Search results for "cell fate"

Optimal control circuitry design for the digital p53 dynamics in cancer cell and apoptosis

2009

AbstractExperimental work and theoretical models deduce a "digital" response of the p53 transcription factor when genomic integrity is damaged. The mutual influence of p53 and its antagonist, the Mdm2 oncogene, is closed in feedback. This paper proposes an aerospace architecture for translating the p53/Mdm2/DNA damage network into a digital circuitry in which the optimal control theory is applied for obtaining the requested dynamic evolutions of some considered cell species for repairing a DNA damage. The purpose of this paper is not to improve the analysis of the actual mathematical models but to demonstrate the usefulness of such digital circuitry design capable to predict and detect the …

Dorsoventral Patterning of the Brain: A Comparative Approach

2009

Development of the central nervous system (CNS) involves the transformation of a two-dimensional epithelial sheet of uniform ectodermal cells, the neuroectoderm, into a highly complex three-dimensional structure consisting of a huge variety of different neural cell types. Characteristic numbers of each cell type become arranged in reproducible spatial patterns, which is a prerequisite for the establishment of specific functional contacts. Specification of cell fate and regional patterning critical depends on positional information conferred to neural stem cells early in the neuroectoderm. This chapter compares recent findings on mechanisms that control the specification of cell fates along …

Identity, origin, and migration of peripheral glial cells in the Drosophila embryo.

2008

Glial cells are crucial for the proper development and function of the nervous system. In the Drosophila embryo, the glial cells of the peripheral nervous system are generated both by central neuroblasts and sensory organ precursors. Most peripheral glial cells need to migrate along axonal projections of motor and sensory neurons to reach their final positions in the periphery. Here we studied the spatial and temporal pattern, the identity, the migration, and the origin of all peripheral glial cells in the truncal segments of wildtype embryos. The establishment of individual identities among these cells is reflected by the expression of a combinatorial code of molecular markers. This allows…

The Embryonic Central Nervous System Lineages ofDrosophila melanogaster

1997

Abstract In Drosophila, central nervous system (CNS) formation starts with the delamination from the neuroectoderm of about 30 neuroblasts (NBs) per hemisegment. They give rise to approximately 350 neurons and 30 glial cells during embryonic development. Understanding the mechanisms leading to cell fate specification and differentiation in the CNS requires the identification of the NB lineages. The embryonic lineages derived from 17 NBs of the ventral part of the neuroectoderm have previously been described (Bossing et al., 1996). Here we present 13 lineages derived from the dorsal part of the neuroectoderm and we assign 12 of them to identified NBs. Together, the 13 lineages comprise appro…

Competence of blastomeres for the expression of molecular tissue markers is acquired by diverse mechanisms in the embryo of Platynereis (Annelida)

1992

This paper is devoted to the role of cell divisions for the establishment of histospecificity in the embryo of the spiralian, Platynereis dumerilii (Annelida). We have incubated successive cleavage stages in cytochalasin B (CCB) and observed whether the cells thereafter were able to acquire the competence for expressing histospecific antigens of larval gland cells (labelled by the monoclonal antibody OI64) and of neural components of the ventral nerve cord (labelled by mAb OI7 or by testing acety1cholinesterase activity), respectively. Incubation in CCB results in permanent cleavage arrest, but does not necessarily interfere with biochemical differentiation of such markers. Synthesis of the…

2013

Cortical function is impaired in various disorders of the central nervous system including Alzheimer’s disease, autism and schizophrenia. Some of these disorders are speculated to be associated with insults in early brain development. Pericytes have been shown to regulate neurovascular integrity in development, health and disease. Hence, precisely controlled mechanisms must have evolved in evolution to operate pericyte proliferation, repair and cell fate within the neurovascular unit (NVU). It is well established that pericyte deficiency leads to NVU injury resulting in cognitive decline and neuroinflammation in cortical layers. However, little is known about the role of pericytes in pathop…

Cell fate regulation upon DNA damage : p53 Serine 46 kinases pave the cell death road

2019

Mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the tumor suppressor p53 directs the cellular response to cell cycle arrest, DNA repair, and cell survival, whereas upon severe damage, p53 drives the cell death response. One posttranslational modification of p53, phosphorylation at Serine 46, selectively occurs after severe DNA damage and is envisioned as a marker of the cell death response. However, the molecular mechanism of action of the p53 Ser46 phospho-isomer, the molecular timing of this phosphorylation event, and its activating effects on apoptosis and ferropt…

Role Of S-Nitrosylation In The Extrinsic Apoptotic Signalling Pathway In Cancer.

2015

One of the key features of tumour cells is the acquisition of resistance to apoptosis. Thus, determining therapeutic strategies that circumvent apoptotic resistance and result in tumor regression is a challenge. One strategy to induce apoptosis is to activate death receptor signalling pathways. Members of the Tumor Necrosis Factor TNF-family death receptors ligand (TRAIL, FasL and TNF-α) can originate from immune and non-immune cells. Death receptors, engaged by cognate ligands, can initiate multiple signaling pathways, which can generate diverse outcomes, including non-apoptosis-related signal. Knowledge on the molecular mechanisms (that determine death or survival of tumour cells) followi…

Cell cycle independent role of Cyclin E during neural cell fate specification in Drosophila is mediated by its regulation of Prospero function

2009

AbstractDuring development, neural progenitor cells or neuroblasts generate a great intra- and inter-segmental diversity of neuronal and glial cell types in the nervous system. In thoracic segments of the embryonic central nervous system of Drosophila, the neuroblast NB6-4t undergoes an asymmetric first division to generate a neuronal and a glial sublineage, while abdominal NB6-4a divides once symmetrically to generate only 2 glial cells. We had earlier reported a critical function for the G1 cyclin, CyclinE (CycE) in regulating asymmetric cell division in NB6-4t. Here we show that (i) this function of CycE is independent of its role in cell cycle regulation and (ii) the two functions are m…

Peptides Derived from the Transmembrane Domain of Bcl-2 Proteins as Potential Mitochondrial Priming Tools

2014

The Bcl-2 family of proteins is crucial for apoptosis regulation. Members of this family insert through a specific C-terminal anchoring trans membrane domain (TMD) in the mitochondrial outer membrane where they hierarchically interact to determine cell fate. While the mitochondrial membrane has been proposed to actively participate in these protein protein interactions, the influence of the TMD in the membrane-mediated interaction is poorly understood. Synthetic peptides (TMD-pepts) corresponding to the putative TMD of antiapoptotic (Bcl-2, Bcl-xL, Bcl-w, and Mcl-1) and pro-apoptotic (Bax, Bak) members were synthesized and characterized. TMD-pepts bound more efficiently to mitochondria-like…