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Dive into the research topics where Annelies Claeys is active.

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Featured researches published by Annelies Claeys.


PLOS Biology | 2010

Robust Target Gene Discovery through Transcriptome Perturbations and Genome-Wide Enhancer Predictions in Drosophila Uncovers a Regulatory Basis for Sensory Specification

Stein Aerts; Xiao-Jiang Quan; Annelies Claeys; Marina Naval Sanchez; Phillip Tate; Jiekun Yan; Bassem A. Hassan

CisTarget X is a novel computational method that accurately predicts Atonal governed regulatory networks in the retina of the fruit fly.


PLOS Biology | 2013

The Drosophila homologue of the amyloid precursor protein is a conserved modulator of Wnt PCP signaling

Alessia Soldano; Zeynep Okray; Pavlína Janovská; Kateřina Tmejová; Elodie Reynaud; Annelies Claeys; Jiekun Yan; Zeynep Kalender Atak; Bart De Strooper; Jean-Maurice Dura; Vítězslav Bryja; Bassem A. Hassan

Wnt Planar Cell Polarity (PCP) signaling is a universal regulator of polarity in epithelial cells, but it regulates axon outgrowth in neurons, suggesting the existence of axonal modulators of Wnt-PCP activity. The Amyloid precursor proteins (APPs) are intensely investigated because of their link to Alzheimers disease (AD). APPs in vivo function in the brain and the mechanisms underlying it remain unclear and controversial. Drosophila possesses a single APP homologue called APP Like, or APPL. APPL is expressed in all neurons throughout development, but has no established function in neuronal development. We therefore investigated the role of Drosophila APPL during brain development. We find that APPL is involved in the development of the Mushroom Body αβ neurons and, in particular, is required cell-autonomously for the β-axons and non-cell autonomously for the α-axons growth. Moreover, we find that APPL is a modulator of the Wnt-PCP pathway required for axonal outgrowth, but not cell polarity. Molecularly, both human APP and fly APPL form complexes with PCP receptors, thus suggesting that APPs are part of the membrane protein complex upstream of PCP signaling. Moreover, we show that APPL regulates PCP pathway activation by modulating the phosphorylation of the Wnt adaptor protein Dishevelled (Dsh) by Abelson kinase (Abl). Taken together our data suggest that APPL is the first example of a modulator of the Wnt-PCP pathway specifically required for axon outgrowth.


Cell | 2016

Post-translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates Neurogenesis

Xiao-Jiang Quan; Liqun Yuan; Luca Tiberi; Annelies Claeys; Natalie De Geest; Jiekun Yan; Rob van der Kant; Wei R. Xie; Tiemo J. Klisch; Joost Shymkowitz; Frederic Rousseau; Mathieu Bollen; Monique Beullens; Huda Y. Zoghbi; Pierre Vanderhaeghen; Bassem A. Hassan

Neurogenesis is initiated by the transient expression of the highly conserved proneural proteins, bHLH transcriptional regulators. Here, we discover a conserved post-translational switch governing the duration of proneural protein activity that is required for proper neuronal development. Phosphorylation of a single Serine at the same position in Scute and Atonal proneural proteins governs the transition from active to inactive forms by regulating DNA binding. The equivalent Neurogenin2 Threonine also regulates DNA binding and proneural activity in the developing mammalian neocortex. Using genome editing in Drosophila, we show that Atonal outlives its mRNA but is inactivated by phosphorylation. Inhibiting the phosphorylation of the conserved proneural Serine causes quantitative changes in expression dynamics and target gene expression resulting in neuronal number and fate defects. Strikingly, even a subtle change from Serine to Threonine appears to shift the duration of Atonal activity in vivo, resulting in neuronal fate defects.


Embo Molecular Medicine | 2015

A novel fragile X syndrome mutation reveals a conserved role for the carboxy‐terminus in FMRP localization and function

Zeynep Okray; Celine de Esch; Hilde Van Esch; Koenraad Devriendt; Annelies Claeys; Jiekun Yan; Jelle Verbeeck; Guy Froyen; Rob Willemsen; Femke M.S. de Vrij; Bassem A. Hassan

Loss of function of the FMR1 gene leads to fragile X syndrome (FXS), the most common form of intellectual disability. The loss of FMR1 function is usually caused by epigenetic silencing of the FMR1 promoter leading to expansion and subsequent methylation of a CGG repeat in the 5′ untranslated region. Very few coding sequence variations have been experimentally characterized and shown to be causal to the disease. Here, we describe a novel FMR1 mutation and reveal an unexpected nuclear export function for the C‐terminus of FMRP. We screened a cohort of patients with typical FXS symptoms who tested negative for CGG repeat expansion in the FMR1 locus. In one patient, we identified a guanine insertion in FMR1 exon 15. This mutation alters the open reading frame creating a short novel C‐terminal sequence, followed by a stop codon. We find that this novel peptide encodes a functional nuclear localization signal (NLS) targeting the patient FMRP to the nucleolus in human cells. We also reveal an evolutionarily conserved nuclear export function associated with the endogenous C‐terminus of FMRP. In vivo analyses in Drosophila demonstrate that a patient‐mimetic mutation alters the localization and function of Dfmrp in neurons, leading to neomorphic neuronal phenotypes.


Developmental Cell | 2016

Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex

Carlos Oliva; Alessia Soldano; Natalia Mora; Natalie De Geest; Annelies Claeys; Maria-Luise Erfurth; Jimena Sierralta; Ariane Ramaekers; Dan Dascenco; Radoslaw K. Ejsmont; Dietmar Schmucker; Natalia Sánchez-Soriano; Bassem A. Hassan

Summary The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body.


eLife | 2017

Evolutionary changes in transcription factor coding sequence quantitatively alter sensory organ development and function

Simon Weinberger; Matthew P. Topping; Jiekun Yan; Annelies Claeys; Natalie De Geest; Duru Ozbay; Talah Hassan; Xiaoli He; Joerg T. Albert; Bassem A. Hassan; Ariane Ramaekers

Animals are characterized by a set of highly conserved developmental regulators. Changes in the cis-regulatory elements of these regulators are thought to constitute the major driver of morphological evolution. However, the role of coding sequence evolution remains unresolved. To address this question, we used the Atonal family of proneural transcription factors as a model. Drosophila atonal coding sequence was endogenously replaced with that of atonal homologues (ATHs) at key phylogenetic positions, non-ATH proneural genes, and the closest homologue to ancestral proneural genes. ATHs and the ancestral-like coding sequences rescued sensory organ fate in atonal mutants, in contrast to non-ATHs. Surprisingly, different ATH factors displayed different levels of proneural activity as reflected by the number and functionality of sense organs. This proneural potency gradient correlated directly with ATH protein stability, including in response to Notch signaling, independently of mRNA levels or codon usage. This establishes a distinct and ancient function for ATHs and demonstrates that coding sequence evolution can underlie quantitative variation in sensory development and function. DOI: http://dx.doi.org/10.7554/eLife.26402.001


Development | 2016

The Drosophila neurogenin tap functionally interacts with the Wnt-PCP pathway to regulate neuronal extension and guidance

Liqun Yuan; Shu Hu; Zeynep Okray; Xi Ren; Natalie De Geest; Annelies Claeys; Jiekun Yan; Eric Bellefroid; Bassem A. Hassan; Xiao-Jiang Quan

The neurogenin (Ngn) transcription factors control early neurogenesis and neurite outgrowth in mammalian cortex. In contrast to their proneural activity, their function in neurite growth is poorly understood. Drosophila has a single predicted Ngn homolog, Tap, of unknown function. Here we show that Tap is not a proneural protein in Drosophila but is required for proper axonal growth and guidance of neurons of the mushroom body, a neuropile required for associative learning and memory. Genetic and expression analyses suggest that Tap inhibits excessive axonal growth by fine regulation of the levels of the Wnt signaling adaptor protein Dishevelled. Summary: Mammalian neurogenins are proneural factors, but the Drosophila homolog Tap is not, instead acting to prevent axonal outgrowth, likely by regulating the planar cell polarity pathway via Dishevelled.


Frontiers in Cellular Neuroscience | 2018

A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury

Marta Koch; Maya Nicolas; Marlen Zschaetzsch; Natalie De Geest; Annelies Claeys; Jiekun Yan; Matthew Morgan; Maria-Luise Erfurth; Matthew Holt; Dietmar Schmucker; Bassem A. Hassan

Injury to the adult central nervous systems (CNS) can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducted a gain-of-function genetic screen in Drosophila to identify strong inducers of axonal growth after injury. We focus on a novel axis the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3′-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism.


bioRxiv | 2018

Altering the temporal regulation of one transcription factor drives sensory trade-offs

Ariane Ramaekers; Simon Weinberger; Annelies Claeys; Martin Kapun; Jiekun Yan; Reinhard Wolf; Thomas Flatt; Erich Buchner; Bassem A. Hassan

Size trade-offs of visual versus olfactory organs is a pervasive feature of animal evolution. Comparing Drosophila species, we find that larger eyes correlate with smaller antennae, where olfactory organs reside, and narrower faces. We demonstrate that this tradeoff arises through differential subdivision of the head primordium into visual versus non-visual fields. Specification of the visual field requires a highly-conserved eye development gene called eyeless in flies and Pax6 in humans. We discover that changes in the temporal regulation of eyeless expression during development is a conserved mechanism for sensory trade-offs within and between Drosophila species. We identify a natural single nucleotide polymorphism in the cis-regulatory region of eyeless that is sufficient to alter its temporal regulation and eye size. Because Pax6 is a conserved regulator of sensory placode subdivision, we propose that alterations in the mutual repression between sensory territories is a conserved mechanism for sensory trade-offs in animals.


PLOS Computational Biology | 2018

A simple computer vision pipeline reveals the effects of isolation on social interaction dynamics in Drosophila

Guangda Liu; Tanmay Nath; Gerit A. Linneweber; Annelies Claeys; Zhengyu Guo; Jin Li; Mercedes Bengochea; Steve De Backer; Barbara Weyn; Manu Sneyders; Hans Nicasy; Peng Yu; Paul Scheunders; Bassem A. Hassan

Isolation profoundly influences social behavior in all animals. In humans, isolation has serious effects on health. Drosophila melanogaster is a powerful model to study small-scale, temporally-transient social behavior. However, longer-term analysis of large groups of flies is hampered by the lack of effective and reliable tools. We built a new imaging arena and improved the existing tracking algorithm to reliably follow a large number of flies simultaneously. Next, based on the automatic classification of touch and graph-based social network analysis, we designed an algorithm to quantify changes in the social network in response to prior social isolation. We observed that isolation significantly and swiftly enhanced individual and local social network parameters depicting near-neighbor relationships. We explored the genome-wide molecular correlates of these behavioral changes and found that whereas behavior changed throughout the six days of isolation, gene expression alterations occurred largely on day one. These changes occurred mostly in metabolic genes, and we verified the metabolic changes by showing an increase of lipid content in isolated flies. In summary, we describe a highly reliable tracking and analysis pipeline for large groups of flies that we use to unravel the behavioral, molecular and physiological impact of isolation on social network dynamics in Drosophila.

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Jiekun Yan

Katholieke Universiteit Leuven

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Zeger Debyser

Katholieke Universiteit Leuven

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Natalie De Geest

Katholieke Universiteit Leuven

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Bart De Strooper

Katholieke Universiteit Leuven

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Bart Nuttin

Katholieke Universiteit Leuven

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Veerle Baekelandt

Katholieke Universiteit Leuven

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Xiao-Jiang Quan

Katholieke Universiteit Leuven

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Kristel Eggermont

Katholieke Universiteit Leuven

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Zeynep Okray

Katholieke Universiteit Leuven

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