archipelago (ago)/Fbw7 encodes a conserved protein that functions as the substrate-receptor component of a polyubiquitin ligase that suppresses tissue growth in flies and tumorigenesis in vertebrates. Ago/Fbw7 targets multiple proteins for degradation, including the G1-S regulator Cyclin E and the oncoprotein dMyc/c-Myc. Despite prominent roles in growth control, little is known about the signals that regulate Ago/Fbw7 abundance in developing tissues. Here we use the Drosophila eye as a model to identify developmental signals that regulate ago expression. We find that expression of ago mRNA and protein is induced by passage of the morphogenetic furrow (MF) and identify the hedgehog (hh) and Notch (N) pathways as elements of this inductive mechanism. Cells mutant for N pathway components, or hh-defective cells that express reduced levels of the Notch ligand Delta, fail to upregulate ago transcription in the region of the MF; reciprocally, ectopic N activation in eye discs induces expression of ago mRNA. A fragment of the ago promoter that contains consensus binding sites for the N pathway transcription factor Su(H) is bound by Su(H) and confers N-inducibility in cultured cells. The failure to upregulate ago in N pathway mutant cells correlates with accumulation of the SCF-Ago target Cyclin E in the area of the MF, and this is rescued by re-expression of ago. These data suggest a model in which N acts through ago to restrict levels of the pro-mitotic factor Cyclin E. This N-Ago-Cyclin E link represents a significant new cell cycle regulatory mechanism in the developing eye.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005602 | PMC |
| http://dx.doi.org/10.1242/dev.054429 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy.
BMC Ophthalmol
January 2025
Izmir Biomedicine and Genome Center, 35340, Izmir, Türkiye.
Background: Aniridia is a rare panocular disease caused by gene mutation in the PAX6, which is essential for eye development. Aniridia is inherited in an autosomal dominant manner, but its phenotype can vary significantly among individuals with the same mutation. Animal models, such as drosophila, zebrafish, and rodents, have been used to study aniridia through Pax6 deletions.
View Article and Find Full Text PDFDeep conservation complemented by novelty and innovation in the insect eye ground plan.
Proc Natl Acad Sci U S A
January 2025
Department of Cell & Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
A spectacular diversity of forms and features allow species to thrive in different environments, yet some structures remain relatively unchanged. Insect compound eyes are easily recognizable despite dramatic differences in visual abilities across species. It is unknown whether distant insect species use similar or different mechanisms to pattern their eyes or what types of genetic changes produce diversity of form and function.
View Article and Find Full Text PDFMosaicism and intronic variants in RB1 gene revealed by next generation sequencing in a cohort of Spanish retinoblastoma patients.
Exp Eye Res
January 2025
Genetic Diagnosis Unit, Institute for Rare Diseases Research (IIER), Institute of Health Carlos III (ISCIII), Madrid, Spain; CIBER of Rare Diseases (CIBERER), U758. Institute of Health Carlos III (ISCIII), Madrid, Spain.
Constitutional variants in the RB1 gene predispose individuals to the development of Retinoblastoma (RB) and the occurrence of second tumors in adulthood. Detection of causal RB1 gene variants is essential to establish the genetic diagnosis and to performing familial studies and counseling. In our cohort of 579 Spanish RB patients, 15% of cases suspected to have a genetic origin remained negative after traditional Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) of RB1 gene, likely due to the possibility of mosaicism or non-coding variants.
View Article and Find Full Text PDFCell cycle-regulated transcriptional pausing of replication-dependent histone genes.
bioRxiv
December 2024
Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, 27599 USA.
Coordinated expression of replication-dependent (RD) histones genes occurs within the Histone Locus Body (HLB) during S phase, but the molecular steps in transcription that are cell cycle regulated are unknown. We report that RNA Pol II promotes HLB formation and is enriched in the HLB outside of S phase, including G1-arrested cells that do not transcribe RD histone genes. In contrast, the transcription elongation factor Spt6 is enriched in HLBs only during S phase.
View Article and Find Full Text PDFA recurrent neural circuit in Drosophila temporally sharpens visual inputs.
Curr Biol
December 2024
Department of Neurobiology, Stanford University, Stanford, CA 94305, USA. Electronic address:
A critical goal of vision is to detect changes in light intensity, even when these changes are blurred by the spatial resolution of the eye and the motion of the animal. Here, we describe a recurrent neural circuit in Drosophila that compensates for blur and thereby selectively enhances the perceived contrast of moving edges. Using in vivo, two-photon voltage imaging, we measured the temporal response properties of L1 and L2, two cell types that receive direct synaptic input from photoreceptors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!