Lbx1 Specifies Somatosensory Association Interneurons in the Dorsal Spinal Cord

Groß, Michael; Dottori, Mirella; Goulding, Martyn

doi:10.1016/s0896-6273(02)00690-6

Cited by 361 publications

(535 citation statements)

References 33 publications

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“…However, fibers mediating tactile input from the periphery also synapse extensively with spinal interneurons before reaching the medulla oblongata. Two prominent classes of neurons in the spinal cord contribute to the somatosensory system: dorsal association interneurons and relay neurons [Gross et al, 2002]. Association neurons, that comprise the substantia gelatinosa, predominantly project along the ipsilateral pathways [Brown, 1981;Helms and Johnson, 2003;Szentagothai, 1964], and form a closed system that integrates sensory information within the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

Tactile‐associated fMRI recruitment of the cervical cord in healthy subjects

Valsasina

Caputo

Rocca

et al. 2007

Human Brain Mapping

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Using spinal cord functional magnetic resonance imaging (fMRI), 12 right-handed healthy subjects were scanned during a tactile stimulation of the palm of the right hand. The task-related mean signal change was computed for all activated voxels within the cervical cord, and separately, in the four cord quadrants (right and left anterior, right and left posterior) from C5 to C8. The frequency of fMRI activity at each cord level was obtained by assigning a score of 25% at each active quadrant and by averaging the percentage of active quadrants at each level of all subjects. The difference in the occurrence of fMRI activity (a) in right versus left, and anterior versus posterior cord, and (b) among the different cord levels, was evaluated using a random effect logistic regression model, with the frequency of fMRI activity as the dependent variable and the subject as the grouping factor. The taskrelated mean signal change of all activated voxels of the cord was 3.2% (SD 5 0.8%). During the tactile stimulation, subjects showed a higher occurrence of fMRI cord activity in the right than in the left cervical cord (odds ratio 5 2.25, 95% confidence interval 5 1.31-3.87, P 5 0.003). A significant heterogeneity in frequency of fMRI activity between cord levels was also observed (P < 0.001), with the highest frequencies of fMRI activity detected at C6 and C7. Spinal cord fMRI enables to obtain reliable physiological information on the activity of human spinal circuits associated to tactile stimulation. This holds significant promise for a better planning and conduct of studies of people with diseased spinal cords.

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Section: Discussionmentioning

confidence: 99%

Tactile‐associated fMRI recruitment of the cervical cord in healthy subjects

Valsasina

Caputo

Rocca

et al. 2007

Human Brain Mapping

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“…Lmx1b expression has been employed as a marker of neuronal differentiation in the developing spinal cord. 11,12 To further investigate the role of LMX1B in the neurological symptoms in NPS, the spatiotemporal pattern of Lmx1b was studied using a mouse model with an internal ribosomal entry site (IRES)-LacZ cassette inserted into the 3 0 UTR of the gene. The IRES allows for the translation of both the Lmx1b and b-galactosidase proteins from a single transcript.…”

Section: Introductionmentioning

confidence: 99%

A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression

Dunston

Reimschisel²,

Ding³

et al. 2004

Eur J Hum Genet

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Nail patella syndrome (NPS) is an autosomal dominant disorder affecting development of the limb, kidney and eye. NPS is the result of heterozygous loss-of-function mutations in the LIM-homeodomain transcription factor, LMX1B. Recent studies suggest that the NPS phenotype may be more extensive than recognized previously including neurologic and neurobehavioral aspects. To determine whether these findings correlated with the expression of Lmx1b during development, an internal ribosomal entry siteLacZ reporter was inserted into the 3 0 UTR of the endogenous murine gene. The pattern of Lmx1b expression during the development of the limb, eye and kidney correlates with the NPS phenotype. Additional sites of expression were observed in the central nervous system (CNS). The effects of the absence of Lmx1b in the CNS were determined in lmx1b À/À mice by histology and immunocytochemistry. Lmx1b is required for the differentiation and migration of neurons within the dorsal spinal cord. The inability of afferent sensory neurons to migrate into the dorsal horn is entirely consistent with diminished pain responses in NPS patients.

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“…lhx5 is expressed in several post-mitotic cells in the medial-dorsal region of zebrafish spinal cord, but the exact interneurons that express this gene have not yet been identified (Toyama et al, 1995). In amniotes, Lhx5 is expressed in several different populations of spinal interneurons including V1 cells, the amniote equivalent of CiAs, and more dorsal Pax2-expressing interneurons (Sheng et al, 1997;Gross et al, 2002;Pillai et al, 2007), so it was not surprising that our analysis suggested that this gene is expressed by CiAs. However, to further confirm this result, we performed double in situ hybridisation between lhx5 and eng1b and demonstrated that all CiAs express lhx5 (n ϭ 110 cells in 6 embryos; Fig.…”

Section: Expression-profiling Using Affymetrix Microarraysmentioning

confidence: 85%

“…However, like Lhx5, in amniotes, Lhx1 is expressed in several populations of spinal interneurons, including V1 cells and more dorsal Pax2-expressing interneurons (Sheng et al, 1997;Gross et al, 2002;Pillai et al, 2007), so we had predicted that our analysis might identify this gene as being expressed by CiAs. Interestingly, the lack of differential expression between the Tg(pax2a:GFP) and the Tg(elavl3:EGFP) GFP-positive samples suggests that either not all CiAs express lhx1a at 27 hpf , or that the expression of lhx1a in at least some CiAs is weaker than the expression of this gene in other spinal neurons.…”

Section: Expression-profiling Using Affymetrix Microarraysmentioning

confidence: 99%

“…In both zebrafish and mouse, CiAs/V1 cells are the only spinal cells that express the transcription factor Engrailed-1 (Eng1b in zebrafish, En1 in mouse; Saueressig et al, 1999;Higashijima et al, 2004) and, along with other more dorsal spinal interneurons, CiAs, like V1 cells, also express Pax2 (Burrill et al, 1997;. In addition, mammalian V1 cells express Lhx1 and Lhx5, but it is not yet known whether CiAs also express these transcription factors (Sheng et al, 1997;Gross et al, 2002;Pillai et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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RNA profiling of FAC‐sorted neurons from the developing zebrafish spinal cord

Cerda

Hargrave

Lewis

2008

Developmental Dynamics

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In this report, we describe a successful protocol for isolating and expression-profiling live fluorescentprotein-labelled neurons from zebrafish embryos. As a proof-of-principle for this method, we FAC-sorted and RNA-profiled GFP-labelled spinal CiA interneurons and compared the expression profile of these cells to those of post-mitotic spinal neurons in general and to all trunk cells. We show that RNA of sufficient quality and quantity to uncover both expected and novel transcription profiles via Affymetrix microarray analysis can be extracted from 5,700 to 20,000 FAC-sorted cells. As part of this study, we also further confirm the genetic homology of mammalian and zebrafish V1 interneurons, by demonstrating that zebrafish V1 cells (CiAs) express genes that encode for the transcription factors Lhx1a and Lhx5. This protocol for dissociating, sorting and RNA-profiling neurons from organogenesis-stage zebrafish embryos should also be applicable to other developing organs and tissues and potentially other model organisms. Developmental Dynamics 238:150 -161, 2009.

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Lbx1 Specifies Somatosensory Association Interneurons in the Dorsal Spinal Cord

Cited by 361 publications

References 33 publications

Tactile‐associated fMRI recruitment of the cervical cord in healthy subjects

Tactile‐associated fMRI recruitment of the cervical cord in healthy subjects

A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression

RNA profiling of FAC‐sorted neurons from the developing zebrafish spinal cord

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