Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.

The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a parental sex bias related to Cre expression in sperm or oocytes. Slight differences among Cre driver lines utilizing common transcriptional control elements affect germline recombination rates. Specific target loci demonstrated differential recombination; thus, reporters are not reliable proxies for another locus of interest. Similar principles apply to other recombinase systems and other genetically targeted organisms. We hereby draw attention to the prevalence of germline recombination and provide guidelines to inform future research for the neuroscience and broader molecular genetics communities

Aspirine en prévention de la pré-éclampsie ?

Analyse de : "Villa PM, Kajantie E, Raïkkönen K, et al. Aspirin in the prevention of pre-eclampsia in high-risk women: a randomised placebo-controlled PREDO Trial and a meta-analysis of randomised trials. BJOG 2012;120:64-74." Question clinique : Cette étude de trop faible puissance ne permet pas de confirmer l’efficacité de l’administration d’aspirine dans la prévention de la pré-éclampsie chez des femmes à risque de pré-eclampsie et présentant des anomalies vélocimétriques au doppler des artères utérines. Conclusion Minerva : Quelle est l’efficacité, chez des femmes enceintes à haut risque et présentant des anomalies des artères utérines à l’écho-doppler, de l’administration d’aspirine débutée entre le 84 et le 97ème jour d’aménorrhée en termes de diminution du risque de pré-éclampsie

Apprivoiser les situations complexes

Depuis un an, le département de médecine générale de l’UCLouvain organise un cours pour les assistants généralistes intitulé « L’approche de la promotion de la santé appliquée à la médecine générale. Comment débloquer des situations complexes grâce à l’approche patient partenaire ? ». Derrière les mots, quels sont les enjeux de ce cours

DataSheet1_Loss of Neogenin alters branchial arch development and leads to craniofacial skeletal defects.pdf

The formation of complex structures, such as the craniofacial skeleton, requires precise and intricate two-way signalling between populations of cells of different embryonic origins. For example, the lower jaw, or mandible, arises from cranial neural crest cells (CNCCs) in the mandibular portion of the first branchial arch (mdBA1) of the embryo, and its development is regulated by signals from the ectoderm and cranial mesoderm (CM) within this structure. The molecular mechanisms underlying CM cell influence on CNCC development in the mdBA1 remain poorly defined. Herein we identified the receptor Neogenin as a key regulator of craniofacial development. We found that ablation of Neogenin expression via gene-targeting resulted in several craniofacial skeletal defects, including reduced size of the CNCC-derived mandible. Loss of Neogenin did not affect the formation of the mdBA1 CM core but resulted in altered Bmp4 and Fgf8 expression, increased apoptosis, and reduced osteoblast differentiation in the mdBA1 mesenchyme. Reduced BMP signalling in the mdBA1 of Neogenin mutant embryos was associated with alterations in the gene regulatory network, including decreased expression of transcription factors of the Hand, Msx, and Alx families, which play key roles in the patterning and outgrowth of the mdBA1. Tissue-specific Neogenin loss-of-function studies revealed that Neogenin expression in mesodermal cells contributes to mandible formation. Thus, our results identify Neogenin as a novel regulator of craniofacial skeletal formation and demonstrates it impinges on CNCC development via a non-cell autonomous mechanism.</p