Related Experiment Video
Updated: Feb 12, 2026
10:38
Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
Published on: September 27, 2012
23.2K
A Conserved Circadian Function for the Neurofibromatosis 1 Gene
Lei Bai1, Yool Lee1, Cynthia T Hsu1
1Penn Chronobiology, Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cell Reports
|March 29, 2018
Summary
Loss of neurofibromin disrupts circadian rhythms by affecting calcium levels in neurons. This conserved mechanism in flies and mice highlights neurofibromin's role in nervous system signaling.
Area of Science:
- Neuroscience
- Chronobiology
- Molecular Biology
Background:
- Neurofibromatosis 1 (Nf1) protein, neurofibromin, loss in Drosophila disrupts circadian locomotor activity.
- Disruption occurs downstream of central clock function, indicating effects on output pathways.
- Cellular mechanisms underlying neurofibromin's role in circadian rhythms remain unclear.
Purpose of the Study:
- To investigate the cellular mechanisms by which neurofibromin influences circadian locomotor rhythms.
- To identify specific neuronal substrates and signaling pathways affected by neurofibromin.
- To determine if neurofibromin's role in circadian calcium signaling is conserved in mammals.
Main Methods:
- Utilized Drosophila melanogaster as a model organism to study circadian locomotor activity.
- Investigated the effects of Nf1 loss on calcium levels and cycling in peptidergic neurons, particularly in the pars intercerebralis (PI).
- Performed genetic interaction studies with peptide signaling pathways.
- Examined calcium rhythms in mouse astrocytes to assess conservation.
Main Results:
- Neurofibromin modulates calcium levels and cycling in multiple circadian peptidergic neurons in Drosophila.
- Cell-autonomous effects of Nf1 were observed in PI cells secreting DH44, impacting circadian behavior.
- Genetic interactions between Nf1 and peptide signaling pathways were identified.
- Mouse astrocytes exhibit a 24-hour rhythm of calcium levels, which is impaired by the absence of neurofibromin.
Conclusions:
- Neurofibromin plays a crucial role in regulating intracellular calcium rhythms within circadian peptidergic neurons.
- The pars intercerebralis is a key site for neurofibromin's action in the fly circadian system.
- Neurofibromin's involvement in circadian calcium signaling is conserved across species, from insects to mammals.
- These findings reveal a conserved function of neurofibromin in maintaining intracellular signaling rhythms in the nervous system.
Related Concept Videos
02:19Circadian Rhythms and Gene Regulation
4.6K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.6K
01:57What is Conservation Biology?
24.4K
Conservation biology is a scientific field that focuses on the preservation of biodiversity in order to protect ecosystems while meeting the needs of the human population. Humans require properly functioning ecosystems to maintain our supply of natural resources, including food, medicines, and building materials.
24.4K
01:49Conserved Binding Sites
5.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.2K
02:04Conservation of Small Populations
17.4K
Small population sizes put a species at extreme risk of extinction due to a lack of variation, and a consequent decrease in adaptability. This weakens the chances of survival under pressures such as climate change, competition from other species, or new diseases. Large populations are more likely to survive pressures such as these, as such populations are more likely to harbor individuals that have genetic variants that are adaptive under new stresses. Small populations are much less...
17.4K
02:26Conservation of Protein Domains Over Different Proteins
14.7K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
14.7K
02:05Gene Evolution - Fast or Slow?
8.2K
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
8.2K