Gotfredsen Brown (shockcelery9)

The architecture of renal glomeruli is acquired through intricate and still poorly understood developmental steps. In our study we identify a crucial glomerular morphogenetic event in nephrogenesis that drives the remodeling/separation of the prospective vascular pole (the future entrance of the glomerular arterioles) and the urinary pole (the tubular outflow). We demonstrate that this remodeling is genetically programmed. In fact, in mouse and human, the absence of HNF1B impairs the remodeling/separation of the two poles, leading to trapping and constriction of the tubular outflow inside the glomerulus. This aberration gives rise to obstructive glomerular dilations upon the initiation of primary urine production. In this context, we show that pharmacological decrease of glomerular filtration significantly contains cystic expansion. From a developmental point of view, our study discloses a crucial event on glomerular patterning affecting the "inside-outside" fate of the epithelia in the renal glomerulus.Animal embryogenesis requires a precise coordination between morphogenesis and cell fate specification. During mesoderm induction, mesodermal fate acquisition is tightly coordinated with the morphogenetic process of epithelial-to-mesenchymal transition (EMT). In zebrafish, cells exist transiently in a partial EMT state during mesoderm induction. Here, we show that cells expressing the transcription factor Sox2 are held in the partial EMT state, stopping them from completing the EMT and joining the mesoderm. This is critical for preventing the formation of ectopic neural tissue. The mechanism involves synergy between Sox2 and the mesoderm-inducing canonical Wnt signaling pathway. When Wnt signaling is inhibited in Sox2-expressing cells trapped in the partial EMT, cells exit into the mesodermal territory but form an ectopic spinal cord instead of mesoderm. Our work identifies a critical developmental checkpoint that ensures that morphogenetic movements establishing the mesodermal germ layer are accompanied by robust mesodermal cell fate acquisition.Autism spectrum disorder (ASD) is a neurodevelopmental condition with substantial phenotypic and etiological heterogeneity. Although 10%-20% of ASD cases are attributable to copy number variation (CNV), causative genomic loci and constituent genes remain unclarified. We have developed SNATCNV, a tool that outperforms existing tools, to identify 47 recurrent ASD CNV regions from 19,663 cases and 6,479 controls documented in the AutDB database. Analysis of ASD CNV gene content using FANTOM5 shows that constituent coding genes and long non-coding RNAs have brain-enriched patterns of expression. Notably, such enrichment is not observed for regions identified by using other tools. We also find evidence of sexual dimorphism, one locus uniquely comprising a single lncRNA gene, and correlation of CNVs to distinct clinical and behavioral traits. Finally, we analyze a large dataset for schizophrenia to further demonstrate that SNATCNV is an effective, publicly available tool to define genomic loci and causative genes for multiple CNV-associated conditions.The tumor suppressor p53 regulates multiple metabolic pathways at the cellular level. However, its role in the context of a whole animal response to metabolic stress is poorly understood. Using Drosophila, we show that AMP-activated protein kinase (AMPK)-dependent Dmp53 activation is critical for sensing nutrient stress, maintaining metabolic homeostasis, and extending organismal survival. Under both nutrient deprivation and high-sugar diet, Dmp53 activation in the fat body represses expression of the Drosophila Leptin analog, Unpaired-2 (Upd2), which remotely controls Dilp2 secretion in insulin-producing cells. In starved Dmp53-depleted animals, elevated Upd2 expression in adipose cells and activation of Upd2 receptor Domeless in the brain result in sustained Dilp2 circulating levels and impaired autophagy induction at a systemic level, ther