Female germline expression of OVO transcription factor bridges Drosophila generations.

OVO is required for female germ cell viability but has no known function in the male germline in Drosophila. ovo is autoregulated by two antagonistic isoforms, OVO-A and OVO-B. All ovo- alleles were created as partial revertants of the antimorphic ovoD1 allele.

Diverse somatic Transformer and sex chromosome karyotype pathways regulate gene expression in Drosophila gonad development.

The somatic sex determination gene () is required for the highly sexually dimorphic development of most somatic cells, including those of the gonads. In addition, somatic is required for the germline development even though it is not required for sex determination within germ cells. Germ cell autonomous gene expression is also necessary for their sex determination.

OVO positively regulates essential maternal pathways by binding near the transcriptional start sites in the female germline.

Differentiation of female germline stem cells into a mature oocyte includes the expression of RNAs and proteins that drive early embryonic development in . We have little insight into what activates the expression of these maternal factors. One candidate is the zinc-finger protein OVO.

Muskelin acts as a substrate receptor of the highly regulated CTLH E3 ligase during the maternal-to-zygotic transition.

The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache is replaced with newly made zygotic gene products. We have previously shown that in the deposited RNA-binding proteins ME31B, Cup, and Trailer Hitch (TRAL) are ubiquitylated by the CTLH E3 ligase and cleared. However, the organization and regulation of the CTLH complex remain poorly understood in flies.

OVO Positively Regulates Essential Maternal Pathways by Binding Near the Transcriptional Start Sites in the Female Germline.

Differentiation of female germline stem cells into a mature oocyte includes the expression of RNAs and proteins that drive early embryonic development in . We have little insight into what activates the expression of these maternal factors. One candidate is the zinc-finger protein OVO.

Female germline expression of OVO transcription factor bridges generations.

OVO is required for karyotypically female germ cell viability but has no known function in the male germline in Drosophila. is autoregulated by two antagonistic isoforms, OVO-A and OVO-B. All alleles were created as partial revertants of the antimorphic allele.

Creation of a new X chromosome balancer, ( ), using the CRISPR/Cas9 gene-editing system.

Balancer chromosomes contain multiple inversions that work to suppress crossing over and prevent recovery of most recombinant chromosomes, allowing for alleles to be kept long-term without selection. These balancers are incredible tools, but some alleles within larger inverted segments are still lost to rare double crossover events between the balanced and balancer chromosomes. This study details a new methodology of producing balancer chromosomes using CRISPR/Cas9 gene editing technology to create new inversions within the largest segment of the common X chromosome balancer, We were able to create a new X chromosome balancer, and anticipate that this process can be used to not only create other balancers in but other model organisms as well.

Functional editing of endogenous genes through rapid selection of cell pools (Rapid generation of endogenously tagged genes in Drosophila ovarian somatic sheath cells).

The combination of genome-editing and epitope tagging provides a powerful strategy to study proteins with high affinity and specificity while preserving their physiological expression patterns. However, stably modifying endogenous genes in cells that do not allow for clonal selection has been challenging. Here, we present a simple and fast strategy to generate stable, endogenously tagged alleles in a non-transformed cell culture model.

Heterochromatin Stabilization Requires the Zinc-Finger Protein Small Ovary.

Heterochromatin-mediated repression is essential for controlling the expression of transposons and for coordinated cell type-specific gene regulation. The () locus was identified in a screen for female-sterile mutations in , and mutants show dramatic ovarian morphogenesis defects. We show that the null phenotype is lethal and map the locus to the uncharacterized gene , which encodes a nuclear zinc-finger protein that colocalizes with the essential Heterochromatin Protein 1 (HP1a).

Decoding the 5' nucleotide bias of PIWI-interacting RNAs.

PIWI-interacting RNAs (piRNAs) are at the center of a small RNA-based immune system that defends genomes against the deleterious action of mobile genetic elements (transposons). PiRNAs are highly variable in sequence with extensive targeting potential. Their diversity is restricted by their preference to start with a Uridine (U) at the 5' most position (1U-bias), a bias that remains poorly understood.

Self-Assembly into Nanoparticles Is Essential for Receptor Mediated Uptake of Therapeutic Antisense Oligonucleotides.

Antisense oligonucleotides (ASOs) have the potential to revolutionize medicine due to their ability to manipulate gene function for therapeutic purposes. ASOs are chemically modified and/or incorporated within nanoparticles to enhance their stability and cellular uptake, however, a major challenge is the poor understanding of their uptake mechanisms, which would facilitate improved ASO designs with enhanced activity and reduced toxicity. Here, we study the uptake mechanism of three therapeutically relevant ASOs (peptide-conjugated phosphorodiamidate morpholino (PPMO), 2'Omethyl phosphorothioate (2'OMe), and phosphorothioated tricyclo DNA (tcDNA) that have been optimized to induce exon skipping in models of Duchenne muscular dystrophy (DMD).

Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition.

Introduction: Tau pathology is associated with a number of age-related neurodegenerative disorders. Few treatments have been demonstrated to diminish the impact of tau pathology in mouse models and none are yet effective in humans. Histone deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from cytoplasmic proteins, rather than nuclear histones.

Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology.

Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer's disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons.