Molecular networks regulating cell division during Arabidopsis leaf growth

Leaves are the primary organs for photosynthesis and as such have a pivotal role for plant growth and development. Leaf development is a multi-factorial and dynamic process involving many genes that regulate size, shape, and differentiation. The processes that mainly drive leaf development are cell proliferation and cell expansion, and numerous genes have been identified that, when ectopically expressed or down-regulated, increase cell number and/or cell size during leaf growth. Many of the genes regulating cell proliferation are functionally interconnected and can be grouped in regulatory modules. Here, we review our current understanding of six important gene regulatory modules affecting cell proliferation during Arabidopsis leaf growth: DA1-EOD1, GRF-GIF, SWI/SNF, GA-DELLA, KLU, and PEAPOD. Furthermore, we discuss how post-mitotic cell expansion and these six modules regulating cell proliferation make up final leaf size

Comparative transcriptomics enables the identification of functional orthologous genes involved in early leaf growth.

Leaf growth is a complex trait for which many similarities exist in different plant species, suggesting functional conservation of the underlying pathways. However, a global view of orthologous genes involved in leaf growth showing conserved expression in dicots and monocots is currently missing. Here we present a genome-wide comparative transcriptomics analysis between Arabidopsis and maize, identifying conserved biological processes and gene functions active during leaf growth. Despite the orthology complexity between these distantly related plants, 926 orthologous gene groups including 2,829 Arabidopsis and 2,974 maize genes with similar expression during leaf growth were found, indicating conservation of the underlying molecular networks. We found 65% of these genes involved in one-to-one orthology, whereas only 28.7% of the groups with divergent expression had one-to-one orthology. Within the pool of genes with conserved expression, 19 transcription factor families were identified, demonstrating expression conservation of regulators active during leaf growth. Additionally, 25 Arabidopsis and 25 maize putative targets of the TCP TFs with conserved expression were determined based on the presence of enriched transcription factor binding sites. Based on large-scale phenotypic data, we observed that genes with conserved expression have a higher probability to be involved in leaf growth and that leaf-related phenotypes are more frequently present for genes having orthologs between dicots and monocots than clade-specific genes. This study shows the power of integrating transcriptomics with orthology data to identify or select candidates for functional studies during leaf development in flowering plants

Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53.

Nutlin-3 activates the p53 pathway and suppresses tumor growth in this model system of chemoresistant neuroblastoma, provided that wild-type p53 is present

The Mitochondrial DNA (mtDNA)-Associated Protein SWIB5 Influences mtDNA Architecture and Homologous Recombination

In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared to their animal counterparts and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana. Gain- and loss-of-function mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture and homologous recombination at specific intermediate-sized repeats both under normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family members suggests a link between organellar genome maintenance and cell proliferation. Taken together, our work presents a protein family that influences mtDNA architecture and homologous recombination in plants and suggests a link between organelle functioning and plant development