Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome DOI Creative Commons

Vincenzo Salpietro,

Reza Maroofian, Maha S. Zaki

et al.

The American Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 111(1), P. 200 - 210

Published: Dec. 20, 2023

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 2, which are involved in ribosomal homeostasis. Pathogenic variants were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked GTPBP1. Here, we describe individuals carrying bi-allelic that display identical with characterize the overall spectrum protein (1/2)-related disorders. In this study, 20 from 16 families distinct NDDs syndromic facial features investigated by whole-exome (WES) whole-genome (WGS) sequencing. To assess functional impact identified genetic variants, semi-quantitative PCR, western blot, ribosome profiling assays performed fibroblasts affected individuals. We also effect reducing expression CG2017, ortholog GTPBP1/2, fruit fly Drosophila melanogaster. Individuals presented microcephaly, profound impairment, pathognomonic craniofacial features, ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, brain atrophy part core syndrome. Cell line studies a loss-of-function (LoF) disease-associated but significant abnormalities on profiling. Reduced CG2017 isoforms was associated locomotor impairment Drosophila. conclusion, LoF identical, Mutant knockout flies motor highlighting conserved role for CNS development across species.

Language: Английский

Neural Ensemble Fragmentation in the AnesthetizedDrosophilaBrain DOI Creative Commons
Michael Troup,

Lucy A.L. Tainton-Heap,

Bruno van Swinderen

et al.

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(14), P. 2537 - 2551

Published: March 3, 2023

General anesthetics cause a profound loss of behavioral responsiveness in all animals. In mammals, general anesthesia is induced part by the potentiation endogenous sleep-promoting circuits, although "deep" understood to be more similar coma (Brown et al., 2011). Surgically relevant concentrations anesthetics, such as isoflurane and propofol, have been shown impair neural connectivity across mammalian brain (Mashour Hudetz, 2017; Yang 2021), which presents one explanation why animals become largely unresponsive when exposed these drugs. It remains unclear whether affect dynamics similarly animal brains, or simpler animals, insects, even display levels that could disrupted Here, we used whole-brain calcium imaging behaving female

Language: Английский

Citations

8

Circuits for self-motion estimation and walking control in Drosophila DOI Creative Commons
M Eugenia Chiappe

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 81, P. 102748 - 102748

Published: July 14, 2023

The brain's evolution and operation are inextricably linked to animal movement, critical functions, such as motor control, spatial perception, navigation, rely on precise knowledge of body movement. Such internal estimates self-motion emerge from the integration mechanosensory visual feedback with motor-related signals. Thus, this representation likely depends activity circuits distributed across central nervous system. However, responsible for estimation, exact mechanisms by which motor-sensory coordination occurs within these remain poorly understood. Recent technological advances have positioned Drosophila melanogaster an advantageous model investigating emergence, maintenance, utilization representations during naturalistic walking behaviors. In review, I will illustrate how adult fly is providing insights into fundamental problems computations relevance all animals.

Language: Английский

Citations

7

BIFROST: a method for registering diverse imaging datasets of theDrosophilabrain DOI Creative Commons

Bella E. Brezovec,

Andrew B. Berger,

Yukun A. Hao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 11, 2023

Abstract The heterogeneity of brain imaging methods in neuroscience provides rich data that cannot be captured by a single technique, and our interpretations benefit from approaches enable easy comparison both within across different types. For example, comparing brain-wide neural dynamics experiments aligning such to anatomical resources, as gene expression patterns or connectomes, requires precise alignment common set coordinates. However, this is challenging because registering vivo functional ex reference atlases accommodating differences modality, microscope specification, sample preparation. We overcome these challenges Drosophila building an atlas multiphoton-imaged brains, called the Functional Atlas (FDA). then develop two-step pipeline, BrIdge Registering Over Statistical Templates (BIFROST), for transforming into space importing resources connectomes. Using genetically labeled cell types ground truth, we demonstrate registration with precision less than 10 microns. Overall, BIFROST pipeline datasets fly, experiments. Significance Large-scale have given us new insights activity various sensory behavioral contexts. precisely volumetric images studies has proven challenging, limiting quantitative comparisons Here, address limitation developing BIFROST, robust experimental setups datasets. benchmark labeling fly sub-10 micron precision, specimens laboratories. further accurate between in-vivo volumes ultrastructural enabling direct structure-function future

Language: Английский

Citations

6

BIFROST: A method for registering diverse imaging datasets of the Drosophila brain DOI Creative Commons

Bella E. Brezovec,

Andrew B. Berger,

Yukun A. Hao

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(47)

Published: Nov. 14, 2024

Imaging methods that span both functional measures in living tissue and anatomical fixed have played critical roles advancing our understanding of the brain. However, making direct comparisons between different imaging modalities, particularly spanning tissue, has remained challenging. For example, comparing brain-wide neural dynamics across experiments aligning such data to resources, as gene expression patterns or connectomes, requires precise alignment a common set coordinates. reaching this goal is difficult because registering vivo ex reference atlases accommodating differences modality, microscope specification, sample preparation. We overcome these challenges

Language: Английский

Citations

1

Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome DOI Creative Commons

Vincenzo Salpietro,

Reza Maroofian, Maha S. Zaki

et al.

The American Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 111(1), P. 200 - 210

Published: Dec. 20, 2023

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 2, which are involved in ribosomal homeostasis. Pathogenic variants were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked GTPBP1. Here, we describe individuals carrying bi-allelic that display identical with characterize the overall spectrum protein (1/2)-related disorders. In this study, 20 from 16 families distinct NDDs syndromic facial features investigated by whole-exome (WES) whole-genome (WGS) sequencing. To assess functional impact identified genetic variants, semi-quantitative PCR, western blot, ribosome profiling assays performed fibroblasts affected individuals. We also effect reducing expression CG2017, ortholog GTPBP1/2, fruit fly Drosophila melanogaster. Individuals presented microcephaly, profound impairment, pathognomonic craniofacial features, ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, brain atrophy part core syndrome. Cell line studies a loss-of-function (LoF) disease-associated but significant abnormalities on profiling. Reduced CG2017 isoforms was associated locomotor impairment Drosophila. conclusion, LoF identical, Mutant knockout flies motor highlighting conserved role for CNS development across species.

Language: Английский

Citations

3