Chi-Yun Pai, Tung-Sheng Kuo, Thomas J. Jaw, Estee Kurant, Cheng-Tse Chen, Dmitri A. Bessarab, Adi Salzberg, and Y. Henry Sun Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan, Republic China, Life Science, National Yat-Sen University, Kaohsiung, Taiwan; Genetics, Yang-Ming Shipai, Taipei, Unit Rappaport Faculty Medicine, Technion-Israel Technology, Haifa 31096, Israel

ABSTRACT The homeotic genes of the bithorax complex are required, among other things, for establishing patterns sensory organs in embryonic peripheral nervous system (PNS). However, molecular mechanisms by which these affect pattern formation PNS not understood and that function this pathway characterized. Here we report phenotypic analysis one such gene, homothorax (hth; also named dorsotonals). Mutations hth gene seem to alter identity abdominal chordotonal neurons, depend on Abd-A their...

Highlights•Santa-maria is a Drosophila glial phagocytic receptor for apoptotic neurons•Santa-maria acts upstream to SIMU and Draper in the phagocytosis of binds cells vivo vitroSummaryThe elimination superfluous neurons via apoptosis subsequent crucial development central nervous system (CNS). In Drosophila, two receptors, six-microns-under (SIMU) Draper, mediate during embryogenesis. However, simu;draper double-mutant embryos, some are still engulfed by glia, suggesting involvement...

Glial phagocytosis is critical for the development and maintenance of CNS in vertebrates flies relies on function phagocytic receptors to remove apoptotic cells debris. ability declines with age, which correlates neuronal dysfunction, suggesting that increased glial may prevent neurodegeneration. Contradicting this hypothesis, we provide experimental evidence showing an elevated expression Six-Microns-Under (SIMU) Draper (Drpr) adult Drosophila glia leads a loss both dopaminergic GABAergic...

Clearance of apoptotic cells by phagocytic neighbors is crucial for normal development multicellular organisms. However, how phagocytes discriminate between healthy and dying remains poorly understood. We focus on glial phagocytosis neurons during the Drosophila central nervous system. identified phosphatidylserine (PS) as a ligand receptor Six Microns Under (SIMU) report that PS alone not sufficient engulfment. Our data reveal that, additionally to exposure, caspase activity required...

Abstract Development of the central nervous system involves elimination superfluous neurons through apoptosis and subsequent phagocytosis. In Drosophila , this occurs mainly during three developmental stages: embryogenesis, metamorphosis emerging adult. Two transmembrane glial phagocytic receptors, SIMU (homolog mammalian Stabilin‐2) Draper MEGF10 Jedi), mediate phagocytosis apoptotic embryogenesis. However, less is known about removal later stages development. Here we show that...

Glial phagocytosis of superfluous neurons and damaged or aberrant neuronal material is crucial for normal development maintenance the CNS. However, molecular mechanisms underlying relationship between death glial are poorly understood. We describe a novel mechanism that able to synchronize cell dying in Drosophila embryonic This involves c-Jun N-terminal kinase (JNK) signaling, which required developmental apoptosis specific during embryogenesis. demonstrate dJNK pathway gain-of-function...

Efferocytosis, the efficient clearance of apoptotic cells (ACs) by phagocytes, is vital for maintaining tissue homeostasis. Here, we reveal role secreted protein NimB1 in reducing cell recognition and binding early stages efferocytosis. expressed macrophages (also called plasmatocytes) binds to ACs a phosphatidylserine-dependent manner. Structural analysis shows that shares striking similarities with bridging molecule NimB4, possesses two phosphatidylserine-binding motifs, supporting its...

Phagoptosis is a frequently occurring nonautonomous cell death pathway in which phagocytes eliminate viable cells. While it thought that phosphatidylserine (PS) "eat-me" signals on target cells initiate the process, precise sequence of events largely unknown. Here, we show Drosophila testes, progenitor germ are spontaneously removed by neighboring cyst through phagoptosis. Using live imaging with multiple markers, demonstrate cell-derived early/late endosomes and lysosomes fused around...

The homothorax (hth) gene is involved in multiple aspects of embryonic and adult fly development. It encodes a homeodomain-containing protein the MEIS family was shown to regulate subcellular localization homeotic cofactor Extradenticle (EXD). HTH contains TALE class homeodomain conserved MH domain, which required for its interaction with EXD. In this work, we describe structure hth locus, characterize at molecular level collection mutant alleles hth, discuss correlation between identified...

During Drosophila embryogenesis, a large number of apoptotic cells are efficiently engulfed and degraded by professional phagocytes, macrophages. Phagocytic receptors SIMU, Drpr Crq specifically expressed in embryonic macrophages required for their phagocytic function. However, how this function is established during development remains unclear. Here we demonstrate that the key regulator hemocyte differentiation, transcription factor Srp, plays central role establishing macrophage...

The proper elimination of unwanted or aberrant cells through apoptosis and subsequent phagocytosis (apoptotic cell clearance) is crucial for normal development in all metazoan organisms. Apoptotic clearance a highly dynamic process intimately associated with death; unengulfed apoptotic are barely seen vivo under conditions. In order to understand the different steps compare 'professional' phagocytes--macrophages dendritic 'non-professional'--tissue-resident neighboring cells, live imaging...

The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress immune signaling, mitochondria homeostasis, death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster Humans. Here, we report that ortholog, dHUWE1 (CG8184), an essential gene whose loss results in embryonic lethality tissue-specific disruption establishes its regulatory...

Skp1, a component of the ubiquitin E3 ligases, was found to be decreased in brains sporadic Parkinson's disease (PD) patients, and its overexpression prevented death murine neurons culture. Here we expose neuroprotective role Drosophila skp1 homolog, skpA, adult brain. Neuronal knockdown skpA leads accumulation ubiquitinated protein aggregates loss dopaminergic accompanied by motor dysfunction reduced lifespan. Conversely, neuronal reduces aggregate load, improves age-related decline,...

Eiger, the sole Drosophila TNF‐alpha homolog, causes ectopic apoptosis through JNK pathway activation. Yet, its role in developmental remains unclear. eiger mutant flies are viable and fertile but display compromised elimination of oncogenic cells extracellular bacteria. Here we show that specifically expressed embryonic neurons glia, is not involved neuronal or apoptotic cell clearance. Instead, provide evidence Eiger required for damage‐induced CNS regulation pro‐apoptotic gene hid...

Programmed cell death plays a fundamental role in development and tissue homeostasis.Professional non-professional phagocytes achieve the proper recognition, uptake, degradation of apoptotic cells, process called efferocytosis.Failure efferocytosis leads to autoimmune neurodegenerative diseases.In Drosophila, two transmembrane proteins Nimrod family, Draper SIMU, mediate recognition internalization corpses.Beyond this early step, little is known about how regulated.Here, we study function...

Glial phagocytosis of apoptotic neurons is crucial for development and proper function the central nervous system. Relying on transmembrane receptors located their protrusions, phagocytic glia recognize engulf debris. Like vertebrate microglia, Drosophila glial cells form an elaborate network in developing brain to reach remove neurons. However, mechanisms controlling creation branched morphology these critical ability remain unknown. Here, we demonstrate that during early embryogenesis,...