GSBS Student Publications

Student Author(s)

Ermelinda Porpiglia

UMMS Affiliation

Department of Pediatrics; Department of Cancer Biology

Date

10-28-2007

Document Type

Article

Medical Subject Headings

Algorithms; Animals; Antigens, CD95; Apoptosis; Cell Differentiation; Cell Separation; Erythrocytes; Erythroid Progenitor Cells; Erythropoiesis; Fas Ligand Protein; Feedback, Biochemical; Fetus; Flow Cytometry; Homeostasis; Liver; Mice; Mice, Inbred C57BL; Signal Transduction

Disciplines

Cell and Developmental Biology | Life Sciences | Medicine and Health Sciences

Abstract

Tissue development is regulated by signaling networks that control developmental rate and determine ultimate tissue mass. Here we present a novel computational algorithm used to identify regulatory feedback and feedforward interactions between progenitors in developing erythroid tissue. The algorithm makes use of dynamic measurements of red cell progenitors between embryonic days 12 and 15 in the mouse. It selects for intercellular interactions that reproduce the erythroid developmental process and endow it with robustness to external perturbations. This analysis predicts that negative autoregulatory interactions arise between early erythroblasts of similar maturation stage. By studying embryos mutant for the death receptor FAS, or for its ligand, FASL, and by measuring the rate of FAS-mediated apoptosis in vivo, we show that FAS and FASL are pivotal negative regulators of fetal erythropoiesis, in the manner predicted by the computational model. We suggest that apoptosis in erythroid development mediates robust homeostasis regulating the number of red blood cells reaching maturity.

Rights and Permissions

Citation: Socolovsky M, Murrell M, Liu Y, Pop R, Porpiglia E, et al. (2007) Negative autoregulation by FAS mediates robust fetal erythropoiesis. PLoS Biol 5(10): e252. doi:10. 1371/journal.pbio.0050252. Link to article on publisher's site

DOI of Published Version

10.1371/journal.pbio.0050252

Comments

Copyright 2007 Socolovsky et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Related Resources

Link to Article in PubMed

Journal Title

PLoS biology

PubMed ID

17896863

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