Topic: axonal guidance

During brain development, billions of axons navigate over multiple spatial scales to reach specific targets, and so form functional circuits. However, the limited information capacity of the zygotic genome puts a strong constraint on how, and which, axonal routes can be encoded. We propose and validate a mechanism of development that can provide an efficient encoding of this global wiring task. The key principle is that successive mitoses of the neural stem cells induce a hierarchical organization of gene expression patterns in global high dimensional expression space. Provided that mitotic da

The DPYSL5 (Dihydropyrimidinase like 5) gene encodes a cytosolic protein which regulates axonal guidance and neuritic growth. We initially described two missense mutations (p.Glu41Lys, recurrent ; p.Gly47Arg) in DPYSL5 gene in nine individuals presenting intellectual disability and agenesis of the corpus callosum. Interestingly, both variants caused abnormal neuronal development and impaired interaction between DPYSL5 and MAP2 and TUBB3 proteins. Recently, a third de novo variant (p.Glu25Lys) was identified in four individuals with a similar clinical phenotype. Various studies described DPYSL5

Ketosis is a physiological metabolic state, in which fat is the primary energy source (vs glucose), and can be induced through fasting or ketogenic diets (KDs). KDs are rich in lipids and low in carbohydrates, are popular, however, limited literature exists on their safety during pregnancy. Given the essential role of glycolysis in axonal growth dynamics, we hypothesized that KD might disrupt proper axonal guidance during embryonic development, leading to alterations in brain connectivity.Thus, we placed pregnant mice on either a KD or a control diet (CD), starting from gestational day 8.5. KD