Background: During development, all retinal cell types arise from retinal progenitor cells (RPCs) in a step-wise fashion. Atoh7 and Pou4f2 mark, and function in, two phases of retinal ganglion cell (RGC) genesis; Atoh7 functions in a subpopulation of RPCs to render them competent for the RGC fate, whereas Pou4f2 participates in RGC fate specification and RGC differentiation. Despite extensive research on their roles, the properties of the two phases represented by these two factors have not been well studied, likely due to the retinal cellular heterogeneity.
Results: In this report, we describe two novel knock-in mouse alleles, Atoh7 and Pou4f2 , which labeled retinal cells in the two phases of RGC development by fluorescent proteins. Also, the Atoh7 allele allowed for indirect labeling of RGCs and other cell types upon tamoxifen induction in a dose-dependent manner. Further, these alleles could be used to purify retinal cells in the different phases by fluorescence assisted cell sorting (FACS). Single cell RNA-seq analysis of purified cells from Atoh7 retinas further validated that this allele labeled both transitional/competent RPCs and their progenies including RGCs.
Conclusions: Thus, these two alleles are very useful tools for studying the molecular and genetic mechanisms underlying RGC formation.
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http://dx.doi.org/10.1002/dvdy.233 | DOI Listing |
Sci Adv
January 2025
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the allele of the gene in Hispanic women shortly after a GDM pregnancy.
View Article and Find Full Text PDFCurr Protoc
January 2025
Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Mesothelioma is a lethal cancer of the serosal lining of the body cavities. Risk factors include environmental and genetic factors. Asbestos exposure is considered the principal environmental risk factor, but other carcinogenic mineral fibers, such as erionite, also have a causal role.
View Article and Find Full Text PDFJIMD Rep
January 2025
The Morris Kahn Laboratory of Human Genetics, Faculty of Health Sciences Ben Gurion University Beer-Sheva Israel.
The tightly-regulated spatial and temporal distribution of zinc ion concentrations within cellular compartments is controlled by two groups of Zn transporters: the 14-member ZIP/SLC39 family, facilitating Zn influx into the cytoplasm from the extracellular space or intracellular organelles; and the 10-member ZnT/SLC30 family, mobilizing Zn in the opposite direction. Genetic aberrations in most zinc transporters cause human syndromes. Notably, previous studies demonstrated osteopenia and male-specific cardiac death in mice lacking the ZnT5/ zinc transporter, and suggested association of two homozygous frameshift variants with perinatal mortality in humans, due to hydrops fetalis and hypertrophic cardiomyopathy.
View Article and Find Full Text PDFPLoS Genet
January 2025
Epigenetics & Neurobiology Unit, EMBL Rome, European Molecular Biology Laboratory, Italy.
The reversible glycosylation of nuclear and cytoplasmic proteins (O-GlcNAcylation) is catalyzed by a single enzyme, namely O-GlcNAc transferase (OGT). The mammalian Ogt gene is X-linked, and it is essential for embryonic development and for the viability of proliferating cells. We perturbed OGT's function in vivo by creating a murine allelic series of four single amino acid substitutions, reducing OGT's catalytic activity to a range of degrees.
View Article and Find Full Text PDFTransgenic Res
January 2025
Laboratory of Cell and Developmental Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czech Republic.
Proto-oncogene KRAS, GTPase (KRAS) is one of the most intensively studied oncogenes in cancer research. Although several mouse models allow for regulated expression of mutant KRAS, selective isolation and analysis of transforming or tumor cells that produce the KRAS oncogene remains a challenge. In our study, we present a knock-in model of oncogenic variant KRAS that enables the "activation" of KRAS expression together with production of red fluorescent protein tdTomato.
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