Annual Review of Cell and Developmental Biology - Volume 28, 2012

Laminins are a large family of conserved, multidomain trimeric basement membrane proteins that contribute to the structure of extracellular matrix and influence the behavior of associated cells, such as adhesion, differentiation, migration, phenotype stability, and resistance to anoikis. In lower organisms such as Hydra there is only one isoform of laminin, but higher organisms have at least 16 trimeric isoforms with varying degrees of cell/tissue specificity. In vitro protein and cell culture studies, gene manipulation in animals, and laminin gene mutations in human diseases have provided insight into the specific functions of some laminins, but the biological roles of many isoforms are still largely unexplored, mainly owing to difficulties in isolating them in pure form from tissues or cells. In this review, we elucidate the evolution of laminins, describe their molecular complexity, and explore the current knowledge of their diversity and functional aspects, including laminin-mediated signaling via membrane receptors, in vitro cell biology, and involvement in various tissues gained from animal model and human disease studies. The potential use of laminins in cell biology research and biotechnology is discussed.

Long interspersed element-1 (LINE-1 or L1) is a repetitive DNA retrotransposon capable of duplication by a copy-and-paste genetic mechanism. Scattered throughout mammalian genomes, L1 is typically quiescent in most somatic cell types. In developing neurons, however, L1 can express and retrotranspose at high frequency. The L1 element can insert into various genomic locations including intragenic regions. These insertions can alter the dynamic of the neuronal transcriptome by changing the expression pattern of several nearby genes. The consequences of L1 genomic alterations in somatic cells are still under investigation, but the high level of mutagenesis within neurons suggests that each neuron is genetically unique. Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects. In this review, we survey the literature related to neurodevelopmental retrotransposition and discuss possible relevance to neuronal function, evolution, and neurological disease.

Axon degeneration is the pivotal pathological event of acute traumatic neural injury as well as many chronic neurodegenerative diseases. It is an active cellular program and yet molecularly distinct from cell death. Much effort is devoted toward understanding the nature of axon degeneration and promoting axon regeneration. However, the fundamental mechanisms of self-destruction of damaged axons remain unclear, and there are still few treatments for traumatic brain injury (TBI) or spinal cord injury (SCI). Genetically approachable model organisms such as Drosophila melanogaster, the fruit fly, have proven exceptionally successful in modeling human neurodegenerative diseases. More recently, this success has been extended into the field of acute axon injury and regeneration. In this review, we discuss recent findings, focusing on how these models hold promise for accelerating mechanistic insight into axon injury and identifying potential therapeutic targets for TBI and SCI.

Cell polarization is an evolutionarily conserved process that facilitates asymmetric distribution of organelles and proteins and that is modified dynamically during physiological processes such as cell division, migration, and morphogenesis. The plasticity with which cells change their behavior and phenotype in response to cell intrinsic and extrinsic cues is an essential feature of normal physiology. In disease states such as cancer, cells lose their ability to behave normally in response to physiological cues. A molecular understanding of mechanisms that alter the behavior of cancer cells is limited. Cell polarity proteins are a recognized class of molecules that can receive and interpret both intrinsic and extrinsic signals to modulate cell behavior. In this review, we discuss how cell polarity proteins regulate a diverse array of biological processes and how they can contribute to alterations in the behavior of cancer cells.

Planar cell polarity (PCP), the orientation and alignment of cells within a sheet, is a ubiquitous cellular property that is commonly governed by the conserved set of proteins encoded by so-called PCP genes. The PCP proteins coordinate developmental signaling cues with individual cell behaviors in a wildly diverse array of tissues. Consequently, disruptions of PCP protein functions are linked to defects in axis elongation, inner ear patterning, neural tube closure, directed ciliary beating, and left/right patterning, to name only a few. This review attempts to synthesize what is known about PCP and the PCP proteins in vertebrate animals, with a particular focus on the mechanisms by which individual cells respond to PCP cues in order to execute specific cellular behaviors.

Epithelial tissue formation and function requires the apical-basal polarization of individual epithelial cells. Apical polarity regulators (APRs) are an evolutionarily conserved group of key factors that govern polarity and several other aspects of epithelial differentiation. APRs compose a diverse set of molecules including a transmembrane protein (Crumbs), a serine/threonine kinase (aPKC), a lipid phosphatase (PTEN), a small GTPase (Cdc42), FERM domain proteins (Moesin, Yurt), and several adaptor or scaffolding proteins (Bazooka/Par3, Par6, Stardust, Patj). These proteins form a dynamic cooperative network that is engaged in negative-feedback regulation with basolateral polarity factors to set up the epithelial apical-basal axis. APRs support the formation of the apical junctional complex and the segregation of the junctional domain from the apical membrane. It is becoming increasingly clear that APRs interact with the cytoskeleton and vesicle trafficking machinery, regulate morphogenesis, and modulate epithelial cell growth and survival. Not surprisingly, APRs have multiple fundamental links to human diseases such as cancer and blindness.

Gastrulation is a fundamental phase of animal embryogenesis during which germ layers are specified, rearranged, and shaped into a body plan with organ rudiments. Gastrulation involves four evolutionarily conserved morphogenetic movements, each of which results in a specific morphologic transformation. During emboly, mesodermal and endodermal cells become internalized beneath the ectoderm. Epibolic movements spread and thin germ layers. Convergence movements narrow germ layers dorsoventrally, while concurrent extension movements elongate them anteroposteriorly. Each gastrulation movement can be achieved by single or multiple motile cell behaviors, including cell shape changes, directed migration, planar and radial intercalations, and cell divisions. Recent studies delineate cyclical and ratchet-like behaviors of the actomyosin cytoskeleton as a common mechanism underlying various gastrulation cell behaviors. Gastrulation movements are guided by differential cell adhesion, chemotaxis, chemokinesis, and planar polarity. Coordination of gastrulation movements with embryonic polarity involves regulation by anteroposterior and dorsoventral patterning systems of planar polarity signaling, expression of chemokines, and cell adhesion molecules.

The heart holds the monumental yet monotonous task of maintaining circulation. Although cardiac function is critical to other organs and to life itself, mammals are not equipped with significant natural capacity to replace heart muscle that has been lost by injury. This deficiency plays a role in leaving millions worldwide vulnerable to heart failure each year. By contrast, certain other vertebrate species such as zebrafish are strikingly good at heart regeneration. A cellular and molecular understanding of endogenous regenerative mechanisms and advances in methodology to transplant cells together project a future in which cardiac muscle regeneration can be therapeutically stimulated in injured human hearts. This review focuses on what has been discovered recently about cardiac regenerative capacity and how natural mechanisms of heart regeneration in model systems are stimulated and maintained.

One of the chief aims of modern biology is to understand the causes and mechanisms of morphological evolution. Multicellular animals display a stunning diversity of shapes and sizes of their bodies and individual suborganismal structures, much of it important to their survival. What is the most efficient way to study the evolution of morphological diversity? The old-new field of evolutionary developmental biology (evo-devo) can be particularly useful for understanding the origins of animal forms, as it aims to consolidate advances from disparate fields such as phylogenetics, genomics, morphometrics, cell biology, and developmental biology. We analyze the structure of some of the most successful recent evo-devo studies, which we see as having three distinct but highly interdependent components: (a) morphometrics, (b) identification of candidate mechanisms, and (c) functional experiments. Our case studies illustrate how multifarious evo-devo approaches taken within the three-winged evo-devo research program explain developmental mechanisms for morphological evolution across different phylogenetic scales.