RUNX genes find a niche in stem cell biology.

The RUNX family of transcriptional regulators are well conserved throughout the animal kingdom, from the simple nematode worm Caenorhabditis elegans to vertebrates. Interest in the RUNX genes emerged principally as a result of the finding that chromosomal translocations disrupting RUNX protein function are observed in a large number of patients suffering with acute myeloid leukemia (AML). In the 20 years that RUNX genes have been under investigation, they have emerged as central players in the control of developmental decisions between proliferation and differentiation in a wide variety of biological situations. This review focuses on recent data highlighting the roles of RUNX genes in stem cells and illustrates the diversity of processes in which the RUNX proteins play a critical role. In particular, we focus on the role of RUNX1 in hematopoietic stem cells (HSCs) and hair follicle stem cells (HFSCs) and the importance of the solo C. elegans RUNX factor rnt-1 in stem cell proliferation in the worm. Observations in a variety of stem cell systems have developed to the point where useful comparisons can be made, from which guiding principles may emerge

Identification of cis-regulatory elements from the C. elegans T-box gene mab-9 reveals a novel role for mab-9 in hypodermal function.

We have identified Conserved Non-coding Elements (CNEs) in the regulatory region of Caenorhabditis elegans and Caenorhabditis briggsae mab-9, a T-box gene known to be important for cell fate specification in the developing C. elegans hindgut. Two adjacent CNEs (a region 78 bp in length) are both necessary and sufficient to drive reporter gene expression in posterior hypodermal cells. The failure of a genomic mab-9::gfp construct lacking this region to express in posterior hypodermis correlates with the inability of this construct to completely rescue the mab-9 mutant phenotype. Transgenic males carrying this construct in a mab-9 mutant background exhibit tail abnormalities including morphogenetic defects, altered tail autofluorescence and abnormal lectin-binding properties. Hermaphrodites display reduced susceptibility to the C. elegans pathogen Microbacterium nematophilum. This comparative genomics approach has therefore revealed a previously unknown role for mab-9 in hypodermal function and we suggest that MAB-9 is required for the secretion and/or modification of posterior cuticle

The UNC-4 homeobox protein represses mab-9 expression in DA motor neurons in Caenorhabditis elegans.

The T-box transcription factor mab-9 has been shown to be required for the correct fate of the male-specific blast cells B and F, normal posterior hypodermal morphogenesis, and for the correct axon migration of motor neurons that project circumferential commissures to dorsal muscles. In this study, an RNAi screen designed to identify upstream transcriptional regulators of mab-9 showed that silencing of unc-4 (encoding a paired-class homeodomain protein) increases mab-9::gfp expression in the nervous system, specifically in posterior DA motor neurons. Over-expression of unc-4 from a heat-shock promoter has the opposite effect, causing repression of mab-9 in various cells. We find that mab-9 expression in unc-37 mutants is also elevated in DA motor neurons, consistent with known roles for UNC-37 as a co-repressor with UNC-4. These results identify mab-9 as a novel target of the UNC-4/UNC-37 repressor complex in motor neurons, and suggest that mis-expression of mab-9 may contribute to the neuronal wiring defects in unc-4 and unc-37 mutants

Förväntningar på megaprojekt : Kommunala strategier i Norrköping för Ostlänken

När staten rullar ut sin matta av infrastruktursatsningar ställer det höga krav på de angörande kommunerna. Men det skapar också förväntningar som utgör en helt ny och omfattande grund för planering. I Norrköping förbereds nu för Ostlänken vilket innebär djupgående effekter på såväl organisation som processer, även om många ideal för samtidens stadsutveckling känns igen. Brita Hermelin, Fredrik Wallin och Sara Gustafsson beskriver projektet och de lokala planeringsförberedelserna