Gliogenesis Depends on glide/gcm through Asymmetric Division of Neuroglioblasts

AbstractSome neurons and glial cells originate from neuroblasts and glioblasts, stem cells that delaminate from the ectoderm of developing fly embryos. A second class of glial cells and neurons differentiates from multipotent precursors, the neuroglioblasts. The differentiation of both glial cell types depends on glial cell deficient/glial cell missing (glide/gcm). Although it has been shown that this transcription factor promotes gliogenesis at the expense of neurogenesis, the cellular mechanisms underlying this fate choice are poorly understood. Using loss and gain of function glide/gcm mutations here we show that the cell fate choice takes place in the neuroglioblast, which divides and produces a glioblast and a neuroblast. Such choice requires the asymmetric distribution of glide/gcm RNA, which accumulates preferentially on one side of the neuroglioblast and is inherited by one cell, the presumptive glioblast. Interestingly, glial cells can differentiate from cells that delaminate as neuroglioblasts or they can arise from cells that start expressing glide/gcm several hours after delamination of a neuroblast. Altogether, these findings identify a novel type of asymmetric cell division and disclose the lineage relationships between glia and neurons. They also reveal the mode of action of the glide/gcm promoting factor

Etude du rôle des gènes de la famille glide/gcm dans les mécanismes de différenciation gliale chez Drosophila melanogaster

STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Glide2, a second glial promoting factor in Drosophila melanogaster

The fly glial cell deficient/glial cell missing (glide/gcm) gene codes for a transcription factor that induces gliogenesis. Lack of its product eliminates lateral glial cells in the embryonic nervous system. Here we identify a second gene, glide2, that is homologous to glide/gcm in the binding domain and that is also necessary and sufficient to promote glial differentiation. glide2 codes for a transcription factor that displays a weaker and delayed expression compared with glide/gcm. The two genes, which are located 27 kb apart and share cis-regulatory elements, are able to auto- and cross-regulate, indicating that they form a gene complex. Finally, we show that lack of both products eliminates all lateral glial cells, which means that the two genes contain all the fly lateral glial promoting activity

Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model

The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer-specific matrix, and high TNC expression is linked to poor prognosis in several cancers. To provide a comprehensive understanding of TNC's functions in cancer, we established an immune-competent transgenic mouse model of pancreatic β-cell carcinogenesis with varying levels of TNC expression and compared stochastic neuroendocrine tumor formation in abundance or absence of TNC. We show that TNC promotes tumor cell survival, the angiogenic switch, more and leaky vessels, carcinoma progression, and lung micrometastasis. TNC downregulates Dickkopf-1 (DKK1) promoter activity through the blocking of actin stress fiber formation, activates Wnt signaling, and induces Wnt target genes in tumor and endothelial cells. Our results implicate DKK1 downregulation as an important mechanism underlying TNC-enhanced tumor progression through the provision of a proangiogenic tumor microenvironment