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M Placzek

Publications and source records attributed to M Placzek.

At least 37 records · Page 2Linked to original sources

A role for SOX1 in neural determination.

In vertebrates, the delineation of the neural plate from a region of the primitive ectoderm is accompanied by the onset of specific gene expression which in turn promotes the formation of the nervous system. Here we show that SOX1, an HMG-box protein related to SRY, is one of the earliest transcription factors to be expressed in ectodermal cells committed to the neural fate: the onset of expression of SOX1 appears to coincide with the induction of neural ectoderm. We demonstrate a role for SOX1 in neural determination and differentiation using an inducible expression P19 cell system as an in vitro model of neurogenesis. Misexpression of SOX1 can substitute for the requirement of retinoic acid to impart neural fate to competent ectodermal P19 cells. Using a series of antigenic markers which identify early neural cell types in combination with BrdU labeling, we demonstrate a temporal and spatial correlation between the differentiation of cell types along the dorsoventral axis of the neural tube and the downregulation of SOX1 expression. SOX1, therefore, defines the dividing neural precursors of the embryonic central nervous system (CNS).

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Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells by prechordal mesoderm.

Ventral midline cells at different rostrocaudal levels of the central nervous system exhibit distinct properties but share the ability to pattern the dorsoventral axis of the neural tube. We show here that ventral midline cells acquire distinct identities in response to the different signaling activities of underlying mesoderm. Signals from prechordal mesoderm control the differentiation of rostral diencephalic ventral midline cells, whereas notochord induces floor plate cells caudally. Sonic hedgehog (SHH) is expressed throughout axial mesoderm and is required for the induction of both rostral diencephalic ventral midline cells and floor plate. However, prechordal mesoderm also expresses BMP7 whose function is required coordinately with SHH to induce rostral diencephalic ventral midline cells. BMP7 acts directly on neural cells, modifying their response to SHH so that they differentiate into rostral diencephalic ventral midline cells rather than floor plate cells. Our results suggest a model whereby axial mesoderm both induces the differentiation of overlying neural cells and controls the rostrocaudal character of the ventral midline of the neural tube.

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Patterning cascades in the neural tube. Neural development.

The vertebrate central nervous system comprises an intricate array of neurons generated in a highly organized way. Examination of the genes expressed and required at early stages of neural differentiation reveals that a coordinated signalling cascade transforms progenitor cells into discrete neuronal subsets.

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Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube.

The vertebrate hedgehog-related gene Sonic hedgehog (Shh) is expressed in ventral domains along the entire rostrocaudal length of the neural tube, including the forebrain. We show here that SHH induces the differentiation of ventral neuronal cell types in explants derived from prospective forebrain regions of the neural plate. Neurons induced in explants derived from both diencephalic and telencephalic levels of the neural plate express the LIM homeodomain protein Isl-1, and these neurons possess distinct identities that match those of the ventral neurons generated in these two subdivisions of the forebrain in vivo. A single inducing molecule, SHH, therefore appears to mediate the induction of distinct ventral neuronal cell types along the entire rostrocaudal extent of the embryonic central nervous system.

Activated-Leukocyte Cell Adhesion Molecule↗

Early stages of notochord and floor plate development in the chick embryo defined by normal and induced expression of HNF-3 beta.

We have cloned a cDNA encoding the chick HNF-3 beta gene and have used RNA and antibody probes that detect HNF-3 beta to monitor the normal and induced expression of the gene in early embryos. HNF-3 beta expressed in Koller's sickle, at the onset of primitive streak formation, and later in Hensen's node. At neural plate and neural tube stages, HNF-3 beta is expressed transiently in the notochord and is then expressed by floor plate cells. Prospective floor plate cells that are located in the epiblast immediately anterior to Hensen's node prior to its regression do not express HNF-3 beta, providing evidence that floor plate fate is normally determined only after these cells populate the midline of the neural plate and overlie the notochord. Removal of the notochord in vivo prevents floor plate development and in this condition HNF-3 beta is not expressed by cells at the ventral midline of the neural tube. Notochord grafts induce ectopic floor plate development and ectopic neural expression of HNF-3 beta. In vitro, neural plate explants are induced to express HNF-3 beta by notochord cells in a contact-dependent but cycloheximide-resistant manner, providing evidence that expression of HNF-3 beta is a direct response of neural plate cells to notochord-derived inducing signals.

Amino Acid Sequence↗

The role of the notochord and floor plate in inductive interactions.

Recent studies have uncovered new roles for the notochord and floor plate in patterning adjacent cells, elaborating their importance as essential organizers of neural and paraxial tissue. The identification of key molecules that mediate the ability of notochord and floor plate to induce cells to adopt distinct fates has provided a first step in elucidating the mechanisms underlying these events.

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S fimbriae of uropathogenic Escherichia coli bind to primary human renal proximal tubular epithelial cells but do not induce expression of intercellular adhesion molecule 1.

We have recently reported an increase of expression of the intercellular adhesion molecule 1 by renal carcinoma cells in response to S fimbriae of Escherichia coli. Now we demonstrate that E. coli expressing S and P fimbriae strongly binds to human proximal tubular epithelial cells. However, in primary and simian virus 40-transfected renal tubular epithelial cells S fimbriae do not enhance the expression of intercellular adhesion molecule 1.

Bacterial Adhesion↗

Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord.

The differentiation of distinct cell types in the ventral neural tube depends on local inductive signals from the notochord. We have isolated a vertebrate homolog of the Drosophila segment polarity gene hedgehog (hh) from zebrafish and rat, termed vhh-1. vhh-1 is expressed in the node, notochord, floor plate, and posterior limb bud mesenchyme. Each of these cell groups has floor plate inducing activity, suggesting that the vhh-1 gene may encode a floor plate-inducing molecule. Widespread expression of rat vhh-1 in frog embryos leads to ectopic floor plate differentiation in the neural tube. In vitro tests for the signaling functions of vhh-1 demonstrate that COS cells expressing the rat vhh-1 gene induce floor plate and motor neuron differentiation in neural plate explants. vhh-1 may, therefore, contribute to the floor plate and motor neuron inducing activities of the notochord.

Amino Acid Sequence↗

Border disputes: do boundaries play a role in growth-cone guidance?

One of the earliest indications of regional patterning in the CNS is the spatially restricted expression of regulatory genes within the neuroepithelium. Many of these genes encode transcription factors and, although little is known of their downstream targets, it seems likely that they control the identity of cells in different regions of the CNS. This review discusses how the expression of these patterning genes might influence the location at which the first axon pathways in the CNS are pioneered. Evidence is described that suggests that the boundary regions between adjacent domains of regulatory gene expression influence where the first axons will extend.

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Nasal endotracheal intubation in a premature infant with a nasal encephalocele.

After a difficult nasal intubation a premature infant leaked cerebrospinal fluid (CSF) from one nostril. After developing bacterial meningitis, the baby was referred for neurosurgical management of the CSF fistula. Transaxial computed tomograms demonstrated a nasal encephalocele, but coronal scans were needed to show the defect in the cribriform plate.

Brain↗

Induction of floor plate differentiation by contact-dependent, homeogenetic signals.

The floor plate is located at the ventral midline of the neural tube and has been implicated in neural cell patterning and axon guidance. To address the cellular mechanisms involved in floor plate differentiation, we have used an assay that monitors the expression of floor-plate-specific antigens in neural plate explants cultured in the presence of inducing tissues. Contact-mediated signals from both the notochord and the floor plate act directly on neural plate cells to induce floor plate differentiation. Floor plate induction is initiated medially by a signal from the notochord, but appears to be propagated to more lateral cells by homeogenetic signals that derive from medial floor plate cells. The response of neural plate cells to inductive signals declines with embryonic age, suggesting that the mediolateral extent of the floor plate is limited by a loss of competence of neural cells. The rostral boundary of the floor plate at the midbrain-forebrain junction appears to result from the lack of inducing activity in prechordal mesoderm and the inability of rostral neural plate cells to respond to inductive signals.

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Control of cell pattern in the developing nervous system: polarizing activity of the floor plate and notochord.

Individual classes of neural cells differentiate at distinct locations in the developing vertebrate nervous system. We provide evidence that the pattern of cell differentiation along the dorsoventral axis of the chick neural tube is regulated by signals derived from two ventral midline cell groups, the notochord and floor plate. Grafting an additional notochord or floor plate to ectopic positions, or deleting both cell groups, resulted in changes in the fate and position of neural cell types, defined by expression of specific antigens. These results suggest that the differentiation of neural cells is controlled, in part, by their position with respect to the notochord and floor plate.

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Target attraction: are developing axons guided by chemotropism?

A century has elapsed since Ramón y Cajal proposed his chemotropic theory of axon guidance, i.e. the attraction of developing axons by diffusible molecules emanating from their targets. Although the precise contribution of axonal chemoattractants to guidance in vivo remains to be established, two lines of investigation have provided evidence for their existence and importance. First, concentration gradients of nerve growth factor (NGF) have been shown to orient the growth of regenerating sensory axons in vitro. Although NGF does not appear to guide axons during development, these studies show that growth cones can orient in gradients of diffusible molecules. Second, the cellular targets of several different classes of developing neurons have been shown to secrete as yet unidentified diffusible factors that can orient axons. We review these studies and discuss the potential contribution of chemotropism to the establishment of axonal projection patterns in vertebrates.

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Control of dorsoventral pattern in vertebrate neural development: induction and polarizing properties of the floor plate.

Distinct classes of neural cells differentiate at specific locations within the embryonic vertebrate nervous system. To define the cellular mechanisms that control the identity and pattern of neural cells we have used a combination of functional assays and antigenic markers to examine the differentiation of cells in the developing spinal cord and hindbrain in vivo and in vitro. Our results suggest that a critical step in the dorsoventral patterning of the embryonic CNS is the differentiation of a specialized group of midline neural cells, termed the floor plate, in response to local inductive signals from the underlying notochord. The floor plate and notochord appear to control the pattern of cell types that appear along the dorsoventral axis of the neural tube. The fate of neuroepithelial cells in the ventral neural tube may be defined by cell position with respect to the ventral midline and controlled by polarizing signals that originate from the floor plate and notochord.

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Mesodermal control of neural cell identity: floor plate induction by the notochord.

The floor plate is a specialized group of midline neuroepithelial cells that appears to regulate cell differentiation and axonal growth in the developing vertebrate nervous system. A floor plate-specific chemoattractant was used as a marker to examine the role of the notochord in avian floor plate development. Expression of this chemoattractant in lateral cells of the neural plate and neural tube was induced by an ectopic notochord, and midline neural tube cells did not express the chemoattractant after removal of the notochord early in development. These results provide evidence that a local signal from the notochord induces the functional properties of the floor plate.

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Orientation of commissural axons in vitro in response to a floor plate-derived chemoattractant.

Developing axons are guided to their targets by molecular cues in their local environment. Some cues are short-range, deriving from cells along axonal pathways. There is also increasing evidence for longer-range guidance cues, in the form of gradients of diffusible chemoattractant molecules, which originate from restricted populations of target cells. The guidance of developing commissural axons within the spinal cord depends on one of their intermediate cellular targets, the floor plate. We have shown previously that floor plate cells secrete a diffusible factor(s) that can alter the direction of commissural axon growth in vitro. Here we show that the factor is an effective chemoattractant for commissural axons. It can diffuse considerable distances through a collagen gel matrix and through dorsal and ventral neural epithelium in vitro to reorient the growth of virtually all commissural axons. The orientation of axons occurs in the absence of detectable effects on the survival of commissural neurons or on the rate of commissural axon extension. The regionally restricted expression of the factor suggests that it is present in the embryonic spinal cord in a gradient with its high point at the floor plate. These observations support the idea that the guidance of commissural axons to the ventral midline of the spinal cord results in part from the secretion of a chemoattractant by the floor plate.

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Polarity and patterning in the neural tube: the origin and function of the floor plate.

Little is known about the cellular and molecular mechanisms that determine neuronal cell fate and the patterning of neuronal connections in the vertebrate central nervous system. In this paper we summarize evidence which indicates that some aspects of neuronal differentiation and axon guidance are regulated by specialized epithelial cells that occupy the medial region of the neural plate and, later, the ventral midline of the spinal cord. This cell group, termed the notoplate/floor plate appears to constitute a distinct compartment within the neural plate that is more closely related in lineage and perhaps also in function to axial mesodermal cells of the underlying notochord than to other neural plate cells. Cells of the notoplate exhibit specialized mechanical and adhesive properties that may contribute to neurulation. At later stages of development, the floor plate appears to guide developing axons in the embryonic spinal cord by releasing a diffusible chemoattractant factor and by virtue of its specialized cell surface properties. The floor plate may also play a role in the determination of cell identity and patterning at earlier stages of neural tube development.

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