Search results for "Cell Lineage"
showing 10 items of 126 documents
Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity.
2008
Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear β-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling…
Cyclin E acts under the control of Hox-genes as a cell fate determinant in the developing central nervous system.
2005
The mechanisms controlling the generation of cell diversity in the central nervous system belong to the major unsolved problems in developmental biology. The fly Drosophila melanogaster is a suitable model system to examine these mechanisms at the level of individually identifiable cells. Recently, we have provided evidence that CyclinE--largely independent of its role in cell proliferation--plays a critical role in the specification of neural stem cells (neuroblasts). CycE specifies neuronal fate within neuroblast lineages by acting upstream of glial factors (prospero and glial cell missing), whereby levels of CycE are controlled by homeotic genes, the master control genes regulating segme…
A critical role for Cyclin E in cell fate determination in the central nervous system of Drosophila melanogaster
2004
We have examined the process by which cell diversity is generated in neuroblast (NB) lineages in the central nervous system of Drosophila melanogaster. Thoracic NB6-4 (NB6-4t) generates both neurons and glial cells, whereas NB6-4a generates only glial cells in abdominal segments. This is attributed to an asymmetric first division of NB6-4t, localizing prospero (pros) and glial cell missing (gcm) only to the glial precursor cell, and a symmetric division of NB6-4a, where both daughter cells express pros and gcm. Here we show that the NB6-4t lineage represents the ground state, which does not require the input of any homeotic gene, whereas the NB6-4a lineage is specified by the homeotic genes…
Compartmentalization of Central Neurons inDrosophila: A New Strategy of Mosaic Analysis Reveals Localization of Presynaptic Sites to Specific Segment…
2002
Synaptogenesis in the CNS has received far less attention than the development of neuromuscular synapses, although only central synapses allow the study of neuronal postsynaptic mechanisms and display a greater variety of structural and functional features. This neglect is attributable mainly to the enormous complexity of the CNS, which makes the visualization of individual synapses on defined neuronal processes very difficult. We overcome this obstacle and demonstrate by confocal microscopy the specific arrangement of output synapses on individual neurites. These studies are performed via genetic mosaic strategies in the CNS of the fruitfly Drosophila melanogaster. First, we use targeted e…
Spatio-temporal pattern of cells expressing the clock genes period and timeless and the lineages of period expressing neurons in the embryonic CNS of…
2010
The initial steps towards the generation of cell diversity in the central nervous system of the fruitfly Drosophila melanogaster take place during early phases of embryonic development when a stereotypic population of neural progenitor cells (neuroblasts and midline precursors) is formed in a precise spatial and temporal pattern, and subsequently expresses a particular sequence of genes. The clarification of the positional, temporal and molecular features of the individual progenitor cells in the nerve cord and brain as well as of their specific types of neuronal and/or glial progeny cells forms an essential basis to understand the mechanisms controlling their development. The present study…
Abdominal-A mediated repression of Cyclin E expression during cell-fate specification in the Drosophila central nervous system
2009
Homeotic/Hox genes are known to specify a given developmental pathway by regulating the expression of downstream effector genes. During embryonic CNS development of Drosophila, the Hox protein Abdominal-A (AbdA) is required for the specification of the abdominal NB6-4 lineage. It does so by down regulating the expression of the cell cycle regulator gene Dcyclin E (CycE). CycE is normally expressed in the thoracic NB6-4 lineage to give rise to mixed lineage of neurons and glia, while only glial cells are produced from the abdominal NB6-4 lineage due to the repression of CycE by AbdA. Here we investigate how AbdA represses the expression of CycE to define the abdominal fate of a single NB6-4 …
Mutations in spalt cause a severe but reversible neurodegenerative phenotype in the embryonic central nervous system ofDrosophila melanogaster
2002
The gene spalt is expressed in the embryonic central nervous system of Drosophila melanogaster but its function in this tissue is still unknown. To investigate this question, we used a combination of techniques to analyse spalt mutant embryos. Electron microscopy showed that in the absence of Spalt, the central nervous system cells are separated by enlarged extracellular spaces populated by membranous material at 60% of embryonic development. Surprisingly, the central nervous system from slightly older embryos (80% of development) exhibited almost wild-type morphology. An extensive survey by laser confocal microscopy revealed that thespalt mutant central nervous system has abnormal levels o…
Oligodendrogliogenic and neurogenic adult subependymal zone neural stem cells constitute distinct lineages and exhibit differential responsiveness to…
2012
The adult mouse subependymal zone (SEZ) harbours adult neural stem cells (aNSCs) that give rise to neuronal and oligodendroglial progeny. However it is not known whether the same aNSC can give rise to neuronal and oligodendroglial progeny or whether these distinct progenies constitute entirely separate lineages. Continuous live imaging and single-cell tracking of aNSCs and their progeny isolated from the mouse SEZ revealed that aNSCs exclusively generate oligodendroglia or neurons, but never both within a single lineage. Moreover, activation of canonical Wnt signalling selectively stimulated proliferation within the oligodendrogliogenic lineage, resulting in a massive increase in oligodendr…
Neuroblast pattern and identity in the Drosophila tail region and role of doublesex in the survival of sex-specific precursors.
2013
The central nervous system is composed of segmental units (neuromeres), the size and complexity of which evolved in correspondence to their functional requirements. In Drosophila, neuromeres develop from populations of neural stem cells (neuroblasts) that delaminate from the early embryonic neuroectoderm in a stereotyped spatial and temporal pattern. Pattern units closely resemble the ground state and are rather invariant in thoracic (T1-T3) and anterior abdominal (A1-A7) segments of the embryonic ventral nerve cord. Here, we provide a comprehensive neuroblast map of the terminal abdominal neuromeres A8-A10, which exhibit a progressively derived character. Compared with thoracic and anterio…
Composition of a Neuromere and Its Segmental Diversification under the Control ofHoxGenes in the Embryonic CNS ofDrosophila
2014
Studies performed at the level of single, identified cells in the fruitfly Drosophila have decisively contributed to our understanding of the mechanisms underlying the development and function of the nervous system. This review highlights some of the work based on single-cell analyses in the embryonic/larval CNS that sheds light on the principles underlying formation and organization of an entire segmental unit and its divergence along the anterior/posterior body axis.