Motoneurons Derived from Embryonic Stem Cells Express Transcription Factors and Develop Phenotypes Characteristic of Medial Motor Column Neurons

Soundararajan, Prabakaran; Miles, Gareth B.; Rubin, Lee L.; Brownstone, Robert M.; Rafuse, Victor F.

doi:10.1523/jneurosci.5537-05.2006

Cited by 95 publications

(116 citation statements)

References 62 publications

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“…Our own studies on embryonic stem cell-derived motoneurons found that these neurons in many ways resembled motoneurons (Miles et al, 2004;Soundararajan et al, 2006). These cells demonstrated early SFA, yet were found not to have a measurable AHP conductance (Miles et al, 2004).…”

Section: Spike Frequency Adaptationmentioning

confidence: 94%

Beginning at the end: Repetitive firing properties in the final common pathway

Brownstone

2006

Progress in Neurobiology

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Since the early 20th century, it has been recognized that motoneurons must fire repetitive trains of action potentials to produce muscle contraction. In 1932, Sir John Eccles, together with Hebbel Hoff, found that action potential spike trains in motor axons were produced by "rhythmic centres", which were within the motoneurons themselves. Two decades later, Eccles attended a Cold Spring Harbor Symposium in NY, USA entitled "The Neuron". Two of the many notable presentations at this symposium were juxtaposed: one by Eccles from the University of Otago, Dunedin, NZL, and the other by J. Walter Woodbury and Harry Patton from the University of Washington, Seattle, USA. Both presentations included data obtained using sharp microelectrodes to study the intracellularly recorded potentials of cat motoneurons. In this review, I discuss some of the events leading up to and surrounding this jointly accomplished advance and proceed to discussion of subsequent studies over 5+ decades that have made use of intracellular recordings from motoneurons to study their repetitive firing behavior. This begins with early descriptions of primary and secondary range firing, and continues to the discovery of dendritic persistent inward currents and their relation to plateau potentials, synaptic amplification, and motoneuronal firing. Following a brief description of the possible mechanisms underlying spike frequency adaptation, I discuss the modulation of repetitive firing properties during various motor behaviors. It has become increasingly clear that the central nervous system has exquisite control of the repetitive firing of motoneurons. Eccles' work laid the foundation for the present-day study of these processes.

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Section: Spike Frequency Adaptationmentioning

confidence: 94%

Beginning at the end: Repetitive firing properties in the final common pathway

Brownstone

2006

Progress in Neurobiology

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“…It is generally accepted that ESCs must be directed to differentiate into discrete, neuronal phenotypes that specifically match the properties of the degenerated neurons (7)(8)(9). However, many ESC studies have simply classified neurons by their neurotransmitter phenotype (10).…”

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confidence: 99%

“…However, many ESC studies have simply classified neurons by their neurotransmitter phenotype (10). This classification is often insufficient because subpopulations of neurons that express a given transmitter can vary remarkably with respect to size, ion channels, receptors, projection patterns, and function (9). Therefore, for transplantation studies, it is necessary to direct ESCs to differentiate into distinct, neuronal subtypes.…”

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confidence: 99%

“…Therefore, for transplantation studies, it is necessary to direct ESCs to differentiate into distinct, neuronal subtypes. Cultured wild type (WT) ESCs generally differentiate into MNs that express high Lhx3, a LIM homeodomain (HD) protein characteristic of the median motor column (MMC) (9).…”

mentioning

confidence: 99%

“…For example, WT ESC-derived MNs, treated with all-trans-retinoic acid (RA) and sonic hedgehog (Shh) and transplanted into the developing chick neural tube, express Lhx3, migrate to the MMC, and exhibit functional characteristics of endogenous MMC MNs (9,11). However, little is known about how to differentiate ESCs into LMC neurons, the question we address here.…”

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confidence: 99%

See 2 more Smart Citations

Cytochrome P450 Cyp26a1 Alters Spinal Motor Neuron Subtype Identity in Differentiating Embryonic Stem Cells

Ricard¹,

Gudas

2013

Journal of Biological Chemistry

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Background: How to differentiate embryonic stem cells into specific neuronal types is a key question. Results: Lack of Cyp26a1 results in increased ALDH1a2 and Hoxc6, markers of lateral motor column identity. Conclusion:The cytochrome P450 enzyme Cyp26a1 plays a critical role in specifying motor neuron columnar subtypes. Significance: Blocking Cyp26a1 has therapeutic potential in regenerative medicine, neurodegenerative diseases, and cancer therapies.

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