RESUMEN
In this study, we investigated the role of the transcription factor Six2 in palate development. Six2 was selected using the SysFACE tool to predict genes from the 2p21 locus, a region associated with clefting in humans by GWAS, that are likely to be involved in palatogenesis. We functionally validated the predicted role of Six2 in palatogenesis by showing that 22% of Six2 null embryos develop cleft palate. Six2 contributes to palatogenesis by promoting mesenchymal cell proliferation and regulating bone formation. The clefting phenotype in Six2-/- embryos is similar to Pax9 null embryos, so we examined the functional relationship of these two genes. Mechanistically, SIX2 binds to a PAX9 5' upstream regulatory element and activates PAX9 expression. In addition, we identified a human SIX2 coding variant (p.Gly264Glu) in a proband with cleft palate. We show this missense mutation affects the stability of the SIX2 protein and leads to decreased PAX9 expression. The low penetrance of clefting in the Six2 null mouse combined with the mutation in one patient with cleft palate underscores the potential combinatorial interactions of other genes in clefting. Our study demonstrates that Six2 interacts with the developmental gene regulatory network in the developing palate.
Asunto(s)
Proteínas de Homeodominio/metabolismo , Factor de Transcripción PAX9/genética , Factores de Transcripción/metabolismo , Animales , Fisura del Paladar/embriología , Fisura del Paladar/genética , Anomalías Craneofaciales/embriología , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Genes Homeobox , Proteínas de Homeodominio/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Morfogénesis , Proteínas del Tejido Nervioso/metabolismo , Osteogénesis , Factor de Transcripción PAX9/metabolismo , Factores de Transcripción Paired Box , Hueso Paladar/metabolismo , Transducción de Señal/genética , Factores de Transcripción/genéticaRESUMEN
Food waste and food loss has been a growing concern in the manufacturing industry with a gap between identifying the problem and implementing a solution. The manufacturing process of chicken is largely automated by conveyor belts and machines in which initial application of either peroxyacetic acid (PAA) or sodium hypochlorite (chlorine) solution is utilized to reduce the microbial load and prevent food borne illnesses on the chicken products as they are processed and packaged for distribution. However, during this automated process whole chickens can drop from the manufacturing line and become contaminated leading to the disposal and waste of the product. A solution to reduce food waste was to analyze a reconditioning procedure within the manufacturing process. The study evaluated the aerobic microbial growth on salvaged marinated deli raw whole chickens without giblets (WOGs) from conveyor belt loss reconditioned in either PAA or sodium hypochlorite (chlorine) solution to undropped chicken WOGs. Chicken rinsate and segmented samples were collected from each parameter and tested for microbial growth using Petrifilm aerobic plate count (APC) plates and converting results into log colony forming units (CFU). A difference (P < 0.05) was observed with the reconditioning of the WOGs in PAA (0.71 log10 CFU/mL) compared to the control (1.45 ± 0.26 log10 CFU/mL), for rinses. Of the segmented samples, the trussing strings displayed a significant decrease in APC counts for both chlorine (2.30 ± 0.49 log10 CFU/g) and PAA (2.3 ± 0.49 log10 CFU/g) reconditioning compared to the control (2.72 ± 0.39 log10 CFU/g). Reconditioning of salvaged deli chicken WOGs in chlorine or PAA is comparable to or better than the conventional process for the reduction of APC, it is an effective strategy to reintroduce dropped marinated deli chicken WOGs to the manufacturing line and can reduce food waste at a manufacturing level.