Genetic screens are used in to identify genes key in the regulation of organismal development and growth. These screens have defined signalling pathways necessary for tissue and organismal development, which are evolutionarily conserved across species, including . Here, we have used an FLP/FRT mosaic system to screen for conditional regulators of cell growth and cell division in the eye. The conditional nature of this screen utilizes a block in the apoptotic pathway to prohibit the mosaic mutant cells from dying via apoptosis. From this screen, we identified two different mutants that mapped to the Hedgehog signalling pathway. Previously, we described a novel mutation and here we add to the understanding of disrupting the Hh pathway with a novel allele of . Both of these Hh components are negative regulators of the pathway, yet they depict mutant differences in the type of overgrowth created. mutations lead to overgrowth consisting of almost entirely wild-type tissue (non-autonomous overgrowth), while the mutation results in tissue that is overgrown in both the mutant and wild-type clones (both autonomous and non-autonomous). These differences in tissue overgrowth are consistent in the eye and wing. The observed difference is correlated with different deregulation patterns of pMad, the downstream effector of DPP signalling. This finding provides insight into pathway-specific differences that help to better understand intricacies of developmental processes and human diseases that result from deregulated Hedgehog signalling, such as basal cell carcinoma.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045829 | PMC |
http://dx.doi.org/10.1080/19336934.2022.2062991 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Shenzhen Key Laboratory of Biomolecular Assembling and Regulation, Department of Neuroscience, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
Ankyrin Repeat Domain-containing Protein 11 () is a causative gene for KBG syndrome, a significant risk factor for Cornelia de Lange syndrome (CdLS), and a highly confident autism spectrum disorder gene. Mutations of lead to developmental abnormalities in multiple organs/tissues including the brain, craniofacial and skeletal bones, and tooth structures with unknown mechanism(s). Here, we find that ANKRD11, via a short peptide fragment in its N-terminal region, binds to the cohesin complex with a high affinity, implicating why mutation can cause CdLS.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036 Tamil Nadu, India.
Interactions between proteins and RNAs are essential for the proper functioning of cells, and mutations in these molecules may lead to diseases. These protein mutations alter the strength of interactions between the protein and RNA, generally described as binding affinity (Δ). Hence, the affinity change upon mutation (ΔΔ) is an important parameter for understanding the effect of mutations in protein-RNA complexes.
View Article and Find Full Text PDFCell Death Differ
January 2025
Laboratory for Experimental Leukemia and Lymphoma Research (ELLF), LMU University Hospital, Munich, Germany.
The cell death receptor FAS and its ligand (FASLG) play crucial roles in the selection of B cells during the germinal center (GC) reaction. Failure to eliminate potentially harmful B cells via FAS can lead to lymphoproliferation and the development of B cell malignancies. The classic form of follicular lymphoma (FL) is a prototypic GC-derived B cell malignancy, characterized by the t(14;18)(q32;q21)IGH::BCL2 translocation and overexpression of antiapoptotic BCL2.
View Article and Find Full Text PDFNPJ Antimicrob Resist
November 2024
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Apart from horizontal gene transfer and sequence-altering mutational events, antibiotic resistance can emerge due to the formation of tandem repeats of genomic regions. This phenomenon, also known as gene amplification, has been implicated in antibiotic resistance in both laboratory and clinical scenarios, where the evolution of resistance via amplifications can affect treatment efficacy. Antibiotic resistance mediated by gene amplifications is unstable and consequently can be difficult to detect, due to amplification loss in the absence of the selective pressure of the antibiotic.
View Article and Find Full Text PDFSci Rep
January 2025
Institute of Molecular Biology and Pathology, National Research Council, 00185, Rome, Italy.
Mutations of the MECP2 gene lead to Rett syndrome (RTT), a rare developmental disease causing severe intellectual and physical disability. How the loss or defective function of MeCP2 mediates RTT is still poorly understood. MeCP2 is a global gene expression regulator, acting at transcriptional and post-transcriptional levels.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!