ABSTRACT
Newborn screening is a public health effort that has changed the prognosis of some congenital diseases. Newborn screening programmes differ between countries in which it is organized. Demographic, epidemiological or economic factors play a role in the choice of the screening panel. In the French Community of Belgium, the programme focuses on 13 metabolic and endocrine diseases, hearing loss and hemoglobinopathies (Brussels and Liege). Newborn screening is a complex process that requires the involvement of all stakeholders : parent information, blood sampling or testing, lab analysis, follow-up of the results, initiate adequate care in case of positive test and genetic counselling. Newborn screening programmes will evolve in the next years. New therapeutic and diagnostic methods will make other genetic diseases candidates for screening. Whole genome sequencing may be the next expansion; it will create new opportunities but will pose new ethical dilemmas. We must all prepare now for future challenges.
Subject(s)
Neonatal Screening , Pediatrics , Physician's Role , Female , Hearing Loss , Hearing Tests , Humans , Infant, Newborn , Neonatal Screening/methods , Neonatal Screening/statistics & numerical data , PregnancyABSTRACT
Myogenic differentiation involves myoblast fusion and induction of muscle-specific gene expression, which are both stimulated by pharmacological (LiCl), genetic, or IGF-I-mediated GSK-3ß inactivation. To assess whether stimulation of myogenic differentiation is common to ligand-mediated GSK-3ß inactivation, myoblast fusion and muscle-specific gene expression were investigated in response to Wnt-3a. Moreover, crosstalk between IGF-I/GSK-3ß/NFATc3 and Wnt/GSK-3ß/ß-catenin signaling was assessed. While both Wnt-3a and LiCl promoted myoblast fusion, muscle-specific gene expression was increased by LiCl, but not by Wnt-3a or ß-catenin over-expression. Furthermore, LiCl and IGF-I, but not Wnt-3a, increased NFATc3 transcriptional activity. In contrast, ß-catenin-dependent transcriptional activity was increased by Wnt-3a and LiCl, but not IGF-I. These results for the first time reveal a segregated regulation of myoblast fusion and muscle-specific gene expression following stimulation of myogenic differentiation in response to distinct ligand-specific signaling routes of GSK-3ß inactivation.
Subject(s)
Cell Differentiation/drug effects , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/metabolism , Lithium Chloride/pharmacology , Myoblasts/cytology , Wnt Proteins/metabolism , Animals , Cell Fusion , Cell Line , Enzyme Activation/drug effects , Gene Expression/drug effects , Glycogen Synthase Kinase 3 beta , Insulin-Like Growth Factor I/metabolism , Mice , Muscles/drug effects , Muscles/metabolism , Myoblasts/drug effects , Myoblasts/metabolism , Protein Stability/drug effects , Transcriptional Activation/drug effects , Wnt3 Protein , Wnt3A Protein , beta Catenin/metabolismABSTRACT
Correct Wnt signaling is required for adipogenesis and alterations occur in Type 2 diabetes mellitus (T2DM). Gene expression studies showed that beta-catenin independent Wnt5b was down-regulated in T2DM preadipocytes, while its paralog Wnt5a was unchanged. Our study aimed at defining the expression profile and function of Wnt5a and Wnt5b during adipogenesis by determining their effect on aP2 and PPARgamma expression and assessing the level of beta-catenin translocation in mouse 3T3-L1 preadipocytes. Additionally, we explored the effect on adipogenic capacity by Wnt5b overexpression in combination with stimulation of the beta-catenin dependent or beta-catenin independent Wnt signaling. Expression of Wnt5b was, like Wnt5a, down-regulated upon induction of differentiation and both inhibit beta-catenin dependent Wnt signaling at the initiation of adipogenesis. Wnt5b additionally appears to be a potent enhancer of adipogenic capacity by stimulation of PPARgamma and aP2. Down-regulation of Wnt5b could therefore contribute to decreased adipogenesis observed in T2DM diabetic subjects.
