A5038667422- Neurobiology and Insect Physiology Research
- Developmental Biology and Gene Regulation
- Nerve injury and regeneration
- Axon Guidance and Neuronal Signaling
- Invertebrate Immune Response Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Cell Image Analysis Techniques
- Neuroscience and Neuropharmacology Research
- Signaling Pathways in Disease
- Hedgehog Signaling Pathway Studies
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Silk-based biomaterials and applications
- Receptor Mechanisms and Signaling
- Plant Molecular Biology Research
- Microtubule and mitosis dynamics
- Animal Behavior and Reproduction
- Animal Genetics and Reproduction
- Digital Imaging for Blood Diseases
- Neuroscience and Neural Engineering
- Zebrafish Biomedical Research Applications
- Congenital limb and hand anomalies
- Antimicrobial Peptides and Activities
- Advanced Fluorescence Microscopy Techniques
University of Birmingham
2015-2025
NeuroDevelopment Center
2013-2020
University of Sussex
2018
University of Cambridge
1995-2004
The Gurdon Institute
1995-1997
Wellcome Trust
1996
Centro de Biología Molecular Severo Ochoa
1994
University of Oxford
1991
Charing Cross Hospital
1988
Abstract Intrasegmental patterning in the Drosophila embryo requires activity of segment polarity genes. The acquisition positional information by cells during embryogenesis is reflected dynamic patterns expression several these In case patched, early ubiquitous followed its repression anterior portion each parasegment; subsequently broad band splits into two narrow stripes. this study we analyse contribution other gene functions to evolution pattern; find that first step patched regulation...
Experience alters brain structure, but the underlying mechanism remained unknown. Structural plasticity reveals that function is encoded in generative changes to cells compete with destructive processes driving neurodegeneration. At an adult critical period, experience increases fiber number and size Drosophila. Here, we asked if Toll receptors are involved. Tolls demarcate a map of anatomical domains. Focusing on Toll-2, loss caused apoptosis, neurite atrophy impaired behaviour. Toll-2 gain...
ABSTRACT The segment polarity gene wingless (wg) is expressed in a complex pattern during embryogenesis suggesting that it plays multiple roles the development of embryo. best characterized these its role cell pattening each parasegment, process requires activity other genes including patched (ptc) and hedgehog (hh). Here we present further evidence ptc hh encode components signal transduction pathway regulate expression wg transcription following activation by pair-rule genes. We also show...
ABSTRACT Glial cells are thought to play a role in growth cone guidance, both insects and vertebrates. In the developing central nervous system of Drosophila embryo, interface glia form scaffold prior extension first pioneer cones. Growing axons appear contact glial as axon tracts established. We have used novel technique for targeted cell ablation kill thus test their establishment embryonic tracts. show that early development leads complete loss longitudinal Ablation later results defects...
ABSTRACT Although pioneer neurons are the first to delineate axon pathways, it is uncertain whether they have unique pathfinding abilities. As a step in defining role of Drosophila embryonic CNS, we describe temporal profile and trajectory axons four show that differ from previously published reports. We show, by targeted ablation one, two, three or at time, (1) no single neuron essential for tract formation, (2) interaction between two pioneers necessary establishment each fascicle (3)...
Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory cognition. We have identified a flies, Drosophila Neurotrophin (DNT1), structurally related all known neurotrophins highly conserved insects. By investigating with genetics consequences of removing DNT1 or...
ABSTRACT While survival of CNS neurons appears to depend on multiple neuronal and non-neuronal factors, it remains largely unknown how is controlled during development. Here we show that glia regulate formation the Drosophila embryonic CNS. When glial function impaired either by mutation cells missing gene, which transforms toward a fate, or targeted genetic ablation, death induced non-autonomously. Pioneer neurons, establish first longitudinal axon fascicles, are insensitive depletion...
ABSTRACT Whereas considerable progress has been made in understanding the molecular mechanisms of axon guidance across midline, it is still unclear how axonal trajectories longitudinal pioneer neurons, which never cross are established. Here we show that glia embryonic Drosophila CNS direct formation pathways. By ablation and analysis glial cells missing mutants, demonstrate required for two kinds processes. Firstly, growth cone guidance, although this requirement not absolute. We route...
Organisms are structurally robust, as cells accommodate changes preserving structural integrity and function. The molecular mechanisms underlying robustness plasticity poorly understood, but can be investigated by probing how respond to injury. Injury the CNS induces proliferation of enwrapping glia, leading axonal re-enwrapment partial functional recovery. This glial regenerative response is found across species, may reflect a common genetic mechanism. Here, we show that injury Drosophila...
Cell number plasticity is coupled to circuitry in the nervous system, adjusting cell mass functional requirements. In mammals, this achieved by neurotrophin (NT) ligands, which promote survival via their Trk and p75NTR receptors death Sortilin. Drosophila NTs (DNTs) bind Toll instead neuronal survival, but whether they can also regulate unknown. study, we show that DNTs Tolls switch from promoting central system (CNS) a three-tier mechanism. First, DNT cleavage patterns result alternative...
Retrograde growth factors regulating synaptic plasticity at the neuromuscular junction (NMJ) in Drosophila have long been predicted but their discovery has scarce. In vertebrates, such retrograde produced by muscle include GDNF and neurotrophins (NT: NGF, BDNF, NT3 NT4). NT superfamily members identified throughout invertebrates, so far no functional vivo analysis carried out NMJ invertebrates. The family of proteins is formed DNT1, DNT2 Spätzle (Spz), with sequence, structural conservation...
Central nervous system injury induces a regenerative response in ensheathing glial cells comprising cell proliferation, spontaneous axonal remyelination, and limited functional recovery, but the molecular mechanisms are not fully understood. In Drosophila, this involves genes prospero Notch controlling balance between proliferation differentiation, manipulating their levels glia can switch to from prevention promotion of repair. mouse, Notch1 maintains NG2 oligodendrocyte progenitor (OPCs)...
Neuron glia antigen 2 (NG2)–positive are repair cells that proliferate upon central nervous system (CNS) damage, promoting functional recovery. However, is limited because of the failure newly produced glial to differentiate. It a key goal discover how regulate NG2 enable proliferation and differentiation conducive repair. Drosophila has an homologue called kon-tiki (kon), unknown CNS function. We show kon promotes identify underlying mechanism. Crush injury up-regulates expression...
Contrary to our knowledge of the genetic control midline crossing, mechanisms that generate and maintain longitudinal axon pathways Drosophila CNS are largely unknown. The formed by ipsilateral pioneer axons glia. glia dictate these axonal trajectories provide trophic support later projecting follower neurons. Follower interneuron cross once join form connectives. Once on contralateral side, repelled from recrossing repulsive signal Slit its receptor Roundabout. We show also transiently...
Abstract Evidence of molecular and functional homology between vertebrate Drosophila glia is limited, restricting the power as a model system to unravel basis glial function. Like in vertebrates, central nervous cells are produced excess surplus eliminated by apoptosis adjusting final number axons. The underlying mechanisms largely unknown, only gliatrophic pathway known date flies EGFR its ligands. PDGFR signaling plays major role regulating oligodendrocyte migration vertebrates. Here, we...