Publications by authors named "P Callaerts"

94 Publications

Glial and Neuronal Neuroglian, Semaphorin-1a and Plexin A Regulate Morphological and Functional Differentiation of Insulin-Producing Cells.

Front Endocrinol (Lausanne) 2021 1;12:600251. Epub 2021 Jul 1.

Laboratory of Behavioral and Developmental Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.

The insulin-producing cells (IPCs), a group of 14 neurons in the brain, regulate numerous processes, including energy homeostasis, lifespan, stress response, fecundity, and various behaviors, such as foraging and sleep. Despite their importance, little is known about the development and the factors that regulate morphological and functional differentiation of IPCs. In this study, we describe the use of a new transgenic reporter to characterize the role of the L1-CAM homolog Neuroglian (Nrg), and the transmembrane Semaphorin-1a (Sema-1a) and its receptor Plexin A (PlexA) in the differentiation of the insulin-producing neurons. Loss of Nrg results in defasciculation and abnormal neurite branching, including ectopic neurites in the IPC neurons. Cell-type specific RNAi knockdown experiments reveal that Nrg, Sema-1a and PlexA are required in IPCs and glia to control normal morphological differentiation of IPCs albeit with a stronger contribution of Nrg and Sema-1a in glia and of PlexA in the IPCs. These observations provide new insights into the development of the IPC neurons and identify a novel role for Sema-1a in glia. In addition, we show that Nrg, Sema-1a and PlexA in glia and IPCs not only regulate morphological but also functional differentiation of the IPCs and that the functional deficits are likely independent of the morphological phenotypes. The requirements of , , and in IPC development and the expression of their vertebrate counterparts in the hypothalamic-pituitary axis, suggest that these functions may be evolutionarily conserved in the establishment of vertebrate endocrine systems.
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http://dx.doi.org/10.3389/fendo.2021.600251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281472PMC
July 2021

Identification and bioinformatic analysis of neprilysin and neprilysin-like metalloendopeptidases in .

MicroPubl Biol 2021 Jun 23;2021. Epub 2021 Jun 23.

FlyBase, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, U.K.

The neprilysin (M13) family of metalloendopeptidases comprises highly conserved ectoenzymes that cleave and thereby inactivate many physiologically relevant peptides in the extracellular space. Impaired neprilysin activity is associated with numerous human diseases. Here, we present a comprehensive list and classification of M13 family members in . Seven () genes encode active peptidases, while 21 () genes encode proteins predicted to be catalytically inactive. RNAseq data demonstrate that all 28 genes are expressed during development, often in a tissue-specific pattern. Most Nep proteins possess a transmembrane domain, whereas almost all Nepl proteins are predicted to be secreted.
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http://dx.doi.org/10.17912/micropub.biology.000410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223033PMC
June 2021

Evolutionary novelty in the apoptotic pathway of aphids.

Proc Natl Acad Sci U S A 2020 12 7;117(51):32545-32556. Epub 2020 Dec 7.

UMR0203, Biologie Fonctionnelle, Insectes et Interactions (BF2i), Institut National des Sciences Appliquées Lyon (INSA Lyon), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), University of Lyon (Univ Lyon), F-69621 Villeurbanne, France;

Apoptosis, a conserved form of programmed cell death, shows interspecies differences that may reflect evolutionary diversification and adaptation, a notion that remains largely untested. Among insects, the most speciose animal group, the apoptotic pathway has only been fully characterized in , and apoptosis-related proteins have been studied in a few other dipteran and lepidopteran species. Here, we studied the apoptotic pathway in the aphid , an insect pest belonging to the Hemiptera, an earlier-diverging and distantly related order. We combined phylogenetic analyses and conserved domain identification to annotate the apoptotic pathway in and found low caspase diversity and a large expansion of its inhibitory part, with 28 inhibitors of apoptosis (IAPs). We analyzed the spatiotemporal expression of a selected set of pea aphid IAPs and showed that they are differentially expressed in different life stages and tissues, suggesting functional diversification. Five IAPs are specifically induced in bacteriocytes, the specialized cells housing symbiotic bacteria, during their cell death. We demonstrated the antiapoptotic role of these five IAPs using heterologous expression in a tractable in vivo model, the developing eye. Interestingly, IAPs with the strongest antiapoptotic potential contain two BIR and two RING domains, a domain association that has not been observed in any other species. We finally analyzed all available aphid genomes and found that they all show large IAP expansion, with new combinations of protein domains, suggestive of evolutionarily novel aphid-specific functions.
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http://dx.doi.org/10.1073/pnas.2013847117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768685PMC
December 2020

Ancestral regulatory mechanisms specify conserved midbrain circuitry in arthropods and vertebrates.

Proc Natl Acad Sci U S A 2020 08 3;117(32):19544-19555. Epub 2020 Aug 3.

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 9RT, United Kingdom;

Corresponding attributes of neural development and function suggest arthropod and vertebrate brains may have an evolutionarily conserved organization. However, the underlying mechanisms have remained elusive. Here, we identify a gene regulatory and character identity network defining the deutocerebral-tritocerebral boundary (DTB) in This network comprises genes homologous to those directing midbrain-hindbrain boundary (MHB) formation in vertebrates and their closest chordate relatives. Genetic tracing reveals that the embryonic DTB gives rise to adult midbrain circuits that in flies control auditory and vestibular information processing and motor coordination, as do MHB-derived circuits in vertebrates. DTB-specific gene expression and function are directed by -regulatory elements of developmental control genes that include homologs of mammalian and DTB-specific -regulatory elements correspond to regulatory sequences of human , and that direct MHB-specific expression in the embryonic mouse brain. We show that -regulatory elements and the gene networks they regulate direct the formation and function of midbrain circuits for balance and motor coordination in insects and mammals. Regulatory mechanisms mediating the genetic specification of cephalic neural circuits in arthropods correspond to those in chordates, thereby implying their origin before the divergence of deuterostomes and ecdysozoans.
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http://dx.doi.org/10.1073/pnas.1918797117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431035PMC
August 2020

Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits.

Cell 2020 03;180(6):1178-1197.e20

Department of Fundamental Neurosciences, University of Lausanne, Lausanne 1005, Switzerland; University of Rome Tor Vergata, Department of Biomedicine and Prevention, Rome 00133, Italy. Electronic address:

Social impairment is frequently associated with mitochondrial dysfunction and altered neurotransmission. Although mitochondrial function is crucial for brain homeostasis, it remains unknown whether mitochondrial disruption contributes to social behavioral deficits. Here, we show that Drosophila mutants in the homolog of the human CYFIP1, a gene linked to autism and schizophrenia, exhibit mitochondrial hyperactivity and altered group behavior. We identify the regulation of GABA availability by mitochondrial activity as a biologically relevant mechanism and demonstrate its contribution to social behavior. Specifically, increased mitochondrial activity causes gamma aminobutyric acid (GABA) sequestration in the mitochondria, reducing GABAergic signaling and resulting in social deficits. Pharmacological and genetic manipulation of mitochondrial activity or GABA signaling corrects the observed abnormalities. We identify Aralar as the mitochondrial transporter that sequesters GABA upon increased mitochondrial activity. This study increases our understanding of how mitochondria modulate neuronal homeostasis and social behavior under physiopathological conditions.
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http://dx.doi.org/10.1016/j.cell.2020.02.044DOI Listing
March 2020
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