Pleiotropic Functions of FoxN1: Regulating Different Target Genes during Embryogenesis and Nymph Molting in the Brown Planthopper.

FoxN1 gene belongs to the forkhead box gene family that comprises a diverse group of "winged helix" transcription factors that have been implicated in a variety of biochemical and cellular processes. In the brown planthopper (BPH), FoxN1 is highly expressed in the ovaries and newly laid eggs, where it acted as an indispensable gene through its molecular targets to regulate early embryonic development. Moreover, the results of the RNAi experiments indicated that Nilaparvata lugens FoxN1 (NlFoxN1) exhibited pleiotropism: they not only affected the embryogenesis, but also played an important role in molting. RNA-seq and RNAi were further used to reveal potential target genes of NlFoxN1 in different stages. In the eggs, ten downregulated genes were defined as potential target genes of NlFoxN1 because of the similar expression patterns and functions with NlFoxN1. Knockdown of NlFoxN1 or any of these genes prevented the development of the eggs, resulting in a zero hatchability. In the nymphs, NlFoxN1 regulated the expression of a keratin gene, type I cytoskeletal keratin 9 (NlKrt9), to participate in the formation of an intermediate filament framework. Depletion of NlFoxN1 or NlKrt9 in nymphs, BPHs failed to shed their old cuticle during nymph-to-nymph or nymph-to-adult molting and the mortality was almost 100%. Altogether, the pleiotropic roles of NlFoxN1 during embryogenesis and nymph molting were supported by the ability to coordinate the temporal and spatial gene expression of their target genes.

A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair.

BACKGROUND: Woolly hair (WH) is a hair abnormality that is primarily characterised by tightly curled hair with abnormal growth. METHODS: In two unrelated consanguineous Pakistani families with non-syndromic autosomal recessive (AR) WH, homozygosity mapping and linkage analysis identified a locus within 17q21.1-q22, which contains the type I keratin gene cluster. A DNA sample from an affected individual from each family underwent exome sequencing. RESULTS: A homozygous missense variant c.950T>C (p.(Leu317Pro)) within KRT25 segregated with ARWH in both families, and has a combined maximum two-point LOD score of 7.9 at Ï´=0. The KRT25 variant is predicted to result in disruption of the second α-helical rod domain and the entire protein structure, thus possibly interfering with heterodimerisation of K25 with type II keratins within the inner root sheath (IRS) of the hair follicle and the medulla of the hair shaft. CONCLUSIONS: Our findings implicate a novel gene involved in human hair abnormality, and are consistent with the curled, fragile hair found in mice with Krt25 mutations, and further support the role of IRS-specific type I keratins in hair follicle development and maintenance of hair texture.

Investigating the role of keratin proteins and microbial associations in hereditary and pathogenic alopecia.

The purpose of this research was to identify the role of keratin proteins in causing inherited as well as pathogenic alopecia, pinpoint deleterious SNPs, and predict structural changes affecting protein-protein interactions in hair disorders. To elucidate the role of keratin proteins and genetic mutations in alopecia by analyzing protein structures through bioinformatics and identifying a mutation in the LPAR6 gene. It sought to identify the microorganisms linked to alopecia and conducted a comprehensive bioinformatics analysis of proteins with unknown experimental structures and molecular simulation analysis. The study identified a genetic mutation (c.188 A > T, p.Asp63Val) in the LPAR6 gene associated with hereditary hair loss. Pathogenic alopecia was identified to be associated with S. aureus and two ic keratinophilic fungi namely M. canis, and T. violaceum. Additionally, among 14 proteins lacking prior structural information, four proteins namely Keratin, type II cuticular Hb3 (KR1), Keratin, type II cuticular Hb6 (KR2), Keratin, type II cytoskeletal 74 (KR3) and Keratin, type II cuticular Hb1 (KR4) exhibited common 'K-head' and 'F' domains. Docking analysis revealed five distinct binding sites (C1-C5) for each protein. The 'K-head' displayed the highest predicted binding affinities with Vina scores of -5.6 for KR2 and - 4.7 for KR4 whereas the 'F' domain showed Vina scores of -6.0 for KR3 and - 5.7 for KR2. This research underscores the crucial role of keratin proteins in both hereditary and pathogenic alopecia, emphasizing their significance for future investigations.