Chapter Six Hox Networks and the Origins of Motor Neuron Diversity

Dasen, Jeremy S.; Jessell, Thomas M.

doi:10.1016/s0070-2153(09)88006-x

Cited by 284 publications

(304 citation statements)

References 106 publications

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“…Developmental studies revealed that motoneurons and different sets of interneurons are generated in response to a graded extrinsic signal along the dorso-ventral axis [29][30][31][32] . In the spinal cord, a set of transcription factors controls the features of motoneurons that distinguish them from other neurons 29,33 . These motoneurons are further segregated into motor pools that seem to be determined by Hox transcription factors 30,33,34 .…”

Section: Discussionmentioning

confidence: 99%

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Principles governing recruitment of motoneurons during swimming in zebrafish

et al. 2010

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Locomotor movements are coordinated by a network of neurons that produces sequential muscle activation. Different motoneurons need to be recruited in an orderly manner to generate movement with appropriate speed and force. However, the mechanisms governing the recruitment order have not been fully clarified. Here we show, using an in vitro juvenile/adult zebrafish brainstem-spinal cord preparation, that motoneurons are organized in four pools with specific topographic locations and are incrementally recruited to produce swimming at different frequencies. The threshold of recruitment is not dictated by the input resistance of motoneurons but is rather set by a combination of specific biophysical properties and the strength of the synaptic currents. Thus, our results provide insights into the cellular and synaptic computations governing recruitment of motoneurons during locomotion.3

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Section: Discussionmentioning

confidence: 99%

“…In the spinal cord, a set of transcription factors controls the features of motoneurons that distinguish them from other neurons 29,33 . These motoneurons are further segregated into motor pools that seem to be determined by Hox transcription factors 30,33,34 .…”

Section: Discussionmentioning

confidence: 99%

Principles governing recruitment of motoneurons during swimming in zebrafish

et al. 2010

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“…1) (Kablar and Rudnicki, 1999). While some mechanistic origins of differences in initial MN numbers are known (Dasen and Jessell, 2009;Kanning et al, 2010), evidence for pool-specific regulation of MN survival is still lacking, despite the plethora of factors exerting trophic support on cultured MN subsets (Henderson, 1996;Oppenheim, 1996).…”

Section: Introductionmentioning

confidence: 99%

Pool-Specific Regulation of Motor Neuron Survival by Neurotrophic Support

Lamballe

Genestine²,

Caruso³

et al. 2011

J. Neurosci.

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The precise control of motor neuron (MN) death and survival following initial innervation of skeletal muscle targets is a key step in sculpting a functional motor system, but how this is regulated at the level of individual motor pools remains unclear. Hepatocyte growth factor (HGF) and its receptor Met play key developmental roles in both muscle and MNs. We generated mice (termed "Nes-Met") in which met is inactivated from midembryonic stages onward in the CNS only. Adult animals showed motor behavioral defects suggestive of impaired innervation of pectoral muscles. Correspondingly, in neonatal spinal cords of Nes-Met mutants, we observed death of a discrete population of pea3-expressing MNs at brachial levels. Axonal tracing using pea3 reporter mice revealed a novel target muscle of pea3-expressing MNs: the pectoralis minor muscle. In Nes-Met mice, the pectoralis minor pool initially innervated its target muscle, but required HGF/Met for survival, hence for proper maintenance of muscle innervation. In contrast, HGF/Met was dispensable for the survival of neighboring Met-expressing MN pools, despite its earlier functions for their specification and axon growth. Our results demonstrate the exquisite degree to which outcomes of signaling by receptor tyrosine kinases are regulated on a cell-by-cell basis. They also provide a model for one way in which the multiplicity of neurotrophic factors may allow for regulation of MN numbers in a pool-specific manner.

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“…4F), a marker selectively expressed in MNs of the Hox-sensitive LMC and PGC (47,50,51). Additionally, the Cyp26a1 Ϫ/Ϫ MNs showed a 2 Ϯ 0.4-fold higher (p ϭ 0.02) isl1 mRNA level as compared with the WT MNs at day 7 (Fig.…”

Section: Cyp26a1 Is Necessary For the Establishment Of The Proper Hoxmentioning

confidence: 88%

“…4A and 5A). Expression of Hoxc6 segregates with the brachial (forelimb) LMC MNs, and expression of Hoxc9 segregates with thoracic level PGC MNs, and thus, the LMC and PGC are considered Hox-dependent motor columns (45,50).…”

Section: Discussionmentioning

confidence: 99%

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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Chapter Six Hox Networks and the Origins of Motor Neuron Diversity

Cited by 284 publications

References 106 publications

Principles governing recruitment of motoneurons during swimming in zebrafish

Principles governing recruitment of motoneurons during swimming in zebrafish

Pool-Specific Regulation of Motor Neuron Survival by Neurotrophic Support

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

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