Neurofibromin 1 regulates early developmental sleep in Drosophila

Durkin, Jaclyn; Poe, Amy R.; Belfer, Samuel J.; Rodríguez, A. Duat; Tang, Sha; Walker, James A.; Kayser, Matthew S.

doi:10.1016/j.nbscr.2023.100101

Cited by 2 publications

(4 citation statements)

References 65 publications

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“…Both dNf1-null flies and Nf1 +/− mice present sexual dimorphism with substantially shorter sleep and sleep fragmentation in males compared to females [56,137], suggesting sex-differential sleep regulation. Interestingly, dNf1 functionally interacts with dAlk in sleep regulation [56,76], as it does in the context of learning [51,52]. Accordingly, genetic inhibition of Alk rescued learning and sleep behaviors in Nf1 +/− -mutant mice [100,138].…”

Section: Sleep Fragmentation and Activity Deficitsmentioning

confidence: 96%

“…Loss of dNf1 results in organismal size reduction [52,71], attenuated associative learning and memory [51,52,72,73], deficits in circadian activities [55,74], behavioral inflexibility manifested as excessive grooming [54,75], aberrant sleep [56,76], and deficits in social behavior [77], summarized in Table 1. The behavioral defects may be consequent of impaired synaptic transmission [78,79], and possibly compromised metabolic homeostasis [80,81].…”

Section: Drosophila Models Of Neurofibromatosis 1 21 the Drosophila N...mentioning

confidence: 99%

“…Each activity cycle is characterized by distinct periods of sleep, defined as any period of immobility lasting for more than 5 min, and shares features of sleep in humans [135,136]. Importantly, dNf1-null flies present significantly disrupted sleep [56,76], as also presented by Nf1 +/− mice [137]. Both dNf1-null flies and Nf1 +/− mice present sexual dimorphism with substantially shorter sleep and sleep fragmentation in males compared to females [56,137], suggesting sex-differential sleep regulation.…”

Section: Sleep Fragmentation and Activity Deficitsmentioning

confidence: 99%

“…Adult dNf1 expression is required for normal sleep in Drosophila across its life span [140], but sleep duration and depth are apparently developmental in origin [76]. Adult flies lacking dNf1 apparently fail to enter deep sleep, presenting sleep fragmentation, reduced arousal threshold, and loss of sleep-dependent reductions in the metabolic rate [141].…”

Section: Sleep Fragmentation and Activity Deficitsmentioning

confidence: 99%

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Drosophila Contributions towards Understanding Neurofibromatosis 1

Atsoniou,

Giannopoulou,

Georganta

et al. 2024

Cells

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Neurofibromatosis 1 (NF1) is a multisymptomatic disorder with highly variable presentations, which include short stature, susceptibility to formation of the characteristic benign tumors known as neurofibromas, intense freckling and skin discoloration, and cognitive deficits, which characterize most children with the condition. Attention deficits and Autism Spectrum manifestations augment the compromised learning presented by most patients, leading to behavioral problems and school failure, while fragmented sleep contributes to chronic fatigue and poor quality of life. Neurofibromin (Nf1) is present ubiquitously during human development and postnatally in most neuronal, oligodendrocyte, and Schwann cells. Evidence largely from animal models including Drosophila suggests that the symptomatic variability may reflect distinct cell-type-specific functions of the protein, which emerge upon its loss, or mutations affecting the different functional domains of the protein. This review summarizes the contributions of Drosophila in modeling multiple NF1 manifestations, addressing hypotheses regarding the cell-type-specific functions of the protein and exploring the molecular pathways affected upon loss of the highly conserved fly homolog dNf1. Collectively, work in this model not only has efficiently and expediently modelled multiple aspects of the condition and increased understanding of its behavioral manifestations, but also has led to pharmaceutical strategies towards their amelioration.

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Section: Sleep Fragmentation and Activity Deficitsmentioning

confidence: 96%

Section: Drosophila Models Of Neurofibromatosis 1 21 the Drosophila N...mentioning

confidence: 99%

Section: Sleep Fragmentation and Activity Deficitsmentioning

confidence: 99%

Section: Sleep Fragmentation and Activity Deficitsmentioning

confidence: 99%

See 2 more Smart Citations

Drosophila Contributions towards Understanding Neurofibromatosis 1

Atsoniou,

Giannopoulou,

Georganta

et al. 2024

Cells

View full text Add to dashboard Cite

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Basic Research Advances and Challenges in NF1 and NF2 Related Pediatric Tumors

Dai,

Zhai,

Huang

2024

Advanced Concepts and Strategies in Central Nervous System Tumors [Working Title]

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This chapter provides a comprehensive overview of the research progress and challenges in neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2), with a focus on pediatric tumors. First, the chapter discusses the genetic and molecular mechanisms of NF1 and NF2, focusing on the key gene mutations that lead to complex pathologies and different clinical manifestations. Then, the chapter discusses the significant impact of advanced genetic, biochemical, and imaging technologies such as high-throughput sequencing and CRISPR/Cas9 gene editing on advancing the research and treatment of these diseases. The chapter also evaluates the advantages of traditional animal models (including mice, zebrafish, and fruit flies) and their application in studying NF1 and NF2, while analyzing the challenges these models face in modeling the genetic heterogeneity of these diseases. Finally, the chapter discusses emerging therapies such as gene therapy, small molecule drugs, and personalized medicine, which offer hope for more effective treatments. The chapter concludes that continued research and interdisciplinary collaboration are essential to translate scientific discoveries into clinical applications, ultimately improving the treatment outcomes of children with NF1- and NF2-related tumors.

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Neurofibromin 1 regulates early developmental sleep in Drosophila

Cited by 2 publications

References 65 publications

Drosophila Contributions towards Understanding Neurofibromatosis 1

Drosophila Contributions towards Understanding Neurofibromatosis 1

Basic Research Advances and Challenges in NF1 and NF2 Related Pediatric Tumors

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