Biomedical subjects

Amita Sehgal

Publications and source records attributed to Amita Sehgal.

22 records · Page 2Linked to original sources

PubMed2002

Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest.

Fragile X mental retardation is a prominent genetic disorder caused by the lack of the FMR1 gene product, a known RNA binding protein. Specific physiologic pathways regulated by FMR1 function have yet to be identified. Adult dfmr1 (also called dfxr) mutant flies display arrhythmic circadian activity and have erratic patterns of locomotor activity, whereas overexpression of dFMR1 leads to a lengthened period. dfmr1 mutant males also display reduced courtship activity which appears to result from their inability to maintain courtship interest. Molecular analysis fails to reveal any defects in the expression of clock components; however, the CREB output is affected. Morphological analysis of neurons required for normal circadian behavior reveals subtle abnormalities, suggesting that defects in axonal pathfinding or synapse formation may cause the observed behavioral defects.

Alleles↗

PubMed2002

Signaling components that drive circadian rhythms.

In the past year, knowledge of how information is relayed in the regulation of circadian rhythms has advanced considerably. Experiments using genetic knockout animals suggest that circadian photoreception consists of an integration of multiple signaling pathways. Versatility of clock proteins is seen in terms of their function in the central pacemakers versus the periphery. This versatility also extends to previously identified molecules, such as retinoid receptors, redox factors and mitogen-activated protein kinase, that have newly identified roles in circadian signaling pathways. Advances in circadian research over the past year include the common themes of redundancy and plasticity.

Animals↗

PubMed2002

REV-ving up the clock.

Circadian rhythms are generated by a transcription/translation feedback loop consisting of two limbs, one positive and one negative. The nuclear orphan receptor, REV-ERBalpha, is identified as a molecular link coupling these two limbs.

Animals↗

PubMed2002

Restoration of circadian behavioural rhythms in a period null Drosophila mutant (per01) by mammalian period homologues mPer1 and mPer2.

BACKGROUND: Recent molecular studies suggest that mammals and Drosophila utilize similar components to generate circadian (approximately equal to 24 h) rhythms. The first identified circadian clock gene, the period (per) gene, is indispensable for behavioural rhythms in Drosophila and is represented in mammals by three orthologues, the relative roles of which are not known. In this study, we investigated the functional conservation of per by introducing the mouse mPer1 and mPer2 genes, driven by the Drosophila timeless (tim) promoter, into Drosophila melanogaster. RESULTS: Behavioural assays showed that both mPer constructs restored rhythms in per(01) flies that are otherwise arrhythmic due to a lack of endogenous per protein (PER). However, the rhythms restored by mPer2 were generally stronger and differed in periodicity from those restored by mPer1. In rhythmic transgenic flies, mPER proteins were expressed in lateral neurones and/or many cells in optic lobe. In addition, cell culture experiments indicated that the Drosophila PER partner, TIM, can form a complex with each of these two mammalian proteins. CONCLUSIONS: This study demonstrates that both mPer1 and mPer2 can function as clock components, and has implications for a functional analysis of the different per genes.

Animals↗