Parallels between cerebellum- and amygdala-dependent conditioning

Recent evidence from cerebellum-dependent motor learning and amygdala-dependent fear conditioning indicates that, despite being mediated by different brain systems, these forms of learning might use a similar sequence of events to form new memories. In each case, learning seems to induce changes in two different groups of neurons. Changes in the first class of cells are induced very rapidly during the initial stages of learning, whereas changes in the second class of cells develop more slowly and are resistant to extinction. So, anatomically distinct cell populations might contribute differentially to the initial encoding and the long-term storage of memory in these two systems.     

Cell adhesion in embryo morphogenesis

Visualizing and analyzing shape changes at various scales, ranging from single molecules to whole organisms, are essential for understanding complex morphogenetic processes, such as early embryonic development. Embryo morphogenesis relies on the interplay between different tissues, the properties of which are again determined by the interaction between their constituent cells. Cell interactions, on the other hand, are controlled by various molecules, such as signaling and adhesion molecules, which in order to exert their functions need to be spatiotemporally organized within and between the interacting cells. In this review, we will focus on the role of cell adhesion functioning at different scales to organize cell, tissue and embryo morphogenesis. We will specifically ask how the subcellular distribution of adhesion molecules controls the formation of cell-cell contacts, how cell-cell contacts determine tissue shape, and how tissue interactions regulate embryo morphogenesis.     

Transitions between epithelial and mesenchymal states and the morphogenesis of the early mouse embryo

Multicellular organisms arise from the generation of different cell types and the organization of cells into tissues and organs. Cells of metazoa display two main phenotypes, the ancestral epithelial state and the recent mesenchymal derivative. Epithelial cells are usually stationary and reside in twodimensional sheets. By contrast mesenchymal cells are loosely packed and can move to new positions, thereby providing a vehicle for cell rearrangement, dispersal and novel cell-cell interactions. Transitions between epithelial and mesenchymal states drive key morphogenetic events in the early vertebrate embryo, including gastrulation, germ layer formation and somitogenesis. The cell behaviors and molecular mechanisms promoting transitions between these two states in the early mouse embryo are discussed in this review.Key words: mouse embryo, EMT, MET, morphogenesis, gastrulation, somitogenesis, epiblast, mesoderm, endoderm, primitive streak, paraxial mesoderm     

Transitions between epithelial and mesenchymal states and the morphogenesis of the early mouse embryo

Multicellular organisms arise from the generation of different cell types and the organization of cells into tissues and organs. Cells of metazoa display two main phenotypes, the ancestral epithelial state and the recent mesenchymal derivative. Epithelial cells are usually stationary and reside in two-dimensional sheets. By contrast mesenchymal cells are loosely packed and can move to new positions, thereby providing a vehicle for cell rearrangement, dispersal and novel cell-cell interactions. Transitions between epithelial and mesenchymal states drive key morphogenetic events in the early vertebrate embryo, including gastrulation, germ layer formation and somitogenesis. The cell behaviors and molecular mechanisms promoting transitions between these two states in the early mouse embryo are discussed in this review.     

Vascular morphogenesis in the zebrafish embryo

During embryonic development, the vertebrate vasculature is undergoing vast growth and remodeling. Blood vessels can be formed by a wide spectrum of different morphogenetic mechanisms, such as budding, cord hollowing, cell hollowing, cell wrapping and intussusception. Here, we describe the vascular morphogenesis that occurs in the early zebrafish embryo. We discuss the diversity of morphogenetic mechanisms that contribute to vessel assembly, angiogenic sprouting and tube formation in different blood vessels and how some of these complex cell behaviors are regulated by molecular pathways.     

Planar polarity and tissue morphogenesis

Planar polarity is a global, tissue-level phenomenon that coordinates cell behavior in a two-dimensional plane. The Frizzled/planar cell polarity (PCP) and anterior-posterior (AP) patterning systems for planar polarity operate in a variety of cell types and provide direction to cells with different morphologies and behaviors. These two systems involve different sets of proteins but both use directional cues provided locally by communication between neighboring cells. This review describes our current understanding of the mechanisms that transmit directional signals from cell to cell and compares the strategies for generating global systems of spatial information in stationary and dynamic cell populations.     

The embryo makes red blood cell progenitors in every tissue simultaneously with blood vessel morphogenesis

During embryonic life, hematopoiesis occurs first in the yolk sac, followed by the aorto-gonado-mesonephric region, the fetal liver, and the bone marrow. The possibility of hematopoiesis in other embryonic sites has been suspected for a long time. With the use of different methodologies (transgenic mice, electron microscopy, laser capture microdissection, organ culture, and cross-transplant experiments), we show that multiple regions within the embryo are capable of forming blood before and during organogenesis. This widespread phenomenon occurs by hemo-vasculogenesis, the formation of blood vessels accompanied by the simultaneous generation of red blood cells. Erythroblasts develop within aggregates of endothelial cell precursors. When the lumen forms, the erythroblasts "bud" from endothelial cells into the forming vessel. The extensive hematopoietic capacity found in the embryo helps explain why, under pathological circumstances such as severe anemia, extramedullary hematopoiesis can occur in any adult tissue. Understanding the intrinsic ability of tissues to manufacture their own blood cells and vessels has the potential to advance the fields of organogenesis, regeneration, and tissue engineering.     

Parallels and contrasts between iron and copper metabolism

This paper reviews the Second International Workshop on Iron and Copper Homeostasis, held in Pucón, Chile 10–13 November, 2001. We cover the presentations and papers published (this issue) with the intent to point out parallels, contrasts and cutting edge areas rather than to say something about every paper. Iron and copper metabolism have been intertwined for nearly 150 years and the interrelationship is growing with advances in understanding the role of ceruloplasmin as one example and the probable role of hephaestin as another. The transporter DMT1 (divalent metal transporter 1) clearly plays a major part in iron uptake and trafficking. Emerging evidence suggests that it plays a lesser role in manganese, cadmium and copper transport; but it is still being evaluated there. Yet another interaction may come from the IRE/IRP (Iron Responsive Element/Iron Regulatory Protein) story where a paradigmatic role in iron homeostasis is well established, but interaction with copper is only now emerging. Parallels include the nutrient status of both metals based on their utility for redox reactions as well as their toxicity primarily via reactive oxygen species. The workshop also revealed that alternate splicing of pre-mRNAs for iron and copper related proteins and tissue specific responses are additional similarities. Regulation of gene expression and excretion offered contrasts between the two metals. The workshop also considered a series of continuing and emerging issues.     

Determination and morphogenesis in the sea urchin embryo

The study of the sea urchin embryo has contributed importantly to our ideas about embryogenesis. This essay re-examines some issues where the concerns of classical experimental embryology and cell and molecular biology converge. The sea urchin egg has an inherent animal-vegetal polarity. An egg fragment that contains both animal and vegetal material will produce a fairly normal larva. However, it is not clear to what extent the oral-aboral axis is specified in embryos developing from meridional fragments. Newly available markers of the oral-aboral axis allow this issue to be settled. When equatorial halves, in which animal and vegetal hemispheres are separated, are allowed to develop, the animal half forms a ciliated hollow ball. The vegetal half, however, often forms a complete embryo. This result is not in accord with the double gradient model of animal and vegetal characteristics that has been used to interpret almost all defect, isolation and transplantation experiments using sea urchin embryos. The effects of agents used to animalize and vegetalize embryos are also due for re-examination. The classical animalizing agent, Zn2+, causes developmental arrest, not expression of animal characters. On the other hand, Li+, a vegetalizing agent, probably changes the determination of animal cells. The stability of these early determinative steps may be examined in dissociation-reaggregation experiments, but this technique has not been exploited extensively. The morphogenetic movements of primary mesenchyme are complex and involve a number of interactions. It is curious that primary mesenchyme is dispensable in skeleton formation since in embryos devoid of primary mesenchyme, the secondary mesenchyme cells will form skeletal elements. It is likely that during its differentiation the primary mesenchyme provides some of its own extracellular microenvironment in the form of collagen and proteoglycans. The detailed form of spicules made by primary mesenchyme is determined by cooperation between the epithelial body wall, the extracellular material and the inherent properties of primary mesenchyme cells. Gastrulation in sea urchins is a two-step process. The first invagination is a buckling, the mechanism of which is not understood. The secondary phase in which the archenteron elongates across the blastocoel is probably driven primarily by active cell repacking. The extracellular matrix is important for this repacking to occur, but the basis of the cellular-environmental interaction is not understood.(ABSTRACT TRUNCATED AT 400 WORDS)     

Extracellular matrix signaling in morphogenesis and repair

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Either chick embryo dermis or retinoid-treated mouse dermis can initiate glandular morphogenesis from mammalian epidermal tissue

Excess retinoids can cause developing mouse vibrissa follicles to be transformed into mucous glands in organ culture. The objective was to test the hypothesis that retinoids act in this system by altering morphogenetic properties of the dermis. After inititation by retinoic acid (RA) in organ culture, glands were shown to develop further in embryonic skin grafted to the chick chorioallantoic membrane (CAM). Recombinants of 12.5 day mouse epidermis with untreated or RA-treated mouse or chick dermis were then grafted to CAM for 7 days. For homospecific recombinants, 13.5 day mouse dermis originated from 11.5 day skin cultured for 2 days, with or without 5.2 microgram/ml RA. For heterospecific recombinants, 12 day dermis came from chick embryos, previously injected with 250 microgram RA. Glands were absent from the homospecific recombinants including untreated mouse dermis, but appeared in 26% of those with RA-treated dermis. Among heterospecific recombinants, 75% of those with RA-treated chick dermis and 29% of those with untreated dermis had glands. Untreated 10-12 day chick skin contained two forms of endogenous vitamin A, retinol (4.5 microgram/g protein) and dehydroretinol (3.7 microgram/g protein), while 13-14 day mouse skin contained only retinol (1.8 microgram/g protein), as shown by high performance liquid chromatography. RA injection increased retinol and dehydroretinol in chick skin, while RA was undetectable. Thus RA can act through mouse dermis to form epithelial glands and through chick dermis to increase the incidence of glands. The glands in recombinants with untreated chick dermis may result from the higher levels of endogenous retinoids in chick skin, compared with mouse skin.     

Fibroblast growth factors and their receptors: An information network controlling tissue growth,morphogenesis and repair

The stimulation of cellular metabolism by the nine fibroblast growth factors (FGFs) is mediated by a dual-receptor system. This comprises a family of four receptor tyrosine kinases (FGFR) and heparan sulphate proteoglycans (HSPG). The stimulation of cell division by FGFs has an obligate requirement for both partners of the dual-receptor system. The binding of the nine FGFs to the FGFRs is marked by a pattern of overlapping specificity despite alternative splicing events generating a large number of FGFR proteins. Thus many of the FGFR isoforms bind several FGFs. It is likely that each FGF requires a different pattern of sulphation within the heparan sulphate chains for binding. Therefore, the HSPG receptors may provide additional specificity, allowing a cell to fine tune its response to the FGFs present in the extracellular milieu. The HSPG receptors also control the availability of FGFs and hence regulate the transport of FGFs within a tissue. FGF-stimulated cell division would appear to have a mandatory requirement for the FGFs to be translocated to the nucleus via the cytosol after interacting with the dual-receptor system. The consequences of the potential direct action of FGFs in stimulating cell division are examined in the light of current models of signal transduction.