our understanding have been gained from the study of animal models, as well as human genetics and embryology, large gaps remain in our knowledge of the molecular mechanisms that control human cortical development. Interestingl...
Source: Current Topics in Developmental Biology - May 30, 2018 Category: Biology Authors: Astick M, Vanderhaeghen P Tags: Curr Top Dev Biol Source Type: research

Studying the Brain in a Dish: 3D Cell Culture Models of Human Brain Development and Disease.
Abstract The study of the cellular and molecular processes of the developing human brain has been hindered by access to suitable models of living human brain tissue. Recently developed 3D cell culture models offer the promise of studying fundamental brain processes in the context of human genetic background and species-specific developmental mechanisms. Here, we review the current state of 3D human brain organoid models and consider their potential to enable investigation of complex aspects of human brain development and the underpinning of human neurological disease. PMID: 29801532 [PubMed - in process] (Sou...
Source: Current Topics in Developmental Biology - May 30, 2018 Category: Biology Authors: Brown J, Quadrato G, Arlotta P Tags: Curr Top Dev Biol Source Type: research

Preface.
PMID: 29801533 [PubMed - in process] (Source: Current Topics in Developmental Biology)
Source: Current Topics in Developmental Biology - May 30, 2018 Category: Biology Authors: Brivanlou AH Tags: Curr Top Dev Biol Source Type: research

Introduction.
PMID: 29477159 [PubMed - in process] (Source: Current Topics in Developmental Biology)
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Plusa B, Hadjantonakis AK Tags: Curr Top Dev Biol Source Type: research

The Regulative Nature of Mammalian Embryos.
Abstract The striking developmental plasticity of early mammalian embryos has been known since the classical experiments performed in the 1950s and 1960s. There are many lines of evidence that the mammalian embryo is able to continue normal development even when exposed to severe experimental manipulations of the number and position of cells within the embryo. These observations have raised the question about the mechanisms involved in emergence, maintenance, and progressive restriction of this plasticity. Only recently, we have begun to understand these mechanisms. In this review, in order to explain the molecula...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Klimczewska K, Kasperczuk A, Suwińska A Tags: Curr Top Dev Biol Source Type: research

Cell Polarity-Dependent Regulation of Cell Allocation and the First Lineage Specification in the Preimplantation Mouse Embryo.
Abstract During the first few days in the mouse preimplantation embryo, two types of cells, polar and apolar cells are generated from spherical totipotent blastomeres. Sequential morphogenetic events, polarization, compaction, and asymmetric division, are essential for the generation of the first distinct cell populations, polar and apolar cells, which establish the outer/inner configuration within the embryo. This leads to position-dependent activation of the Hippo signaling pathway and lineage-specific gene expression to form the trophectoderm and inner cell mass in a blastocyst. It is still unknown how each mor...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Saini D, Yamanaka Y Tags: Curr Top Dev Biol Source Type: research

States and Origins of Mammalian Embryonic Pluripotency In Vivo and in a Dish.
Abstract Mouse embryonic stem cells (ESC), derived from preimplantation embryos in 1981, defined mammalian pluripotency for many decades. However, after the derivation of human ESC in 1998, comparative studies showed that different types of pluripotency exist in early embryos and that these can be captured in vitro under various culture conditions. Over the past decade much has been learned about the key signaling pathways, growth factor requirements, and transcription factor profiles of pluripotent cells in embryos, allowing improvement of derivation and culture conditions for novel pluripotent stem cell types. M...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Ramos-Ibeas P, Nichols J, Alberio R Tags: Curr Top Dev Biol Source Type: research

Capturing and Interconverting Embryonic Cell Fates in a Dish.
Abstract Cells of the early embryo are totipotent because they will differentiate to produce the fetus and its surrounding extraembryonic tissues. By contrast, embryonic stem (ES) cells are considered to be merely pluripotent because they lack the ability to efficiently produce extraembryonic cell types. The relatively limited developmental potential of ES cells can be explained by the observation that ES cells are derived from the embryo after its cells have already begun to specialize and lose totipotency. Meanwhile, at the time that pluripotent ES cell progenitors are specified, so are the multipotent progenito...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Watts J, Lokken A, Moauro A, Ralston A Tags: Curr Top Dev Biol Source Type: research

From Germline to Soma: Epigenetic Dynamics in the Mouse Preimplantation Embryo.
Abstract When reflecting about cell fate commitment we think of differentiation. Be it during embryonic development or in an adult stem cell niche, where cells of a higher potency specialize and cell fate decisions are taken. Under normal circumstances this process is definitive and irreversible. Cell fate commitment is achieved by the establishment of cell-type-specific transcriptional programmes, which in turn are guided, reinforced, and ultimately locked-in by epigenetic mechanisms. Yet, this plunging drift in cellular potency linked to epigenetically restricted access to genomic information is problematic for ...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Seah MKY, Messerschmidt DM Tags: Curr Top Dev Biol Source Type: research

Pre-gastrula Development of Non-eutherian Mammals.
Abstract Marsupials and monotremes differ from eutherian mammals in many features of their reproduction and development. Some features appear to be representative of transitional stages in evolution from therapsid reptiles to humans and mice, particularly with respect to the extraembryonic tissues that have undergone remarkable modifications to accommodate reduced egg size and quantity of yolk/deutoplasm, and increasing emphasis on viviparity and placentation. Trophoblast and hypoblast contribute the epithelial layers in most of the extraembryonic membranes and are the first two lineages to differentiate from the ...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Frankenberg S Tags: Curr Top Dev Biol Source Type: research

Pre-implantation Development of Domestic Animals.
Abstract During the first days following fertilization, cells of mammalian embryo gradually lose totipotency, acquiring distinct identity. The first three lineages specified in the mammalian embryo are pluripotent epiblast, which later gives rise to the embryo proper, and two extraembryonic lineages, hypoblast (also known as primitive endoderm) and trophectoderm, which form tissues supporting development of the fetus in utero. Most of our knowledge regarding the mechanisms of early lineage specification in mammals comes from studies in the mouse. However, the growing body of evidence points to both similarities an...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Piliszek A, Madeja ZE Tags: Curr Top Dev Biol Source Type: research

Human Pre-gastrulation Development.
Abstract Understanding the progression of early human embryonic development prior to implantation is of fundamental biological importance. Greater insights into early developmental events may lead to clinical improvements, not only via the establishment of novel stem cell models with increased potential or more physiological relevance, but also by uncovering some underlying causes of infertility, miscarriages, and developmental disorders. The majority of human embryos available for study are those donated to research once they are surplus to family building following in vitro fertilization, though in some countrie...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Wamaitha SE, Niakan KK Tags: Curr Top Dev Biol Source Type: research

The Mitochondria and the Regulation of Cell Fitness During Early Mammalian Development.
ez TA Abstract From fertilization until the onset of gastrulation the early mammalian embryo undergoes a dramatic series of changes that converts a single fertilized cell into a remarkably complex organism. Much attention has been given to the molecular changes occurring during this process, but here we will review what is known about the changes affecting the mitochondria and how they impact on the energy metabolism and apoptotic response of the embryo. We will also focus on understanding what quality control mechanisms ensure optimal mitochondrial activity in the embryo, and in this way provide an overview of th...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Lima A, Burgstaller J, Sanchez-Nieto JM, Rodríguez TA Tags: Curr Top Dev Biol Source Type: research

The Head's Tale: Anterior-Posterior Axis Formation in the Mouse Embryo.
Abstract The establishment of the anterior-posterior (A-P) axis is a fundamental event during early development and marks the start of the process by which the basic body plan is laid down. This axial information determines where gastrulation, that generates and positions cells of the three-germ layers, occurs. A-P patterning requires coordinated interactions between multiple tissues, tight spatiotemporal control of signaling pathways, and the coordination of tissue growth with morphogenetic movements. In the mouse, a specialized population of cells, the anterior visceral endoderm (AVE) undergoes a migration event...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Stower MJ, Srinivas S Tags: Curr Top Dev Biol Source Type: research

Cell Fate Decisions During Preimplantation Mammalian Development.
Abstract The early mouse embryo offers a phenomenal system to dissect how changes in the mechanisms controlling cell fate are integrated with morphogenetic events at the single-cell level. New technologies based on live imaging have enabled the discovery of dynamic changes in the regulation of single genes, transcription factors, and epigenetic mechanisms directing early cell fate decision in the early embryo. Here, we review recent progress in linking molecular dynamic events occurring at the level of the single cell in vivo, to some of the key morphogenetic changes regulating early mouse development. PMID: ...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Bissiere S, Gasnier M, Alvarez YD, Plachta N Tags: Curr Top Dev Biol Source Type: research

Our First Choice: Cellular and Genetic Underpinnings of Trophectoderm Identity and Differentiation in the Mammalian Embryo.
Abstract The trophectoderm (TE) is the first cell population to appear in the mammalian preimplantation embryo, as the result of the differentiation of totipotent blastomeres located on the outer surface of the late morula. Trophectodermal cells arrange in a monolayer covering the expanding blastocyst and acquire an epithelial phenotype with distinct apicobasal polarity and a basal lamina placed toward the blastocyst interior. During later development through the periimplantation and gastrulation stages, the TE gives rise to extraembryonic membranes and cell types that will eventually form most of the fetal placen...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Menchero S, Sainz de Aja J, Manzanares M Tags: Curr Top Dev Biol Source Type: research

Primitive Endoderm Differentiation: From Specification to Epithelialization.
Abstract At the time of implantation, the mouse blastocyst has developed three cell lineages: the epiblast (Epi), the primitive endoderm (PrE), and the trophectoderm (TE). The PrE and TE are extraembryonic tissues but their interactions with the Epi are critical to sustain embryonic growth, as well as to pattern the embryo. We review here the cellular and molecular events that lead to the production of PrE and Epi lineages and discuss the different hypotheses that are proposed for the induction of these cell types. In the second part, we report the current knowledge about the epithelialization of the PrE. PMI...
Source: Current Topics in Developmental Biology - February 28, 2018 Category: Biology Authors: Bassalert C, Valverde-Estrella L, Chazaud C Tags: Curr Top Dev Biol Source Type: research

DAF-16: FOXO in the Context of C. elegans.
Abstract In Caenorhabditis elegans, there is a single FOXO transcription factor homolog, encoded by the gene, daf-16. As a central regulator for multiple signaling pathways, DAF-16 integrates these signals which results in modulation of several biological processes including longevity, development, fat storage, stress resistance, innate immunity, and reproduction. Using C. elegans allows for studies of FOXO in the context of the whole animal. Therefore, manipulating levels or the activity of daf-16 results in phenotypic changes. Genetic and molecular analysis revealed that similar to other systems, DAF-16 is the d...
Source: Current Topics in Developmental Biology - February 14, 2018 Category: Biology Authors: Tissenbaum HA Tags: Curr Top Dev Biol Source Type: research

FOXO in Neural Cells and Diseases of the Nervous System.
Abstract The evolutionarily conserved FOXO family of transcription factors has emerged as a significant arbiter of neural cell fate and function in mammals. From the neural stem cell (NSC) state through mature neurons under both physiological and pathological conditions, they have been found to modulate neural cell survival, stress responses, lineage commitment, and neuronal signaling. Lineage-specific FOXO knockout mice have provided an invaluable tool for the dissection of FOXO biology in the nervous system. Within the NSC compartments of the brain, FOXOs are required for the maintenance of NSC quiescence and fo...
Source: Current Topics in Developmental Biology - February 14, 2018 Category: Biology Authors: Santo EE, Paik J Tags: Curr Top Dev Biol Source Type: research

Regulation of Hepatic Glucose Metabolism by FoxO Proteins, an Integrated Approach.
Abstract FoxO proteins are ancient targets of insulin action and play an important role in mediating effects of insulin on gene expression and metabolism. Regulation of FoxO function in the liver is critical for the ability of insulin to maintain glucose homeostasis and suppress hepatic glucose production (HGP), and dysregulation of FoxO function is thought to contribute to the pathogenesis of diabetes mellitus. Signaling by the insulin/PI3 kinase/Akt pathway suppresses FoxO function, and FoxO proteins also are regulated by counterregulatory factors and sirtuin deacetylases which increase their activity. FoxO prot...
Source: Current Topics in Developmental Biology - February 14, 2018 Category: Biology Authors: Unterman TG Tags: Curr Top Dev Biol Source Type: research

The Role of FoxOs in Bone Health and Disease.
Abstract Recent studies with murine models of cell-specific loss- or gain-of-function of FoxOs have provided novel insights into the function and signaling of these transcription factors on the skeleton. They have revealed that FoxO actions in chondrocytes are critical for normal skeletal development, and FoxO actions in cells of the osteoclast or osteoblast lineage greatly influence bone resorption and formation and, consequently, bone mass. FoxOs also act in osteoblast progenitors to inhibit Wnt signaling and bone formation. Additionally, FoxOs decrease bone resorption via direct antioxidant effects on osteoclas...
Source: Current Topics in Developmental Biology - February 14, 2018 Category: Biology Authors: Kim HN, Iyer S, Ring R, Almeida M Tags: Curr Top Dev Biol Source Type: research

Regulation of FOXO Factors in Mammalian Cells.
Abstract Forkhead box O (FOXO) transcription factors are central regulators of cellular homeostasis. FOXOs respond to a wide range of external stimuli, including growth factor signaling, oxidative stress, genotoxic stress, and nutrient deprivation. These signaling inputs regulate FOXOs through a number of posttranslational modifications, including phosphorylation, acetylation, ubiquitination, and methylation. Covalent modifications can affect localization, DNA binding, and interactions with other cofactors in the cell. FOXOs integrate the various modifications to regulate cell type-specific gene expression program...
Source: Current Topics in Developmental Biology - February 14, 2018 Category: Biology Authors: Brown AK, Webb AE Tags: Curr Top Dev Biol Source Type: research

FOXO3 and Exceptional Longevity: Insights From Hydra to Humans.
Abstract Aging is a complex, multifactorial process with significant plasticity. While several biological pathways appear to influence aging, few genes have been identified that are both evolutionarily conserved and have a strong impact on aging and age-related phenotypes. The FoxO3 gene (FOXO3), and its homologs in model organisms, appears especially important, forming a key gene in the insulin/insulin-like growth factor-signaling pathway, and influencing life span across diverse species. We highlight some of the key findings that are associated with FoxO3 protein, its gene and homologs in relation to lifespan in...
Source: Current Topics in Developmental Biology - February 14, 2018 Category: Biology Authors: Davy PMC, Allsopp RC, Donlon TA, Morris BJ, Willcox DC, Willcox BJ Tags: Curr Top Dev Biol Source Type: research

Stem Cells Seen Through the FOXO Lens: An Evolving Paradigm.
Abstract Stem cells self-renew and differentiate to generate all tissues and cells in the body. Stem cell health promotes adaptive responses to tissue damage or loss and is essential for tissue regeneration with age. In the past decade, the evolutionarily conserved transcription factors FOXO with known functions in promoting healthy aging have emerged as key regulators of stem cell homeostasis in various tissues, including blood, neural, and muscle stem cells. Aberrant FOXO functions have been implicated in a variety of disorders including neurodegenerative, blood, cancer, and diabetes some of which are fostered b...
Source: Current Topics in Developmental Biology - February 14, 2018 Category: Biology Authors: Liang R, Ghaffari S Tags: Curr Top Dev Biol Source Type: research

FOXOs Maintaining the Equilibrium for Better or for Worse.
Abstract A paradigm shift is emerging within the FOXO field and accumulating evidence indicates that we need to reappreciate the role of FOXOs, at least in cancer development. Here, we discuss the possibility that FOXOs are both tumor suppressors as well as promoters of tumor progression. This is mostly dependent on the biological context. Critical to this dichotomous role is the notion that FOXOs are central in preserving cellular homeostasis in redox control, genomic stability, and protein turnover. From this perspective, a paradoxical role in both suppressing and enhancing tumor progression can be reconciled. A...
Source: Current Topics in Developmental Biology - February 14, 2018 Category: Biology Authors: van Doeselaar S, Burgering BMT Tags: Curr Top Dev Biol Source Type: research

Preface.
PMID: 29433741 [PubMed - in process] (Source: Current Topics in Developmental Biology)
Source: Current Topics in Developmental Biology - February 14, 2018 Category: Biology Authors: Ghaffari S Tags: Curr Top Dev Biol Source Type: research

"What Did Maxwell's Equations Really Have to Do With Edison's Invention?": Addressing the Complexity of Developing Clinical Interventions for Skeletal Muscle Disease.
"What Did Maxwell's Equations Really Have to Do With Edison's Invention?": Addressing the Complexity of Developing Clinical Interventions for Skeletal Muscle Disease. Curr Top Dev Biol. 2018;126:1-22 Authors: Dando J Abstract To reach the healthcare market and have a medical intervention reimbursed in any format carries high risk and very low success rates. Even when all regulatory hurdles have been surpassed, there is no guarantee that the product will be purchased; a different body makes that decision using criteria typically unknown to early-stage innovators and intervention developers. I...
Source: Current Topics in Developmental Biology - January 7, 2018 Category: Biology Authors: Dando J Tags: Curr Top Dev Biol Source Type: research

Cellular Biomechanics in Skeletal Muscle Regeneration.
Abstract Satellite cells, adult stem cells in skeletal muscle tissue, reside within a mechanically dynamic three-dimensional microenvironment. With each contraction-relaxation cycle, a satellite cell is expected to experience tensile, shear, and compressive stresses, and through cell-extracellular matrix interactions, also gauge the stiffness of the niche. Via mechanoreceptors, cells can sense these biophysical parameters of the niche, which serve to physically induce conformational changes that impact biomolecule activity, and thereby alter downstream signal transduction pathways and ultimately cell fate. An emer...
Source: Current Topics in Developmental Biology - January 7, 2018 Category: Biology Authors: Li EW, McKee-Muir OC, Gilbert PM Tags: Curr Top Dev Biol Source Type: research

Satellite Cell Self-Renewal.
Abstract Adult skeletal muscle is endowed with regenerative potential through partially recapitulating the embryonic developmental program. Upon acute injury or in pathological conditions, quiescent muscle-resident stem cells, called satellite cells, become activated and give rise to myogenic progenitors that massively proliferate, differentiate, and fuse to form new myofibers and restore tissue functionality. In addition, a proportion of activated cells returns back to quiescence and replenish the pool of satellite cells in order to maintain the ability of skeletal muscle tissue to repair. Self-renewal is the pro...
Source: Current Topics in Developmental Biology - January 7, 2018 Category: Biology Authors: Giordani L, Parisi A, Le Grand F Tags: Curr Top Dev Biol Source Type: research

"Known Unknowns": Current Questions in Muscle Satellite Cell Biology.
"Known Unknowns": Current Questions in Muscle Satellite Cell Biology. Curr Top Dev Biol. 2018;126:205-233 Authors: Cornelison D Abstract Our understanding of satellite cells, now known to be the obligate stem cells of skeletal muscle, has increased dramatically in recent years due to the introduction of new molecular, genetic, and technical resources. In addition to their role in acute repair of damaged muscle, satellite cells are of interest in the fields of aging, exercise, neuromuscular disease, and stem cell therapy, and all of these applications have driven a dramatic increase in our un...
Source: Current Topics in Developmental Biology - January 7, 2018 Category: Biology Authors: Cornelison D Tags: Curr Top Dev Biol Source Type: research

The Muscle Stem Cell Niche in Health and Disease.
Abstract The regulation of stem cells that maintain and regenerate postnatal tissues depends on extrinsic signals originating from their microenvironment, commonly referred to as the stem cell niche. Complex higher-order regulatory interrelationships with the tissue and factors in the systemic circulation are integrated and propagated to the stem cells through the niche. The stem cell niche in skeletal muscle tissue is both a paradigm for a structurally and functionally relatively static niche that maintains stem cell quiescence during tissue homeostasis, and a highly dynamic regenerative niche that is subject to ...
Source: Current Topics in Developmental Biology - January 7, 2018 Category: Biology Authors: Mashinchian O, Pisconti A, Le Moal E, Bentzinger CF Tags: Curr Top Dev Biol Source Type: research