Interactions between the Foot and the Head Patterning Systems in Hydra vulgaris

The Cnidarian, hydra, is an appealing model system for studying the basic processes underlying pattern formation. Classical studies have elucidated much basic information regarding the role of development gradients, and theoretical models have been quite successful at describing experimental results. However, most experiments and computer simulations have dealt with isolated patterning events such as the dynamics of head regeneration. More global events such as interactions among the head, bud, and foot patterning systems have not been extensively addressed. The characterization of monoclonal antibodies with position-specific labeling patterns and the recent cloning and characterization of genes expressed in position-specific manners now provide the tools for investigating global interactions between patterning systems. In particular, changes in the axial positional value gradient may be monitored in response to experimental perturbation. Rather than studying isolated patterning events, this approach allows us to study patterning over the entire animal. The studies reported here focus on interactions between the foot and the head patterning systems in Hydra vulgaris following induction of a foot in close proximity to a head, axial grafting of a foot closer to the head, or doubling the amount of basal tissue by lateral grafting of an additional peduncle-foot onto host animals. Resulting positional value changes as monitored by antigen (TS19) and gene (ks1 and CnNK-2) expression were assessed in the foot, head, and intervening tissue. The results of the experiments indicate that positional values changed rapidly, in a matter of hours, and that there were reciprocal interactions between the foot and the head patterning systems. Theoretical interpretations of the results in the form of computer simulations based on the reaction-diffusion model are presented and predict many, but not all, of the experimental observations. Since the lateral grafting experiment cannot, at present, be simulated, it is discussed in light of what has been learned from the axial grafting experiments and their simulations.     

Self‐organized developmental patterning and differentiation in cerebral organoids

Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self‐organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso‐ventral identities can be generated within continuous neuroepithelia. Consistent with this, we demonstrate the presence of forebrain organizing centers that express secreted growth factors, which may be involved in dorso‐ventral patterning within organoids. Furthermore, we demonstrate the timed generation of neurons with mature morphologies, as well as the subsequent generation of astrocytes and oligodendrocytes. Our work provides the methodology and quality criteria for phenotypic analysis of brain organoids and shows that the spatial and temporal patterning events governing human brain development can be recapitulated in vitro.     

Root architecture: Influence of metameric organization and emission of lateral roots

Abstract

It has yet to be established whether or not root architecture results from a metameric organization similar to that recognizable in the stem. To address this question, we have reviewed the data on the major cytological, histological and anatomical events underlying root development and on the intrinsic factors controlling these events. The evidence emerging from this review indicates that root architecture has a metameric organization that can be ‘deranged’ when environmental factors interfere with the intrinsic factors rhythmically controlling lateral root development. Metameric patterning occurs in the primary body of a root, but not in the secondary body. This difference can be attributed to the fact that primary and secondary body roots arise from completely different tissues. The root system of a woody plant is very complex, and its architecture is largely governed by roots with a secondary body organization that lack metameric patterning. The architectural contribution of the portion of roots with a primary body organization, where metameric patterning could be present, is negligible. This explains why it is difficult to recognize metameric patterning in the root architecture of these plants.     

Nemo is an inducible antagonist of Wingless signaling during Drosophila wing development

The cellular events that govern patterning during animal development must be precisely regulated. This is achieved by extrinsic factors and through the action of both positive and negative feedback loops. Wnt/Wg signals are crucial across species in many developmental patterning events. We report that Drosophila nemo (nmo) acts as an intracellular feedback inhibitor of Wingless (Wg) and that it is a novel Wg target gene. Nemo antagonizes the activity of the Wg signal, as evidenced by the finding that reduction of nmo rescues the phenotypic defects induced by misexpression of various Wg pathway components. In addition, the activation of Wg-dependent gene expression is suppressed in wing discs ectopically expressing nmo and enhanced cell autonomously in nmo mutant clones. We find that nmo itself is a target of Wg signaling in the imaginal wing disc. nmo expression is induced upon high levels of Wg signaling and can be inhibited by interfering with Wg signaling. Finally, we observe alterations in Arm stabilization upon modulation of Nemo. These observations suggest that the patterning mechanism governed by Wg involves a negative feedback circuit in which Wg induces expression of its own antagonist Nemo.     

Sonic hedgehog is required for cardiac outflow tract and neural crest cell development

The Hedgehog signaling pathway is critical for a significant number of developmental patterning events. In this study, we focus on the defects in pharyngeal arch and cardiovascular patterning present in Sonic hedgehog (Shh) null mouse embryos. Our data indicate that, in the absence of Shh, there is general failure of the pharyngeal arch development leading to cardiac and craniofacial defects. The cardiac phenotype results from arch artery and outflow tract patterning defects, as well as abnormal development of migratory neural crest cells (NCCs). The constellation of cardiovascular defects resembles a severe form of the human birth defect syndrome tetralogy of Fallot with complete pulmonary artery atresia. Previous studies have demonstrated a role for Shh in NCC survival and proliferation at later stages of development. Our data suggest that SHH signaling does not act directly on NCCs as a survival factor, but rather acts to restrict the domains that NCCs can populate during early stages (e8.5-10.5) of cardiovascular and craniofacial development.     

Isolation and Community: A Review of the Role of Gap-Junctional Communication in Embryonic Patterning

Gap junctions are specialized channels formed between the membranes of two adjacent cells. They permit the direct passage of small molecules from the cytosol of one cell to that of its neighbor, and thus form a system of cell-cell communication that exists alongside familiar secretion/receptor signaling. Gap junction states can be regulated at many levels by factors such as membrane voltage, pH, phosphorylation state, and biochemical signals. Because of the rich potential for regulation of junctional conductance, and directional and molecular gating (specificity), gap junctional communication (GJC) plays a crucial role in many aspects of normal tissue physiology, as well as in tumor progression. However, arguably the most exciting role for GJC is in the regulation of information flow that takes place during embryonic development. This review summarizes the current knowledge of how GJC controls various aspects of embryonic morphogenesis in both vertebrate and invertebrate systems. Modern molecular embryology approaches have complemented biophysical and ultrastructural data, and we are beginning to unravel the patterning roles of GJC in embryonic events such as the patterning of the embryonic left-right axis, as well as the morphogenesis of the heart and limb. Proteins from the Connexin (Cx) gene family, as well as innexins and ductin, are now beginning to be understood as the basis for GJC underlying important embryonic patterning events.     

Wnt/beta-catenin signaling and body plan formation in mouse embryos

Wnt/beta-catenin signaling plays fundamental roles in body patterning in many invertebrate and vertebrate species, by acting as a key regulator of germ layer and body axis specification. This article focuses on the roles of Wnt/beta-catenin signaling in mouse early embryos, which exhibit a unique mode of development compared to non-mammalian vertebrates. Current experimental evidence suggests that Wnt/beta-catenin signaling is not essential for patterning embryos before implantation. However, Wnt/beta-catenin signaling regulates critical developmental events after implantation, namely the patterning of visceral endoderm, the induction of primitive streak, and the formation of anterior neural ectoderm. While Wnt/beta-catenin signaling regulates the body axis formation in both mouse and frog, the mode of its action is significantly diverged between these two vertebrate species.     

SEUSS and AINTEGUMENTA mediate patterning and ovule initiation during gynoecium medial domain development

The Arabidopsis (Arabidopsis thaliana) gynoecium, the female floral reproductive structure, requires the action of genes that specify positional identities during its development to generate an organ competent for seed development and dispersal. Early in gynoecial development, patterning events divide the primordium into distinct domains that will give rise to specific tissues and organs. The medial domain of the gynoecium gives rise to the ovules, and several other structures critical for reproductive competence. Here we report a synergistic genetic interaction between seuss and aintegumenta mutants resulting in a complete loss of ovule initiation and a reduction of the structures derived from the medial domain. We show that patterning events are disrupted early in the development of the seuss aintegumenta gynoecia and we identify PHABULOSA (PHB), REVOLUTA, and CRABS CLAW (CRC) as potential downstream targets of SEUSS (SEU) and AINTEGUMENTA (ANT) regulation. Our genetic data suggest that SEU additionally functions in pathways that are partially redundant and parallel to PHB, CRC, and ANT. Thus, SEU and ANT are part of a complex and robust molecular system that coordinates patterning cues and cellular proliferation along the three positional axes of the developing gynoecium.     

Dorsoventral differences in cAMP levels and correlated changes in the subcellular distribution of the PKA catalytic domain,provide further evidence that PKA signaling coordinates dorsoventral patterning of the otocyst

Dorsoventral (DV) patterning of the otocyst gives rise to formation of the morphologically and functionally complex membranous labyrinth composed of unique dorsal and ventral sensory organs. DV patterning results from extracellular signaling by secreted growth factors, which presumably form reciprocal concentration gradients across the DV axis of the otocyst. Previous work suggested a model in which two important growth factors, bone morphogenetic protein (BMP) and SHH, undergo crosstalk through an intersecting pathway to coordinate DV patterning. cAMP‐dependent protein kinase A (PKA) lies at the heart of this pathway. Here, we provide further evidence that PKA signaling coordinates DV patterning, showing that both BMPs and SHH regulate cAMP levels, with BMPs increasing levels in the dorsal otocyst and SHH decreasing levels in the ventral otocyst. This, in turn, results in regional changes in the subcellular distribution of the catalytic domain of PKA, as well as DV regulation of PKA activity, increasing it dorsally and decreasing it ventrally. These new results fill an important gap in our previous understanding of how ligand signaling acts intracellularly during otocyst DV patterning and early morphogenesis, thereby initiating the series of events leading to formation of the inner ear sensory organs that function in balance and hearing.     

Cell communities and robustness in development

The robustness of patterning events in development is a key feature that must be accounted for in proposed models of these events. When considering explicitly cellular systems, robustness can be exhibited at different levels of organization. Consideration of two widespread patterning mechanisms suggests that robustness at the level of cell communities can result from variable development at the level of individual cells; models of these mechanisms show how interactions between participating cells guarantee community-level robustness. Cooperative interactions enhance homogeneity within communities of like cells and the sharpness of boundaries between communities of distinct cells, while competitive interactions amplify small inhomogeneities within communities of initially equivalent cells, resulting in fine-grained patterns of cell specialization.     

Morphogenesis and dysmorphogenesis of the appendicular skeleton

Cartilage patterning and differentiation are prerequisites for skeletal development through endochondral ossification (EO). Multipotential mesenchymal cells undergo a complex process of cell fate determination to become chondroprogenitors and eventually differentiate into chondrocytes. These developmental processes require the orchestration of cell-cell and cell-matrix interactions. In this review, we present limb bud development as a model for cartilage patterning and differentiation. We summarize the molecular and cellular events and signaling pathways for axis patterning, cell condensation, cell fate determination, digit formation, interdigital apoptosis, EO, and joint formation. The interconnected nature of these pathways underscores the effects of genetic and teratogenic perturbations that result in skeletal birth defects. The topics reviewed also include limb dysmorphogenesis as a result of genetic disorders and environmental factors, including FGFR, GLI3, GDF5/CDMP1, Sox9, and Cbfa1 mutations, as well as thalidomide- and alcohol-induced malformations. Understanding the complex interactions involved in cartilage development and EO provides insight into mechanisms underlying the biology of normal cartilage, congenital disorders, and pathologic adult cartilage.     

Cellular patterning of the vertebrate embryo

Recent studies show that cell dispersal is a widespread phenomenon in the development of early vertebrate embryos. These cell movements coincide with major decisions for the spatial organization of the embryo, and they parallel genetic patterning events. For example, in the central nervous system, cell dispersal is first mainly anterior–posterior and subsequently dorsal–ventral. Thus, genes expressed in signaling centers of the embryo probably control cell movements, tightly linking cellular and genetic patterning. Cell dispersal might be important for the correct positioning of cells and tissues involved in intercellular signaling. The emergence of cell dispersal at the onset of vertebrate evolution indicates a shift from early, lineage-based cellular patterning in small embryos to late, movement-based cellular patterning of polyclones in large embryos. The conservation of the same basic body plan by invertebrate and vertebrate chordates suggests that evolution of the embryonic period preceding the phylotypic stage was by intercalary co-option of basic cell activities present in the ancestral metazoan cell.     

The dominant mutant Wavy auricle in blade1 disrupts patterning in a lateral domain of the maize leaf

Mature maize leaves have defined cell types along the proximal distal and medial lateral axes. The patterning events that establish these axes take place early in leaf initiation. We have identified a new dominant mutation, Wavy auricle in blade1 (Wab1), which affects patterning in both axes in a dose-dependent manner. Wab1 leaves are narrower than normal leaves and displace proximal tissues distally. We show that the proximal distal patterning defects are not due to misexpression of knox genes. Genetic analyses suggest that the action of dominant Wab1 alleles is localized to a lateral domain of the leaf, located between the midvein and the marginal domain that is determined by narrow sheath function. Thus, Wab1 defines a knox-independent pathway that affects specification of the proximal distal axis of the maize leaf. We suggest that failure to elaborate a normal lateral domain in the Wab1 leaf is responsible for disrupting patterning of the proximal distal axis.     

Antero-posterior patterning of the vertebrate digestive tract: 40 years after Nicole Le Douarin's PhD thesis

This review is dedicated to the work on chick digestive tract organogenesis that Nicole Le Douarin performed as a PhD student under the direction of Etienne Wolf. I discuss how she laid the grounds for future work by establishing fate maps at somitic stages, by describing morphogenetic movements between germ layers and by pointing to signaling events between endoderm and mesoderm. Her inspiring work was extended by others, in particular at the molecular level, leading to a better understanding of antero-posterior patterning in the digestive tract. Antero-posterior patterning of endoderm is initiated at gastrulation when future anterior and posterior endoderm ingress at different times and accordingly express different genes. Plasticity is however maintained at somite stages and even later, when organ primordia can be delineated. There is a cross-talk between endoderm and mesoderm and the two layers exchange instructive signals that induce specific antero-posterior identities as well as permissive signals required for organogenesis from previously patterned fields. Recent experiments suggest that several signaling molecules involved in neural tube antero-posterior patterning are also instrumental in the digestive tract including retinoic acid and FGF4.