<i>Lmx1b</i>controls the differentiation and migration of the superficial dorsal horn neurons of the spinal cord

Ding, Yu; Yin, Jun; Kania, Artur; Zhao, Zhong Qiu; Johnson, Randy L.; Chen, Zhou Feng

doi:10.1242/dev.01250

Cited by 97 publications

(76 citation statements)

References 68 publications

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“…Consistent with results in mouse [16, 18, 32, 62–64, 87], we demonstrate here that in the zebrafish spinal cord lmx1bb is predominantly expressed by glutamatergic neurons (Fig. 1j and k).…”

Section: Discussionsupporting

confidence: 92%

“…Also consistent with results in amniotes [16, 18, 32, 62–64, 87], our analyses suggest that a subset of lmx1b- expressing spinal cord cells are dI5 cells. dI5 cells constitute about a third of all Lbx1- expressing spinal cord cells and they are also the only excitatory, Lbx1 -expressing spinal cells [8–10, 16].…”

Section: Discussionsupporting

confidence: 91%

“…However, while data from previous studies suggested that Lmx1b may have a role in the development of a subset of spinal cord glutamatergic cells (e.g. [8, 9, 18, 62]), a precise function in glutamatergic fate specification or maintenance had not been identified. Interestingly, when Lmx1b was conditionally ablated specifically in the mouse spinal cord, at E18.5 there was also a reduction in the number of glutamatergic neurons and no change in the number of inhibitory neurons, which is similar to our results in zebrafish (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Prior to this study, Lmx1b had been implicated in correct neuronal migration, connectivity and viability [18, 19, 25, 62, 88, 89]. However, while data from previous studies suggested that Lmx1b may have a role in the development of a subset of spinal cord glutamatergic cells (e.g.…”

Section: Discussionmentioning

confidence: 99%

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Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons

et al. 2016

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BackgroundAlterations in neurotransmitter phenotypes of specific neurons can cause imbalances in excitation and inhibition in the central nervous system (CNS), leading to diseases. Therefore, the correct specification and maintenance of neurotransmitter phenotypes is vital. As with other neuronal properties, neurotransmitter phenotypes are often specified and maintained by particular transcription factors. However, the specific molecular mechanisms and transcription factors that regulate neurotransmitter phenotypes remain largely unknown.MethodsIn this paper we use single mutant, double mutant and transgenic zebrafish embryos to elucidate the functions of Lmx1ba and Lmx1bb in the regulation of spinal cord interneuron neurotransmitter phenotypes.ResultsWe demonstrate that lmx1ba and lmx1bb are both expressed in zebrafish spinal cord and that lmx1bb is expressed by both V0v cells and dI5 cells. Our functional analyses demonstrate that these transcription factors are not required for neurotransmitter fate specification at early stages of development, but that in embryos with at least two lmx1ba and/or lmx1bb mutant alleles there is a reduced number of excitatory (glutamatergic) spinal interneurons at later stages of development. In contrast, there is no change in the numbers of V0v or dI5 cells. These data suggest that lmx1b-expressing spinal neurons still form normally, but at least a subset of them lose, or do not form, their normal excitatory fates. As the reduction in glutamatergic cells is only seen at later stages of development, Lmx1b is probably required either for the maintenance of glutamatergic fates or to specify glutamatergic phenotypes of a subset of later forming neurons. Using double labeling experiments, we also show that at least some of the cells that lose their normal glutamatergic phenotype are V0v cells. Finally, we also establish that Evx1 and Evx2, two transcription factors that are required for V0v cells to acquire their excitatory neurotransmitter phenotype, are also required for lmx1ba and lmx1bb expression in these cells, suggesting that Lmx1ba and Lmx1bb act downstream of Evx1 and Evx2 in V0v cells.ConclusionsLmx1ba and Lmx1bb function at least partially redundantly in the spinal cord and three functional lmx1b alleles are required in zebrafish for correct numbers of excitatory spinal interneurons at later developmental stages. Taken together, our data significantly enhance our understanding of how spinal cord neurotransmitter fates are regulated.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons

et al. 2016

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“…In addition, a subset expresses PhoxA2 (Ding et al, 2004). These interneurons were previously known as D4.…”

Section: Dorsal Interneuron Progenitorsmentioning

confidence: 99%

Molecular and cellular development of spinal cord locomotor circuitry

Niu

Alaynick

2015

Front. Mol. Neurosci.

174

209

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The spinal cord of vertebrate animals is comprised of intrinsic circuits that are capable of sensing the environment and generating complex motor behaviors. There are two major perspectives for understanding the biology of this complicated structure. The first approaches the spinal cord from the point of view of function and is based on classic and ongoing research in electrophysiology, adult behavior, and spinal cord injury. The second view considers the spinal cord from a developmental perspective and is founded mostly on gene expression and gain-of-function and loss-of-function genetic experiments. Together these studies have uncovered functional classes of neurons and their lineage relationships. In this review, we summarize our knowledge of developmental classes, with an eye toward understanding the functional roles of each group.

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Molecular Genetics of Nail–Patella Syndrome

McIntosh¹

2012

Encyclopedia of Life Sciences

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Nail–patella Syndrome (NPS) is a pleiotropic disorder affecting development of the limbs, kidneys, eyes and central nervous system, which is the result of heterozygous, loss‐of‐function mutations in the transcription factor, LIM‐homeobox 1β (LMX1B). There is no correlation between the type or nature of individual mutations and the severity of the phenotype. The availability of animal models, together with analysis of gene expression patterns during development, has substantiated that the range of clinically relevant signs and symptoms is greater than appreciated previously. Evidence is building that attention deficit±hyperactivity disorder and depression may be constituent parts of the syndrome. The variation in the range and severity of symptoms, and the diverse range of affected tissues, make NPS an appropriate model in which to study the effects of gene interactions on the observed phenotype. Key Concepts: NPS is a pleiotropic, clinically variable autosomal dominant disorder. LMX1B is a member of a gene family primarily involved in regulating neuronal patterning. Loss of function mutations in LMX1B cause NPS but do not predict disease severity. Analysis of Lmx1b expression has helped explain previously unknown neural aspects of NPS. Physicians should be aware of the extra‐skeletal aspects of NPS and institute appropriate monitoring and treatment.

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Lmx1bcontrols the differentiation and migration of the superficial dorsal horn neurons of the spinal cord

Cited by 97 publications

References 68 publications

Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons

Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons

Molecular and cellular development of spinal cord locomotor circuitry

Molecular Genetics of Nail–Patella Syndrome

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