ORCID Profile
0000-0002-0320-1655
Current Organisations
Sainsbury-Wellcome Centre for Neural Circuits and Behaviour
,
Cairo University
,
National Research Centre
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Publications
A red herring in zebrafish genetics: allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants
Publisher: Cold Spring Harbor Laboratory
Date: 06-08-2021
DOI: 10.1101/2021.08.06.455380
Abstract: In model organisms, RNA sequencing is frequently used to assess the effect of genetic mutations on cellular and developmental processes. Typically, animals heterozygous for a mutation are crossed to produce offspring with different genotypes. Resultant embryos are grouped by genotype to compare homozygous mutant embryos to heterozygous and wild-type siblings. Genes that are differentially expressed between the groups are assumed to reveal insights into the pathways affected by the mutation. Here we show that in zebrafish, differentially expressed genes are often overrepresented on the same chromosome as the mutation due to different levels of expression of alleles from different genetic backgrounds. Using an incross of haplotype-resolved wild-type fish, we found evidence of widespread allele-specific expression, which appears as differential expression when comparing embryos homozygous for a region of the genome to their siblings. When analysing mutant transcriptomes, this means that differentially expressed genes on the same chromosome as a mutation of interest may not be caused by that mutation. Typically, the genomic location of a differentially expressed gene is not considered when interpreting its importance with respect to the phenotype. This could lead to pathways being erroneously implicated or overlooked due to the noise of spurious differentially expressed genes on the same chromosome as the mutation. These observations have implications for the interpretation of RNA-seq experiments involving outbred animals and non-inbred model organisms.
Endogenous interferon γ directly regulates neural precursors in the non-inflammatory brain
Publisher: Society for Neuroscience
Date: 07-07-2010
Allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants
Publisher: eLife Sciences Publications, Ltd
Date: 17-02-2022
DOI: 10.7554/ELIFE.72825
Abstract: In model organisms, RNA-sequencing (RNA-seq) is frequently used to assess the effect of genetic mutations on cellular and developmental processes. Typically, animals heterozygous for a mutation are crossed to produce offspring with different genotypes. Resultant embryos are grouped by genotype to compare homozygous mutant embryos to heterozygous and wild-type siblings. Genes that are differentially expressed between the groups are assumed to reveal insights into the pathways affected by the mutation. Here we show that in zebrafish, differentially expressed genes are often over-represented on the same chromosome as the mutation due to different levels of expression of alleles from different genetic backgrounds. Using an incross of haplotype-resolved wild-type fish, we found evidence of widespread allele-specific expression, which appears as differential expression when comparing embryos homozygous for a region of the genome to their siblings. When analysing mutant transcriptomes, this means that the differential expression of genes on the same chromosome as a mutation of interest may not be caused by that mutation. Typically, the genomic location of a differentially expressed gene is not considered when interpreting its importance with respect to the phenotype. This could lead to pathways being erroneously implicated or overlooked due to the noise of spurious differentially expressed genes on the same chromosome as the mutation. These observations have implications for the interpretation of RNA-seq experiments involving outbred animals and non-inbred model organisms.
Norepinephrine Directly Activates Adult Hippocampal Precursors via β3-Adrenergic Receptors
Publisher: Society for Neuroscience
Date: 17-02-2010
DOI: 10.1523/JNEUROSCI.3780-09.2010
Abstract: Adult hippoc al neurogenesis is a critical form of cellular plasticity that is greatly influenced by neural activity. Among the neurotransmitters that are widely implicated in regulating this process are serotonin and norepinephrine, levels of which are modulated by stress, depression and clinical antidepressants. However, studies to date have failed to address a direct role for either neurotransmitter in regulating hippoc al precursor activity. Here we show that norepinephrine but not serotonin directly activates self-renewing and multipotent neural precursors, including stem cells, from the hippoc us of adult mice. Mechanistically, we provide evidence that β 3 -adrenergic receptors, which are preferentially expressed on a Hes5-expressing precursor population in the subgranular zone (SGZ), mediate this norepinephrine-dependent activation. Moreover, intrahippoc al injection of a selective β 3 -adrenergic receptor agonist in vivo increases the number of proliferating cells in the SGZ. Similarly, systemic injection of the β-adrenergic receptor agonist isoproterenol not only results in enhancement of proliferation in the SGZ but also leads to an increase in the percentage of nestin/glial fibrillary acidic protein double-positive neural precursors in vivo . Finally, using a novel ex vivo “slice-sphere” assay that maintains an intact neurogenic niche, we demonstrate that antidepressants that selectively block the reuptake of norepinephrine, but not serotonin, robustly increase hippoc al precursor activity via β-adrenergic receptors. These findings suggest that the activation of neurogenic precursors and stem cells via β 3 -adrenergic receptors could be a potent mechanism to increase neuronal production, providing a putative target for the development of novel antidepressants.
The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
Publisher: eLife Sciences Publications, Ltd
Date: 07-08-2023
DOI: 10.7554/ELIFE.87521
Abstract: Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist ( dmist ), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na + ,K + -ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a , a Na + ,K + -ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na + levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na + pump function modulates neuronal excitability to maintain normal sleep behaviour.
The Latent Stem Cell Population Is Retained in the Hippocampus of Transgenic Huntington's Disease Mice but Not Wild-Type Mice
Publisher: Public Library of Science (PLoS)
Date: 24-03-2011
The zebrafish mutantdreammistimplicates sodium homeostasis in sleep regulation
Publisher: Cold Spring Harbor Laboratory
Date: 18-11-2020
DOI: 10.1101/2020.11.18.388736
Abstract: Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist ( dmist ), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na + ,K + -ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a , a Na + ,K + -ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na + levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na + pump function modulates neuronal excitability to maintain normal sleep behaviour. Sleep is an essential behavioral state, but the genes that regulate sleep and wake states are still being uncovered. A viral insertion screen in zebrafish identified a novel sleep mutant called dreammist , in which a small, highly-conserved transmembrane protein is disrupted. The discovery of dreammist highlights the importance of a class of small transmembrane-protein modulators of the sodium pump in setting appropriate sleep duration.
Author response: Allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants
Publisher: eLife Sciences Publications, Ltd
Date: 05-01-2022
The adaptor protein Grb2b is an essential modulator for lympho-venous sprout formation in the zebrafish trunk
Publisher: Springer Science and Business Media LLC
Date: 07-03-2021
DOI: 10.1007/S10456-021-09774-W
Abstract: Vegfc/Vegfr3 signaling is critical for lymphangiogenesis, the sprouting of lymphatic vessels. In zebrafish, cells sprouting from the posterior cardinal vein can either form lymphatic precursor cells or contribute to intersegmental vein formation. Both, the Vegfc-dependent differential induction of Prox1a in sprouting cells as well as a Notch-mediated pre-pattern within intersegmental vessels have been associated with the regulation of secondary sprout behavior. However, how exactly a differential lymphatic versus venous sprout cell behavior is achieved is not fully understood. Here, we characterize a zebrafish mutant in the adaptor protein Grb2b, and demonstrate through genetic interaction studies that Grb2b acts within the Vegfr3 pathway. Mutant embryos exhibit phenotypes that are consistent with reduced Vegfr3 signaling outputs prior to the sprouting of endothelial cells from the vein. During secondary sprouting stages, loss of grb2b leads to defective cell behaviors resulting in a loss of parachordal lymphangioblasts, while only partially affecting the number of intersegmental veins. A second GRB2 zebrafish ortholog, grb2a , contributes to the development of lymphatic structures in the meninges and in the head, but not in the trunk. Our results illustrate an essential role of Grb2b in vivo for cell migration to the horizontal myoseptum and for the correct formation of the lymphatic vasculature, while being less critically required in intersegmental vein formation. Thus, there appear to be higher requirements for Grb2b and therefore Vegfr3 downstream signaling levels in lymphatic versus vein precursor-generating sprouts.
Zinc dysregulation in slc30a8 (znt8) mutant zebrafish leads to blindness and disrupts bone mineralisation
Publisher: Cold Spring Harbor Laboratory
Date: 03-09-2020
DOI: 10.1101/2020.09.02.279182
Abstract: Zinc is an essential cofactor for many cellular processes including gene transcription, insulin secretion and retinal function. Excessive free Zn 2+ is highly toxic and consequently intracellular zinc is tightly controlled by a system of transporters, metallothioneins (MTs) and storage vesicles. Here we describe the developmental consequences of a missense allele of zinc efflux transporter slc30a8 ( znt8) in zebrafish. Homozygous slc30a8 hu1798 larvae are virtually blind and develop very little or no bone mineral. We show that zinc is stored in pigmented cells (melanophores) of healthy larvae but in slc30a8 hu1798 mutants it instead accumulates in the bone and brain. Supporting a role for pigment cells in zinc homeostasis, nacre zebrafish, which lack melanophores, also show disrupted zinc homeostasis. The photoreceptors of slc30a8 hu1798 fish are severely depleted while those of nacre fish are enriched with zinc. We propose that developing zebrafish utilise pigmented cells as a zinc storage organ, and that Slc30a8 is required for transport of zinc into these cells and into photoreceptors.
Synthesis of (benzimidazol-2-yl)aniline derivatives as glycogen phosphorylase inhibitors
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.BMC.2016.08.069
Abstract: A series of (benzimidazol-2-yl)-aniline (1) derivatives has been synthesized and evaluated as glycogen phosphorylase (GP) inhibitors. Kinetics studies revealed that compounds displaying a lateral heterocyclic residue with several heteroatoms (series 3 and 5) exhibited modest inhibitory properties with IC
Different synthetic routes to 4-(1H-benzo[d]imidazol-2-yl)aniline
Publisher: Springer Science and Business Media LLC
Date: 18-10-2012
Prolactin Stimulates Precursor Cells in the Adult Mouse Hippocampus
Publisher: Public Library of Science (PLoS)
Date: 04-09-2012
The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
Publisher: eLife Sciences Publications, Ltd
Date: 17-07-2023
Abstract: Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist (dmist), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na+,K+-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na+,K+-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na+ levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na+ pump function modulates neuronal excitability to maintain normal sleep behaviour. Sleep is an essential behavioral state, but the genes that regulate sleep and wake states are still being uncovered. A viral insertion screen in zebrafish identified a novel sleep mutant called dreammist, in which a small, highly-conserved transmembrane protein is disrupted. The discovery of dreammist highlights the importance of a class of small transmembrane-protein modulators of the sodium pump in setting appropriate sleep duration.
A bone to pick with zebrafish
Publisher: Portico
Date: 13-11-2013
The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
Publisher: eLife Sciences Publications, Ltd
Date: 09-05-2023
Abstract: Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist (dmist), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na+,K+-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na+,K+-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na+ levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na+ pump function modulates neuronal excitability to maintain normal sleep behaviour.
Related Organisations
University College London
Location: United Kingdom of Great Britain and Northern Ireland
Sainsbury-Wellcome Centre For Neural Circuits And Behaviour
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Shadia Ahmed Galal.