Extrinsic Cues (extrinsic + cue)

Distribution by Scientific Domains


Selected Abstracts


Glutamate regulates retinal progenitors cells proliferation during development

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006
Rodrigo A. P. Martins
Abstract The precise coordination of cell cycle exit and cell fate specification is essential for generating the correct proportion of retinal cell types during development. The decision to exit the cell cycle is regulated by intrinsic and extrinsic cues. There is growing evidence that neurotransmitters can regulate cell proliferation and cell fate specification during the early stages of CNS development prior to the formation of synaptic connections. We found that the excitatory neurotransmitter glutamate regulates retinal progenitor cell proliferation during embryonic development of the mouse. AMPA/kainate and N -methyl- d -aspartate receptors are expressed in embryonic retinal progenitor cells. Addition of exogenous glutamate leads to a dose-dependent decrease in cell proliferation without inducing cell death or activating the p53 pathway. Activation of AMPA/kainate receptors induced retinal progenitor cells to prematurely exit the cell cycle. Using a replication-incompetent retrovirus to follow the clonal expansion of individual retinal progenitor cells, it was observed that blockade of AMPA/kainate receptors increased the proportion of large clones, showing that modulation of endogenous glutamatergic activity can have long-term consequences on retinal cell proliferation. Real time reverse transcriptase-polymerase chain reaction and immunoblot analyses demonstrated that glutamate does not alter the levels of the mRNA and proteins that regulate the G1/S-phase transition. Instead, the activity of the Cdk2 kinase is reduced in the presence of glutamate. These data indicate that glutamate regulates retinal progenitor cell proliferation by post-translational modulation of cyclin/Cdk2 kinase activity. [source]


A role of local signalling in the establishment and maintenance of the asymmetrical architecture of a neuron

JOURNAL OF NEUROCHEMISTRY, Issue 3 2007
Eun-Mi Hur
Abstract Significant progress has been made in the identification of intrinsic and extrinsic factors involved in the development of nervous system. It is remarkable that the establishment and maintenance of the asymmetrical architecture of a neuron is coordinated by a limited repertoire of signalling machineries. However, the details of signalling mechanisms responsible for creating specificity and diversity required for proper development of the nervous system remain largely to be investigated. An emerging body of evidence suggests that specificity and diversity can be achieved by differential regulation of signalling components at distinct subcelluar localizations. Many aspects of neuronal polarization and morphogenesis are attributed to localized signalling. Further diversity and specificity of receptor signalling can be achieved by the regulation of molecules outside the cell. Recent evidence suggests that extracellular matrix molecules are essential extrinsic cues that function to foster the growth of neurons. Therefore, it is important to understand where the signalling machineries are activated and how they are combined with other factors in order to understand the molecular mechanism underlying neuronal development. [source]


Generation of spinal motor neurons from human fetal brain-derived neural stem cells: Role of basic fibroblast growth factor

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009
Paivi M. Jordan
Abstract Neural stem cells (NSCs) have some specified properties but are generally uncommitted and so can change their fate after exposure to environmental cues. It is unclear to what extent this NSC plasticity can be modulated by extrinsic cues and what are the molecular mechanisms underlying neuronal fate determination. Basic fibroblast growth factor (bFGF) is a well-known mitogen for proliferating NSCs. However, its role in guiding stem cells for neuronal subtype specification is undefined. Here we report that in-vitro-expanded human fetal forebrain-derived NSCs can generate cholinergic neurons with spinal motor neuron properties when treated with bFGF within a specific time window. bFGF induces NSCs to express the motor neuron marker Hb9, which is blocked by specific FGF receptor inhibitors and bFGF neutralizing antibodies. This development of spinal motor neuron properties is independent of selective proliferation or survival and does not require high levels of MAPK activation. Thus our study indicates that bFGF can play an important role in modulating plasticity and neuronal fate of human NSCs and presumably has implications for exploring the full potential of brain NSCs for clinical applications, particularly in spinal motor neuron regeneration. © 2008 Wiley-Liss, Inc. [source]


Haematopoietic stem cell niche in Drosophila

BIOESSAYS, Issue 8 2007
Ute Koch
Development and homeostasis of the haematopoietic system is dependent upon stem cells that have the unique ability to both self-renew and to differentiate in all cell lineages of the blood. The crucial decision between haematopoietic stem cell (HSC) self-renewal and differentiation must be tightly controlled. Ultimately, this choice is regulated by the integration of intrinsic signals together with extrinsic cues provided by an exclusive microenvironment, the so-called haematopoietic niche. Although the haematopoietic system of vertebrates has been studied extensively for many decades, the specification of the HSC niche and its signals involved are poorly understood. Much of our current knowledge of how niches regulate long-term maintenance of stem cells is derived from studies on Drosophila germ cells. Now, two recently published studies by Mandal et al.1 and Krezmien et al.2 describe the Drosophila haematopoietic niche and signal transduction pathways that are involved in the maintenance of haematopoietic precursors. Both reports emphasize several features that are important for controlling stem cell behavior and show parallels to both the vertebrate haematopoietic niche as well as the Drosophila germline stem cell niches in ovary and testis. The findings of both papers shed new light on the specific interactions between haematopoietic progenitors and their microenvironment. BioEssays 29:713,716, 2007. © 2007 Wiley Periodicals, Inc. [source]