Ventral neural tube cells differentiate into hepatocytes in the chick embryo

A population of ventral neural tube cells has recently been shown to migrate out of the hind brain neural tube via the vagus nerve and contribute to the developing gastrointestinal tract. Since liver is also innervated by the vagus nerve, we sought to determine if these cells also migrate into the liver. Ventral neural tube cells in the caudal hindbrain of chick embryos were tagged with a replication-deficient retroviral vector containing the LacZ gene on embryonic day 2. Embryos were processed for detection of labeled cells on embryonic day 5 and 11. Labeled cells were seen in the liver on both days and identified as hepatocytes. Previously, it was believed that all hepatocytes develop from the gut endoderm. Results of the present study show an additional source for the formation of liver cells. Received 25 August 1998; received after revision 5 November 1998; accepted 5 November 1998     

Evidence for reopening of the cranial neural tube in mouse embryos treated with cadmium chloride

Summary Use of the whole-embryo culture technique resulted in experiemtal evidence that the pathogenesis of exencephaly in mouse embryos after cadmium chloride treatment results from reopening of the cranial neural tube.     

Lipid droplets of neuroepithelial cells are a major calcium storage site during neural tube formation in chick and mouse embryos

In situ precipitation of calcium (Ca²⁺) with fluoride and antimonate shows that Ca²⁺-specific precipitate is localized almost exclusively within lipid droplets of neuroepithelial cells during neural tube formation in chick and mouse embryos. The density of Ca²⁺ precipitate within lipid droplets is generally greater in the apical ends of cells situated in regions of the neuroepithelium that are actively engaged in bending. These findings suggest that lipid droplets, in addition to providing a source of metabolic fuel for developing neuroepithelial cells, also serve as Ca²⁺-storage and-releasing sites during neurulation.This study was supported by grants from the NIH (NS23200), the BRSG fund of UMDNJ, and the Busch Fund of Rutgers University. Dr Bush was supported by a New Jersey State Postdoctoral Fellowship.     

Pleiotropic effects of sonic hedgehog on muscle satellite cells

Muscle satellite cells are believed to form a stable, self-renewing pool of stem cells in adult muscle where they function in tissue growth and repair. A regulatory disruption of growth and differentiation of these cells is assumed to result in tumor formation. Here we provide for the first time evidence that sonic hedgehog (Shh) regulates the cell fate of adult muscle satellite cells in mammals. Shh promotes cell division of satellite cells (and of the related model C2C12 cells) and prevents their differentiation into multinucleated myotubes. In addition, Shh inhibits caspase-3 activation and apoptosis induced by serum deprivation. These effects of Shh are reversed by simultaneous administration of cyclopamine, a specific inhibitor of the Shh pathway. Taken together, Shh acts as a proliferation and survival factor of satellite cells in the adult muscle. Our results support the hypothesis of the rhabdomyosarcoma origin from satellite cells and suggest a role for Shh in this process.Received 23 February 2005; received after revision 2 May 2005; accepted 9 June 2005     

Ras proteins in the control of the cell cycle and cell differentiation

The Ras family of small GTPases includes three closely related proteins: H-, K-, and N-Ras. Ras proteins are involved in the transduction of signals elicited by activated surface receptors, acting as key components by relaying signals downstream through diverse pathways. Mutant, constitutively activated forms of Ras proteins are frequently found in cancer. While constitutive Ras activation induces oncogenic-like transformation in immortalized fibroblasts, it causes growth arrest in primary vertebrate cells. Induction of p53 and cyclin-dependent kinase inhibitors such as p15^INK4b, p16^INK4a, p19^ARF, and p21^WAF1 accounts for this response. Interestingly, while ras has usually been regarded as a transforming oncogene, the analysis of Ras function in most of the cellular systems studied so far indicates that the promotion of differentiation is the most prominent effect of Ras. While in some cell types, particularly muscle, Ras inhibits differentiation, in others such as neuronal, adipocytic, or myeloid cells, Ras induces differentiation, in some cases accompanied by growth arrest. Several possible mechanisms for the pleiotropic effects of Ras in animal cells are discussed. Received 8 March 2000; received after revision 24 May 2000; accepted 24 May 2000     

Expression and function of galectin-1 in adult neural stem cells

Neural stem cells (NSCs) in the adult mammalian brain proliferate and continuously produce new neurons. To date, there has been little research into the functions of lectins in adult NSCs. Recently, we reported that a lectin, galectin-1, is expressed on adult NSCs and promotes their proliferation through its carbohydrate-binding ability. This evidence raises the possibility that glycans play roles in the proliferation of adult NSCs. Received 6 November 2006; received after revision 13 December 2006; accepted 15 February 2007     

The role of glycosylation in protein antigenic properties

Glycosylation of proteins is a common event and contributes to protein antigenic properties. Most data have been obtained from model studies on glycoprotens with well-defined structure or synthetic glycopeptides and their respective monoclonal antibodies. Antibodies raised against glycoprotein antigens may be specific for their carbohydrate units which are recognized irrespective of the protein carrier (carbohydrate epitopes), or in the context of the adjacent amino acid residues (glycopeptidic epitopes). Conformation or proper exposure of peptidic epitopes of glycoproteins is also frequently modulated by glycosylation due to intramolecular carbohydrate-protein interactions. The effects of glycosylation are broad: glycosylation may 'inactivate' the peptidic epitope or may be required for its reactivity with the antibody, depending on the structure of the antigenic site and antibody fine specificity. Evidence is increasing that similar effects of glycosylation pertain to T cell-dependent cellular immune responses. Glycosylated peptides can be bound and presented by MHC class I or II molecules and elicit glycopeptide-specific T cell clones. Received 5 July 2001; received after revision 9 October 2001; accepted 11 October 2001     

The regulation of embryonic patterning and DNA replication by geminin

Geminin is a multifunctional protein. After DNA replication is initiated during a cell cycle, geminin binds to Cdt1, one of the key DNA replication licensing factors. This highly regulated interaction sequestrates Cdt1, thus preventing DNA rereplication in the same cell cycle. In addition, geminin directly interacts with Six3 and Hox homeodomain proteins during embryogenesis and inhibits their functions. The regulation of Hox function by geminin also involves a transient association with the Hox repressive Polycomb complex. The functions of geminin to obstruct key molecules of both cell proliferation and embryonic development suggest a competitive coordination of these two processes.Received 10 December 2004; received after revision 27 January 2005; accepted March 2005     

ABCA2: a candidate regulator of neural transmembrane lipid transport

Studies in the past years have implicated multispan transmembrane transport molecules of the ATP binding cassette (ABC) transporter family in cellular lipid export processes. The prototypic ABC transporter ABCA1 has recently been demonstrated to act as a major facilitator of cellular cholesterol and phospholipid export. Moreover, the transporter ABCA4 (ABCR) plays a pivotal role in retinaldehyde processing, and ABCA3 has recently implicated in lung surfactant processing. These pioneering observations have directed considerable attention to the A subfamily of ABC proteins. ABCA2 is the codefining member of the ABC A-transporter subclass. Although known for some time, it was not until recently that its complete molecular structure was established. Unlike other ABC A-subfamily members, ABCA2 is predominantly expressed in the brain and neural tissues. The unique expression profile together with available structural data suggest roles for this largest known ABC protein in neural transmembrane lipid export. Received 31 January 2002; received after revision 11 March 2002; accepted 11 March 2002     

The role of thrombospondin-1 in apoptosis

The thrombospondins are a family of extracellular proteins that participate in cell-to-cell and cell-to-matrix communication. They regulate cellular phenotype during tissue genesis and repair. Five family members, each representing a separate gene product, probably exist in most vertebrate species. Like most extracellular proteins, the thrombospondins are composed of several structural domains that are responsible for the numerous biological functions that have been described for this protein family. Considerable progress has been made towards understanding the function of thrombospondins. The role of thrombospondin in the process of apoptosis or programmed cell death has recently come into focus. In this review we will concentrate on the role of thrombospondin-1 in the broad field of apoptotis research. Received 5 December 2001; received after revision 28 March 2002; accepted 28 March 2002     

Role of extracellular matrix molecules in the development of the sodium current in quail mesencephalic neural crest cells

The occurrence of the voltage-dependent sodium current has been studied in developing neurons from quail mesencephalic neural crest on different substrates, using the whole-cell patch clamp technique. Explants from 9–12 somite embryos were cultured on dishes coated with type I collagen, fibronectin, laminin or on plastic dishes in a chemically defined medium. After 18 h of culture the sodium current was observed in 70% of the neurons tested, and at 24 h some of these neurons were able to generate an action potential. After 18–25 h cells grown on fibronectinor collagen I-coated dishes showed a significantly higher occurrence of the sodium current (83% and 84% respectively) as compared to cells grown on uncoated plastic dishes (51%). Moreover, in the presence of fibronectin, the current density of the sodium current was more than doubled in comparison with cells grown on other substrates.     

The Ror receptor tyrosine kinase family

Receptor tyrosine kinases (RTKs) participate in numerous developmental decisions. Ror RTKs are a family of orphan receptors that are related to muscle specific kinase (MuSK) and Trk neurotrophin receptors. MuSK assembles acetylcholine receptors at the neuromuscular junction [1, 2], and Trk receptors function in the developing nervous system (reviewed in [3-5]). Rors have been identified in nematodes, insects and mammals. Recent studies have begun to shed light on Ror function during development. In most species, Rors are expressed in many tissue types during development. Analyses of mutants that are defective in the single nematode Ror demonstrate a role in cell migration and in orienting cell polarity. Mice lacking one of the two Ror gene products display defects in bone and heart formation. Similarly, two different human bone development disorders, dominant brachydactyly B and recessive Robinow syndrome, result from mutations in one of the human Ror genes. Received 17 April 2001; received after revision 2 July 2001; accepted 4 July 2001     

The effects of ethanol on embryonic actin: A possible role in teratogenesis

Summary When the neural crest is cultured in the long or short term presence of ethanol, monoclonal anti-actin reveals the development of a disorganized actin cytoskeleton. In the long term, many cells fail to differentiate morphologically, whereas in the short term already differentiated cells rapidly alter their shape and their cell-to-cell contacts.     

The role of perireceptor events in vertebrate olfaction

The perception of odours and pheromones is mediated by small soluble carrier proteins that belong to the family of lipocalins. Those secreted by the nasal mucosa are called odorant-binding proteins (OBPs) for their binding activity towards volatile compounds. Proteins of similar structure, which we call pheromone-binding proteins (PBPs), help to deliver volatile pheromones in the environment. They are present in high concentration in biological fluids, such as urine, saliva and vaginal discharge, involved in chemical communication between conspecifics. Several subclasses of OBPs have been identified in the same animal species, each best related to a particular group of PBPs. Such similarities, together with anatomical and behavioural evidence, suggest that OBPs may be involved in the perception of pheromones.     

Wnt signaling: multiple functions in neural development

Wnt signaling has proven to be essential for neural development at various stages and across species. Wnts are involved in morphogenesis and patterning, and their proliferation-promoting role is a key function in stem cell maintenance and the expansion of progenitor pools. Moreover, Wnt signaling is involved in differentiation processes and lineage decision events during both central and peripheral nervous system development. Additionally, several reports point to a role of Wnt signaling in axon guidance and neurite outgrowth. This article reviews and consolidates the existing evidence for the functions of Wnt signaling in neural development.Received 10 December 2004; received after revision 19 January 2005; accepted 21 January 2005     

The role of repair in radiobiology

Summary Apart from cancer and mutation induction, radiobiological effects on mammals are mostly attributable to cell death, defined as loss of proliferative capacity. Survival curves relate retention of that capacity to radiation dose, and often manifest a quasi-threshold (shoulder). The shoulder is attributable to an initial mechanism of repair (Q-repair) which is gradually depleted as dose increases. Another form of repair, which is not depleted (P-repair), increases the dose required to deliver an average of one lethal event per cell (dose D₀). Neither form of repair can unambiguously be linked with repair of defects in isolated DNA. An important initial lesion may well be disruption of the complex structural relationship between the DNA, nuclear membrane and associated proteins. One form of P-repair may be restoration of that structural relationship.     

Insights into autotransplantation: the unexpected discovery of specific induction systems in bone marrow stromal cells

Many kinds of cells, including embryonic stem cells and tissue stem cells, have been considered candidates for transplantation therapy for neuro- and muscle-degenerative diseases. Bone marrow stromal cells (MSCs) also have great potential as therapeutic agents since they are easily isolated and can be expanded from patients without serious ethical or technical problems. Recently, new methods for the highly efficient and specific induction of functional neurons and skeletal muscle cells have been developed for MSCs. These induced cells were transplanted into animal models of stroke, Parkinson’s disease and muscle degeneration, resulting in the successful integration of transplanted cells and improvement in the behavior of the transplanted animals. Here I describe the discovery of these induction systems and focus on the potential use of MSC-derived cells for ‘auto-cell transplantation therapy’ in neuro- and muscle-degenerative diseases. Received 27 April 2006; received after revision 5 June 2006; accepted 22 August 2006