title: Developmental lineage priming in Dictyostelium by heterogeneous Ras activation.
abstract: In cell culture, genetically identical cells often exhibit heterogeneous behavior, with only 'lineage primed' cells responding to differentiation inducing signals. It has recently been proposed that such heterogeneity exists during normal embryonic development to allow position independent patterning based on 'salt and pepper' differentiation and sorting out. However, the molecular basis of lineage priming and how it leads to reproducible cell type proportioning are poorly understood. To address this, we employed a novel forward genetic approach in the model organism Dictyostelium discoideum. These studies reveal that the Ras-GTPase regulator gefE is required for normal lineage priming and salt and pepper differentiation. This is because Ras-GTPase activity sets the intrinsic response threshold to lineage specific differentiation signals. Importantly, we show that although gefE expression is uniform, transcription of its target, rasD, is both heterogeneous and dynamic, thus providing a novel mechanism for heterogeneity generation and position-independent differentiation. DOI: http://dx.doi.org/10.7554/eLife.01067.001.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Chattwood
authors.forename: Koki
authors.initials: K
authors.lastname: Nagayama
authors.forename: Parvin
authors.initials: P
authors.lastname: Bolourani
authors.forename: Lauren
authors.initials: L
authors.lastname: Harkin
authors.forename: Marzieh
authors.initials: M
authors.lastname: Kamjoo
authors.forename: Gerald
authors.initials: G
authors.lastname: Weeks
authors.forename: Christopher R L
authors.initials: CR
authors.lastname: Thompson
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D004023:Dictyostelium / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D018631:ras Proteins
keywords: Ras; cell fate choice; heterogeneous; lineage priming; salt and pepper differentiation