2018 Group Project 5

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Projects 2018: 1 Adrenal Medulla | 3 Melanocytes | 4 Cardiac | 5 Dorsal Root Ganglion

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Dorsal Root Ganglion

Introduction

Dorsal Root Ganglion is a cluster of neurone found in the dorsal root of the spinal nerve. The cells found in the ganglion develops from the neural crest migration at about 4 weeks post-conception (pc).

History

Embryonic Origins

Developmental Process

Neural Crest Migration in Formation of the DRG

Trunk neural crest cells migrate via a ventromedial pathway on the neural tube during the fourth week of development. Depending on where these cells cease their migration will determine the structure into which they develop. The neural crest cells that will divide to form the dorsal root ganglion cease ventral migration once they have reached the area of the perisomitic vessel between the neural tube and the somites. [1].

A diagram displaying the developing dorsal root ganglion and ventricular zone in a mouse embryo 12.5 days after fertilization.

Progenitor cells act as the beginning catalysts that lead the neural crest cells to differentiate into the neurons and glial cells that will comprise the DRG. Sox10+ progenitors are one of the most common progenitors that plays a role in the differentiation of the neural crest cells first into neurons and then in glia. TrkA, a nociceptor, and TrkB/TrkC, mechanoreceptors and proprioceptors, are the three classes of neurons that form the DRG following the end of the neural crest migration.[2]. The precursors that shape the development of TrkB and TrkC neurons are produced first, followed quickly by the precursors that shape the development of TrkA.[3].

Ngn1 and Ngn2 are transcription factors that shape DRG's role in the sensory system. Ngn1 helps to enhance the transcription of the mylinated TrkB,TrkC, and TrkA axons, while Ngn1 follows this action with control of both nonmylinated and mylinated axons. Furthermore, the morphogen Wnt1 is also recognized as having an important role in sensory development.[3].

Neuron Development

The SOX2 transcription factor plays a large role in the individual differentiation of of the neuronal and glial populations within the Dorsal Root Ganglion.

Glial Development

Adult Function

Tissue / Organ Structure

Molecular Mechanisms / Factors / Genes

CXCR4 Chemokine Receptor

Abnormalities / Abnormal Development

Dorsal Root Ganglionopathy is responsible for the sensory impairment

Dorsal Root Ganglionopathy is responsible for sensory impairment in CANVAS

Dorsal Root Ganglion disorder.jpg

"Sensory ganglionitis, variably called ganglionopathy, is a disease of sensory neurons in dorsal root ganglia. Major forms of these diseases are associated with neoplasm, Sjögren syndrome, and paraproteinemia or polyclonal gammopathy with or without known autoantibodies. Most cases follow subacute courses, but there are forms that develop chronically and acutely as well. Clinical signs seen include sensory ataxia exhibited by gait unsteadiness, a positive Romberg sign, reduced deep tendon reflexes, poor coordination, and pseudo-athetoid movements in the hands. Axonal degeneration warrants the treatment as early as possible. Early cases of immunologic origin that are immune-mediated may respond to plasmapheresis and immunosuppression. Differential diagnoses include environmental and industrial intoxication and adverse effects of antineoplastic and antibiotic drugs. The term “sensory neuronopathy” or “ganglionitis” refers to disorders of small neurons, larger neurons, and/or neurons of both sizes in the sensory ganglia."

Animal Models

Zebrafish Model

Comparison of neural crest cell migration between erbb3b mutants and wildtype zebrafish models.

Current Research (Labs)

Link on current research for DRG [4]

Microphotograph of dorsal root ganglion from a frozen section including DRG neurons and satellite cells.

Glossary

Reference List

[5] [6] [7] [1] [8] [4] [2] [3] [9] [10]

  1. 1.0 1.1 Kasemeier-Kulesa JC, Kulesa PM & Lefcort F. (2005). Imaging neural crest cell dynamics during formation of dorsal root ganglia and sympathetic ganglia. Development , 132, 235-45. PMID: 15590743 DOI.
  2. 2.0 2.1 Gonsalvez DG, Li-Yuen-Fong M, Cane KN, Stamp LA, Young HM & Anderson CR. (2015). Different neural crest populations exhibit diverse proliferative behaviors. Dev Neurobiol , 75, 287-301. PMID: 25205394 DOI.
  3. 3.0 3.1 3.2 Marmigère F & Carroll P. (2014). Neurotrophin signalling and transcription programmes interactions in the development of somatosensory neurons. Handb Exp Pharmacol , 220, 329-53. PMID: 24668479 DOI.
  4. 4.0 4.1 Sapunar D, Kostic S, Banozic A & Puljak L. (2012). Dorsal root ganglion - a potential new therapeutic target for neuropathic pain. J Pain Res , 5, 31-8. PMID: 22375099 DOI.
  5. George L, Dunkel H, Hunnicutt BJ, Filla M, Little C, Lansford R & Lefcort F. (2016). In vivo time-lapse imaging reveals extensive neural crest and endothelial cell interactions during neural crest migration and formation of the dorsal root and sympathetic ganglia. Dev. Biol. , 413, 70-85. PMID: 26988118 DOI.
  6. George L, Kasemeier-Kulesa J, Nelson BR, Koyano-Nakagawa N & Lefcort F. (2010). Patterned assembly and neurogenesis in the chick dorsal root ganglion. J. Comp. Neurol. , 518, 405-22. PMID: 20017208 DOI.
  7. Ogawa R, Fujita K & Ito K. (2017). Mouse embryonic dorsal root ganglia contain pluripotent stem cells that show features similar to embryonic stem cells and induced pluripotent stem cells. Biol Open , 6, 602-618. PMID: 28373172 DOI.
  8. Kasemeier-Kulesa JC, McLennan R, Romine MH, Kulesa PM & Lefcort F. (2010). CXCR4 controls ventral migration of sympathetic precursor cells. J. Neurosci. , 30, 13078-88. PMID: 20881125 DOI.
  9. Szmulewicz DJ, McLean CA, Rodriguez ML, Chancellor AM, Mossman S, Lamont D, Roberts L, Storey E & Halmagyi GM. (2014). Dorsal root ganglionopathy is responsible for the sensory impairment in CANVAS. Neurology , 82, 1410-5. PMID: 24682971 DOI.
  10. Cimadamore F, Fishwick K, Giusto E, Gnedeva K, Cattarossi G, Miller A, Pluchino S, Brill LM, Bronner-Fraser M & Terskikh AV. (2011). Human ESC-derived neural crest model reveals a key role for SOX2 in sensory neurogenesis. Cell Stem Cell , 8, 538-51. PMID: 21549328 DOI.