Thyroid hormone promotes neurogenesis in the <i>Xenopus</i> spinal cord

Schlosser, Gerhard; Koyano-Nakagawa, Naoko; Kintner, Chris

doi:10.1002/dvdy.10179

Cited by 48 publications

(50 citation statements)

References 114 publications

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“…To localize a potential activating ligand for RXR␣ in the CNS, we created transgenic X. laevis expressing the gRXR fusion protein by using the N␤T promoter. The N␤T gene is expressed exclusively in CNS of X. laevis, mainly in postmitotic cells (21,32,33). Using these constructs together with the reporter gene 14XUAS-E1b-EGFP (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…This ligand is transiently synthesized in this region and, hence, activates RXR in a spatial and temporal manner. In this study, we used the N␤T promoter that drives expression of gRXR in postmitotic cells of the central nervous system (21,32,33), whereas in a previous study, expression of gRXR was mostly located in proliferating cells by using the nestin promoter (17). In both cases, activation of gRXR was found in the ventral region of the spinal cord, indicating either a ligand source in both regions or diffusion of the ligand from one region to the other.…”

Section: Discussionmentioning

confidence: 99%

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Spatiotemporal retinoid-X receptor activation detected in live vertebrate embryos

Luria

Furlow

2004

Proc. Natl. Acad. Sci. U.S.A.

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Most studies on the nuclear retinoid-X receptor (RXR) have focused on its role as a heterodimeric partner but less about its own activation pattern during development and the distribution of potential endogenous ligands. The aim of this study is to visualize the distribution of activated RXR␣ in live transgenic Xenopus laevis embryos across a wide range of developmental stages. We adopted a nuclear receptor-Gal4 fusion͞upstream activation sequence-based reporter system for our assay. Strong activation of the RXR␣ ligand-binding domain was observed in a segment of the spinal cord just posterior to the hindbrain. This activation is first detected in neurula stage embryos and persists up to swimming tadpole stages, after which activation strongly declines. Addition of exogenous ligands, such as 9-cis retinoic acid or all-trans retinoic acid, expands the activation of RXR throughout the spinal cord but not in the brain, whereas the RXR-specific ligand LG268 expanded the Gal4 -RXR activation into the brain and olfactory epithelia. Treatment with the RAR-specific ligand 4-(E-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid or thyroid hormone had no effect on Gal4 -RXR activation, whereas these compounds significantly increased their corresponding Gal4͞ receptor fusion proteins under similar conditions. Embryos expressing a Gal4 -RXR fusion protein with a deletion in the liganddependent activation domain (AF2) show no reporter gene activation. The results shown in this paper reveal a specific activation pattern for Gal4 -RXR␣ specifically in the developing spinal cord and suggest the existence of RXR ligand ''hot-spots'' in this region.Gal4 ͉ transgenesis ͉ Xenopus laevis ͉ nuclear receptor

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Spatiotemporal retinoid-X receptor activation detected in live vertebrate embryos

Luria

Furlow

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Therefore, the majority of limb motorneuron generation occurs after the thyroid gland becomes functional, which is around NF stage 46, as determined by its ability to incorporate radioactive iodine (data not shown). A recent study (29) that used published counts of all spinal motorneurons in young tadpoles (30), published counts of limb motorneurons during metamorphosis (9,10), and published measurements of TH levels (31)(32)(33), came to the same conclusion that TH likely regulates the generation of spinal cord cells in tadpoles. However, the fact that RALDH-2 cells are present in small numbers in brachial and lumbar spinal cord even during embryogenesis (data not shown) also suggests that TH may not be required for their generation.…”

Section: Inhibiting Th Function Perturbs the Development Of The Spinamentioning

confidence: 86%

Thyroid hormone controls the development of connections between the spinal cord and limbs during Xenopus laevis metamorphosis

Marsh-Armstrong

Cai

Brown

2003

Proc. Natl. Acad. Sci. U.S.A.

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During premetamorphic stages, Xenopus laevis tadpoles expressing either a dominant-negative thyroid hormone (TH) receptor or a type-III iodothyronine deiodinase transgene in the nervous system have reduced TH-induced proliferation in the spinal cord and produce fewer hindlimb-innervating motorneurons. During prometamorphic stages, innervation of the hindlimbs is reduced, and few functional neuromuscular connections are formed. By metamorphic climax, limb movement is impaired, ranging from uncoordinated leg swimming to complete quadriplegia. This phenotype is due to transgene action in the tadpole spinal cord. The requirement of TH for neurogenesis during premetamorphosis is the earliest TH-regulated process reported to date in the sequence of metamorphic changes in anurans. The muscle formed during limb growth was previously shown to be a direct target of TH control. Here, we show that the same is true of the development of spinal cord cells that innervate the limbs. D uring amphibian metamorphosis, thyroid hormone (TH) controls remodeling of the nervous system (1). TH removes neural circuits that are larval-specific, for example, the spinal cord Rohon-Beard cells (2). TH also promotes the development of cells that participate in frog-specific circuits such as within the olfactory (3), visual (4-7), and auditory (8) systems. In the retina TH acts, in part, by regulating the proliferation of neural progenitors. This action of TH appears to be cell-autonomous, because progenitor cells found in the dorsal retina, but not those found in the ventral retina, are protected from TH action by the precise expression of type-III iodothyronine deiodinase (D3), an enzyme that inactivates TH (7).The spinal cord of anurans is remodeled during metamorphosis. The most dramatic change is the development of neural circuits within the brachial and lumbar spinal cord that control the movement of arms and legs, respectively. The spinal cord cell type that has been most studied during metamorphosis is the limb motorneuron, which is the only spinal cord cell that directly innervates limbs. Limb motorneuron number reach a peak as the limb bud emerges at the beginning of premetamorphosis and then decreases dramatically soon after the limb is innervated (9, 10). To date, it has been unclear whether any change observed in limb motorneurons is due to the action of TH within spinal cord cells. Alternatively, changes in limb motorneurons and other spinal cord cells might be a consequence of the growth and development of limbs, which is a known TH-dependent process.In the current study, we show that inhibiting TH action in the spinal cord by means of neural-specific transgenes leads to a defect in TH-induced neurogenesis, and a decreased generation of lumbar motorneurons that innervate the hindlimb. This defect in neurogenesis is followed by a reduction in hindlimb innervation and a deficiency in functional connections between nerve and muscle within the hindlimb. In terms of hindlimb movement, the phenotypes in these transgenic animals range ...

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“…1C, D, F ). Neither neurogenesis nor cell death can account for differences in the number of immunoreactive neurons per section between stages (Hensey and Gautier, 1998;Schlosser et al, 2002). Thus, the initial expression of GABA and glutamate, but not ChAT and glycine, is promiscuous ( Fig.…”

Section: Neurotransmitters Are Promiscuously Expressed At Early Stagesmentioning

confidence: 99%

Embryonically Expressed GABA and Glutamate Drive Electrical Activity Regulating Neurotransmitter Specification

Root

Velazquez-Ulloa²,

Monsalve³

et al. 2008

J. Neurosci.

106

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Neurotransmitter signaling in the mature nervous system is well understood, but the functions of transmitters in the immature nervous system are less clear. Although transmitters released during embryogenesis regulate neuronal proliferation and migration, little is known about their role in regulating early neuronal differentiation. Here, we show that GABA and glutamate drive calcium-dependent embryonic electrical activity that regulates transmitter specification. The number of neurons expressing different transmitters changes when GABA or glutamate signaling is blocked chronically, either using morpholinos to knock down transmitter-synthetic enzymes or applying pharmacological receptor antagonists during a sensitive period of development. We find that calcium spikes are triggered by metabotropic GABA and glutamate receptors, which engage protein kinases A and C. The results reveal a novel role for embryonically expressed neurotransmitters.

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Thyroid hormone promotes neurogenesis in the Xenopus spinal cord

Cited by 48 publications

References 114 publications

Spatiotemporal retinoid-X receptor activation detected in live vertebrate embryos

Spatiotemporal retinoid-X receptor activation detected in live vertebrate embryos

Thyroid hormone controls the development of connections between the spinal cord and limbs during Xenopus laevis metamorphosis

Embryonically Expressed GABA and Glutamate Drive Electrical Activity Regulating Neurotransmitter Specification

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