Control of cell division in the adult brain by heparan sulfates in fractones and vascular basement membranes

Regulation of cell division in adult tissues and organs requires the coordination of growth factors at the surface of potentially-dividing cells in specific anatomic loci named germinal niches. However, the biological components and physiological system that control growth factors in the germinal niches are unknown. In the adult brain, no function has been attributed to fractones, the fractal-shaped extracellular matrix structures located in the subventricular zone (SVZ) next to neural stem and progenitor cells. Here, we show that BMP-7 (bone morphogenetic protein-7) and FGF-2 (fibroblast growth factor-2) modulate cell division in the SVZ only if the growth factors bind to heparan sulfates localized in fractones and adjoined vascular basement membranes. Our results strongly suggest that fractones and specialized basement membranes function as stem cell niche structures, capturing and potentiating growth factors to regulate cell division in the adult brain

Etude de la machinerie de sécrétion de type II et de son implication dans le métabolisme du fer chez Erwinia chrysanthemi

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF

Erwinia chrysanthemi Iron Metabolism: the Unexpected Implication of the Inner Membrane Platform within the Type II Secretion System▿ †

The type II secretion (T2S) system is an essential device for Erwinia chrysanthemi virulence. Previously, we reported the key role of the OutF protein in forming, along with OutELM, an inner membrane platform in the Out T2S system. Here, we report that OutF copurified with five proteins identified by matrix-assisted laser desorption ionization-time of flight analysis as AcsD, TogA, SecA, Tsp, and DegP. The AcsD protein was known to be involved in the biosynthesis of achromobactin, which is a siderophore important for E. chrysanthemi virulence. The yeast two-hybrid system allowed us to gain further evidence for the OutF-AcsD interaction. Moreover, we showed that lack of OutF produced a pleiotropic phenotype: (i) altered production of the two siderophores of E. chrysanthemi, achromobactin and chrysobactin; (ii) hypersensitivity to streptonigrin, an iron-activated antibiotic; (iii) increased sensitivity to oxidative stress; and (iv) absence of the FbpA-like iron-binding protein in the periplasmic fraction. Interestingly, outE and outL mutants also exhibited similar phenotypes, but, outD and outJ mutants did not. Moreover, using the yeast two-hybrid system, several interactions were shown to occur between components of the T2S system inner membrane platform (OutEFL) and proteins involved in achromobactin production (AcsABCDE). The OutL-AcsD interaction was also demonstrated by Ni2+ affinity chromatography. These results fully confirm our previous view that the T2S machinery is made up of three discrete blocks. The OutEFLM-forming platform is proposed to be instrumental in two different processes essential for virulence, protein secretion and iron homeostasis

Dynamic mathematical modeling of cell-fractone interactions

MI: Global COE Program Education-and-Research Hub for Mathematics-for-IndustryグローバルCOEプログラム「マス･フォア･インダストリ教育研究拠点」Within the last 20 years, new biological structures called fractones, named in honor of the late Dr. Benoit Mandelbrot due to their fractal-like appearance, have been discovered by cell biologists. Their primary purposes are theorized to pertain to the major processes of the life cycle of cells, namely cell division, migration, and differentiation. Building on the back of the discretized diffusion equations, we built a mathematical model of how these fractones interact with the cells and the associated growth factors produced in order to gain insight into the growth process as a whole. As it is shown in this paper, the complexity of this biological process opens the door to entirely new questions in the field of control theory

Dynamic mathematical modeling of cell-fractone interactions

Within the last 20 years, new biological structures called fractones, named in honor of the late Dr. Benoit Mandelbrot due to their fractal-like appearance, have been discovered by cell biologists. Their primary purposes are theorized to pertain to the major processes of the life cycle of cells, namely cell division, migration, and differentiation. Building on the back of the discretized diffusion equations, we built a mathematical model of how these fractones interact with the cells and the associated growth factors produced in order to gain insight into the growth process as a whole. As it is shown in this paper, the complexity of this biological process opens the door to entirely new questions in the field of control theory.MI: Global COE Program Education-and-Research Hub for Mathematics-for-IndustryグローバルCOEプログラム「マス･フォア･インダストリ教育研究拠点

A Mouse Model of β-Thalassemia Shows a Liver-Specific Down-Regulation of Abcc6 Expression

β-Thalassemia and pseudoxanthoma elasticum (PXE) are distinct genetic disorders. Yet, a dystrophic mineralization phenotype similar to PXE has frequently been associated with β-thalassemia or sickle cell anemia patients of Mediterranean descent. These calcifications are clinically and structurally identical to inherited PXE. As we previously excluded the presence of PXE-causing mutations in the ABCC6 gene of β-thalassemia patients with PXE manifestations, we hypothesized that a molecular mechanism independent of gene mutations either altered the ABCC6 gene expression or disrupted the biologic properties of its product in the liver or kidneys, which are the tissues with the highest levels of expression. To test this possibility, we investigated Abcc6 synthesis in the liver and kidneys of a β-thalassemia mouse model (Hbbth3/+). We found a progressive liver-specific down-regulation of the Abcc6 gene expression and protein levels by quantitative PCR, Western blotting, and immunofluorescence. The levels of Abcc6 protein decreased significantly at 6 months of age and stabilized at 10 months and older ages at ∼25% of the wild-type protein levels. We studied the transcriptional regulation of the Abcc6 gene in wild-type and Hbbth3/+ mice, and we identified the erythroid transcription factor NF-E2 as the main cause of the transcriptional down-regulation using transcription factor arrays and chromatin immunoprecipitation. The Hbbth3/+ mice did not develop spontaneous calcification as seen in the Abcc6−/− mice probably because the Abcc6 protein decrease occurred late in life and was probably insufficient to promote mineralization in the Hbbth3/+ mouse C57BL/6J genetic background. Nevertheless, our result suggested that a similar decrease of ABCC6 expression occurs in the liver of β-thalassemia patients and may be responsible for their frequent PXE-like manifestations