WUSCHEL (WUS) is a homeodomain transcription factor produced in cells of the niche/organizing center (OC) of shoot apical meristems. WUS specifies stem cell fate and also restricts its own levels by activating a negative regulator, CLAVATA3 (CLV3), in adjacent cells of the central zone (CZ). Here we show that the WUS protein, after being synthesized in cells of the OC, migrates into the CZ, where it activates CLV3 transcription by binding to its promoter elements. Using a computational model, we show that maintenance of the WUS gradient is essential to regulate stem cell number. Migration of a stem cell-inducing transcription factor into adjacent cells to activate a negative regulator, thereby restricting its own accumulation, is a theme that is unique to plant stem cell niches.Supplemental material is available for this article.Received July 5, 2011; revised version accepted September 2, 2011.Cell-cell communication between distinct cell types within stem cell niches is critical for stem cell maintenance in both plants and animals, although they differ in their niche architecture and cell behaviors (Spradling et al. 2008;Rieu and Laux 2009). In animal systems-for example, the Drosophila germline-stem cells make direct contact with the niche cells through adherens junctions and receive local signals that prevent their differentiation (Spradling et al. 2008). Oriented and asymmetric division of stem cells places one of the progeny at a distance by a cell diameter, which no longer can receive signals from the niche and differentiates; thus, precise local cell behaviors regulate stem cell number. Whereas in the shoot apical meristem (SAM) stem cell niche not all stem cells make contact with the niche, they also do not exhibit oriented and asymmetric cell divisions to regulate stem cell numbers. For example, the Arabidopsis SAM stem cell niche is a collection of ;500 cells located at the growing tip of each shoot (Reddy 2008). The CZ of the SAM harbors stem cells. The stem cell progeny that are displaced into the adjacent peripheral zone (PZ) proliferate before differentiating ( Fig. 1A; Reddy 2008). Visually, the SAM stem cell niche is a multilayered structure consisting of three clonally distinct layers of cells, and stem cells are found in each of these layers. The cells in the L1 and the L2 layers divide parallel to the surface to remain as monolayers. The cells in the L3 layer divide in random orientations to form a multilayered structure referred to as the rib meristem (RM) or the organizing center (OC), which provides stem cell-promoting cues (Rieu and Laux 2009).Previous studies have shown that WUSCHEL (WUS), a homeodomain-containing transcription factor, is both necessary and sufficient for stem cell specification (Laux et al. 1996). WUS RNA is found in a few cells of the RM/OC located just beneath the CZ ( Fig. 1A; Mayer et al. 1998). Restriction of WUS transcription to cells of the OC is critical for maintaining a constant number of stem cells, and this is mediated by the CLAVATA (CLV) signaling pathway (...

Shoot apical meristems are stem cell niches that balance proliferation with the incorporation of daughter cells into organ primordia. This balance is maintained by CLAVATA-WUSCHEL feedback signaling between the stem cells at the tip of the meristem and the underlying organizing center. Signals that provide feedback from organ primordia to control the stem cell niche in plants have also been hypothesized, but their identities are unknown. Here we report FASCIATED EAR3 (FEA3), a leucine-rich-repeat receptor that functions in stem cell control and responds to a CLAVATA3/ESR-related (CLE) peptide expressed in organ primordia. We modeled our results to propose a regulatory system that transmits signals from differentiating cells in organ primordia back to the stem cell niche and that appears to function broadly in the plant kingdom. Furthermore, we demonstrate an application of this new signaling feedback, by showing that weak alleles of fea3 enhance hybrid maize yield traits.

The plant stem cell regulator WUSCHEL is shown to repress differentiation-promoting transcription factors. This regulatory network is analyzed with a computational model of the three-dimensional shoot stem cell niche and a combination of genetic perturbation and live imaging.

An epidermis control of plant shoot stem cells can explain the scaling and position of the niche expression domains.

The plant shoot apical meristem holds a stem cell niche from which all aerial organs originate. Using a computational approach we show that a mixture of monomers and heterodimers of the transcription factors WUSCHEL and HAIRY MERISTEM is sufficient to pattern the stem cell niche, and predict that immobile heterodimers form a regulatory “pocket” surrounding the stem cells. The model achieves to reproduce an array of perturbations, including mutants and tissue size modifications. We also show its ability to reproduce the recently observed dynamical shift of the stem cell niche during the development of an axillary meristem. The work integrates recent experimental results to answer the longstanding question of how the asymmetry of expression between the stem cell marker CLAVATA3 and its activator WUSCHEL is achieved, and recent findings of plasticity in the system.

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Background: The transforming growth factor beta is known to have pleiotropic effects, including differentiation, proliferation and apoptosis. However the underlying mechanisms remain poorly understood. The regulation and effect of TGF-β signaling is complex and highly depends on specific protein context. In liver, we have recently showed that the disintegrin and metalloproteinase ADAM12 interacts with TGF-β receptors and modulates their trafficking among membranes, a crucial point in TGF-β signaling and development of fibrosis. The present study aims to better understand how ADAM12 impacts on TGF-β receptors trafficking and TGF-β signaling.

BackgroundRegulation of gene expression plays a pivotal role in cellular functions. However, understanding the dynamics of transcription remains a challenging task. A host of computational approaches have been developed to identify regulatory motifs, mainly based on the recognition of DNA sequences for transcription factor binding sites. Recent integration of additional data from genomic analyses or phylogenetic footprinting has significantly improved these methods.ResultsHere, we propose a different approach based on the compilation of Simple Shared Motifs (SSM), groups of sequences defined by their length and similarity and present in conserved sequences of gene promoters. We developed an original algorithm to search and count SSM in pairs of genes. An exceptional number of SSM is considered as a common regulatory pattern. The SSM approach is applied to a sample set of genes and validated using functional gene-set enrichment analyses. We demonstrate that the SSM approach selects genes that are over-represented in specific biological categories (Ontology and Pathways) and are enriched in co-expressed genes. Finally we show that genes co-expressed in the same tissue or involved in the same biological pathway have increased SSM values.ConclusionsUsing unbiased clustering of genes, Simple Shared Motifs analysis constitutes an original contribution to provide a clearer definition of expression networks.