Cellular and molecular anatomy of the human neuromuscular junction

About the project

The neuromuscular junction (NMJ) is the synapse formed between a lower motor neuron and a skeletal muscle fibre. The NMJ is known to be an early target in a number of conditions including motor neurone disease (MND), with most research into these conditions utilizing animal (rodent) models of disease. Our work to date has uncovered significant differences in the cellular and molecular anatomy of the human NMJ as compared with rodent NMJs, with major implications for translational work. A better understanding of these similarities and differences will aid in the translation of therapies developed in animal models to patients with MND.

Publication(s)

Cahalan SD

Boehm I

Jones RA

Piercy RJ

Recognising the potential of large animals for modelling neuromuscular junction physiology and disease

Journal of Anatomy

2022 Sep 02

DOI: 10.1111/joa.13749

Cahalan SD, Perkins J, Boehm I, Jones RA, Gillingwater TH, Piercy RJ

A method to identify, dissect and stain equine neuromuscular junctions for morphological analysis

Journal of Anatomy

2022 Sep 29

DOI: 10.1111/joa.13747

Roesl C, Evans ER, Dissanayake KN, Boczanadi V, Jones RA, Jordan GR, Ledahawsky L, Allen GCC, Scott M, Thomson A, Wishart TM

Hughes DI, Mead RJ, Shone CC, Slater CR, Gillingwater TH, Skehel PA, Ribchester RR

Confocal endomicroscopy of neuromuscular junctions stained with physiologically inert protein fragments of tetanus toxin

Biomolecules. 11, 1499

2021 Oct 12

DOI: 10.3390/biom11101499

Alhindi A, Boehm I, Forsythe RO, Miller J, Skipworth RJE, Simpson H, Jones RA, Gillingwater TH

Terminal Schwann Cells at the Human Neuromuscular Junction

Brain Communications (open access)

2021 Apr 15

DOI: 10.1093/braincomms/fcab081

Boehm I, Alhindi A, Leite AS, Logie C, Gibbs A, Murray O, Farrukh R, Pirie R, Proudfoot C, Clutton R, Wishart TM, Jones RA, Gillingwater TH

Comparative anatomy of the mammalian neuromuscular junction

Journal of Anatomy (open access)

2020 Jun 20

DOI: 10.1111/joa.13260

Boehm I, Miller J, Wishart TM, Wigmore SJ, Skipworth RJE, Jones RA, Gillingwater TH

Neuromuscular junctions are stable in patients with cancer cachexia

Journal of Clinical Investigation

2019 Dec 03

DOI: 10.1172/JCI128411

Minty G, Hoppen A, Boehm I, Alhindi A, Gibb L, Potter E, Wagner B, Miller J, Skipworth R, Gillingwater TH, Jones RA

aNMJ-morph: a simple macro for rapid analysis of neuromuscular junction morphology

Royal Society Publishing (op[en access)

2020 Apr 15

DOI: 10.1098/rsos.200128

Jones RA, Harrison C, Eaton SL, Hurtado ML, Graham LC, Alkhammash L, Oladiran OA, Gale A, Lamont DJ, Simpson H, Simmen MW, Soeller C, Wishart TM, Gillingwater TH

Cellular and Molecular Anatomy of the Human Neuromuscular Junction

Cell Reports (open access)

2017 Nov 28

DOI: 10.1016/j.celrep.2017.11.008

Jones RA, Reich CD, Dissanayake KN, Kristmundsdottir F, Findlater GS, Ribchester RR, Simmen MW, Gillingwater TH

NMJ-morph reveals principal components of synaptic morphology influencing structure-function relationships at the neuromuscular junction

Open Biology (open access)

2016 Dec 06

DOI: 10.1098/rsob.160240

Hunter G, Powis RA, Jones RA, Groen EJN, Shorrock HK, Lane FM, Zheng Y, Sherman DL, Brophy PJ, Gillingwater TH

Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy.

Human Molecular Genetics

2016 Jul 01

DOI: 10.1093/hmg/ddw141

Powis RA, Karyka E, Boyd P, Côme J, Jones RA, Zheng Y, Szunyogova E, Groen EJN, Hunter G, Gillingwater TH, et al

Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy

JCI InSight (open access)

2016 Jul 21

DOI: 10.1172/jci.insight.87908

Alhindi A, Shand M, Smith HL, Leite AS, Huang HT, van der Hoorn D, Ridgway Z, Faller KME, Jones RA, Gillingwater TH, Chaytow H.

Neuromuscular junction denervation and terminal Schwann cell loss in the hTDP-43 overexpression mouse model of amyotrophic lateral sclerosis (ALS)

Neuropathology and Applied Neurobiology (2023)

2023 Aug 01

DOI: 10.1111/nan.12925

Jones RA, Ramadan A, Qutifan S, Gillingwater TH

Neuromuscular impairment at different stages of human sarcopenia

Journal of Cachexia, Sarcopenia and Muscle (2024)

2024 Dec 15

DOI: 10.1002/jcsm.13624

Primary location

Edinburgh

Principal Investigator

Dr Ross Jones

Other people involved

University of Edinburgh

Thomas Gillingwater, Edinburgh Medical School
Philippa Rust, Department of Orthopaedic Surgery NHS Lothian, St John's Hospital, Livingston
Shahd Qutifan, PhD Student
Abdullah Ramadan, PhD Student

University of New South Wales

Izzy Jayasinghe, Molecular Medicine