Olig2<sup>+</sup>Precursors Produce Abducens Motor Neurons and Oligodendrocytes in the Zebrafish Hindbrain

Zannino, Denise A.; Appel, Bruce

doi:10.1523/jneurosci.3755-08.2009

Cited by 70 publications

(81 citation statements)

References 61 publications

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“…Taken together, these results reveal that olig2-expressing precursors in the ventromedial hindbrain give rise to both SMNs of the abducens nuclei and OLPs. Recently, a similar analysis of the olig2 lineage in the zebrafish hindbrain (Zannino and Appel, 2009) resulted in the same conclusions.…”

Section: Smns Olps and Astroglia In The Zebrafish Hindbrainmentioning

confidence: 56%

FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9

et al. 2010

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SUMMARYThe mechanisms underlying the generation of neural cell diversity are the subject of intense investigation, which has highlighted the involvement of different signalling molecules including Shh, BMP and Wnt. By contrast, relatively little is known about FGF in this process. In this report we identify an FGF-receptor-dependent pathway in zebrafish hindbrain neural progenitors that give rise to somatic motoneurons, oligodendrocyte progenitors and differentiating astroglia. Using a combination of chemical and genetic approaches to conditionally inactivate FGF-receptor signalling, we investigate the role of this pathway. We show that FGF-receptor signalling is not essential for the survival or maintenance of hindbrain neural progenitors but controls their fate by coordinately regulating key transcription factors. First, by cooperating with Shh, FGF-receptor signalling controls the expression of olig2, a patterning gene essential for the specification of somatic motoneurons and oligodendrocytes. Second, FGF-receptor signalling controls the development of both oligodendrocyte progenitors and astroglia through the regulation of sox9, a gliogenic transcription factor the function of which we show to be conserved in the zebrafish hindbrain. Overall, for the first time in vivo, our results reveal a mechanism of FGF in the control of neural cell diversity.

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Section: Smns Olps and Astroglia In The Zebrafish Hindbrainmentioning

confidence: 56%

FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9

et al. 2010

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“…For this experiment, we used the enhancer trap line Et(hsp(600bp):Gal4-VP16)s1020t, which drives expression in Olig2-expressing neurons (Scott et al, 2007;Wyart et al, 2009). Olig2 is a transcription factor that marks the abducens motor neurons in zebrafish (Zannino and Appel, 2009). Photostimulation of ChR2 in the abducens motor neurons labeled by Et(hsp(600bp): Gal4-VP16)s1020t (Fig.…”

Section: Optical Stimulation Of Abducens Motor Neurons In a Specificmentioning

confidence: 99%

Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish

Schoonheim

Arrenberg²,

Bene³

et al. 2010

J. Neurosci.

167

156

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The optokinetic response (OKR) to a visual stimulus moving at constant velocity consists of a series of two alternating components, a slow phase, during which the eyes follow the stimulus, and a quick phase, which resets the eyes to begin a new response cycle. The quick phases of the OKR resemble the saccades observed during free viewing. It is unclear to what extent the premotor circuitry underlying these two types of jerky, conjugate eye movements is conserved among vertebrates. Zebrafish (Danio rerio) larvae, broadly expressing halorhodopsin (NpHR) or channelrhodopsin-2 (ChR2) in most neurons, were used to map the location of neurons involved in this behavior. By blocking activity in localized groups of NpHR-expressing neurons with an optic fiber positioned above the head of the fish and by systematically varying the site of photostimulation, we discovered that activity in a small hindbrain area in rhombomere 5 was necessary for saccades to occur. Unilateral block of activity at this site affected behavior in a direction-specific manner. Inhibition of the right side suppressed rightward saccades of both eyes, while leaving leftward saccades unaffected, and vice versa. Photostimulation of this area in ChR2-transgenic fish was sufficient to trigger saccades that were precisely locked to the light pulses. These extra saccades could be induced both during free viewing and during the OKR, and were distinct in their kinetics from eye movements elicited by stimulating the abducens motor neurons. Zebrafish double indemnity (didy) mutants were identified in a chemical mutagenesis screen based on a defect in sustaining saccades during OKR. Positional cloning, molecular analysis, and electrophysiology revealed that the didy mutation disrupts the voltage-gated sodium channel Scn1lab (Nav1.lb). ChR2 photostimulation of the putative hindbrain saccade generator was able to fully reconstitute saccades in the didy mutant. Our studies demonstrate that an optogenetic approach is useful for targeted loss-offunction and gain-of-function manipulations of neural circuitry underlying eye movements in zebrafish and that the saccade-generating circuit in this species shares many of its properties with that in mammals.

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“…To assess whether olig2 is required for the development of gad67-positive cells, olig2 translation was knocked down by injection of a previously employed morpholino (Zannino and Appel, 2009). Knockdown of olig2 abolished gad67 expression in KAЈ cells, but gad67 expression was still present in the lateral floor plate (n15 embryos; Fig.…”

Section: The Transcription Factors Tal2 and Olig2 Are Required For Gamentioning

confidence: 99%

Regulatory interactions specifying Kolmer-Agduhr interneurons

2010

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SUMMARYIn the zebrafish spinal cord, two classes of neurons develop from the lateral floor plate: Kolmer-AgduhrЉ (KAЉ) and V3 interneurons. We show here that the differentiation of the correct number of KAЉ cells depends on the activity of the homeobox transcription factor Nkx2.9. This factor acts in concert with Nkx2.2a and Nkx2.2b. These factors are also required for the expression of the zinc-finger transcription factor Gata2 in the lateral floor plate. In turn, Gata2 is necessary for expression of the basic helix-loop-helix transcription factor Tal2 that acts upstream of the GABA-synthesizing enzyme glutamic acid decarboxylase 67 gene (gad67) in KAЉ cells. Expression of the transcription factor Sim1, which marks the V3 interneurons in the lateral floor plate, depends also on the three Nkx2 factors. sim1 expression does not require, however, gata2 and tal2. KAЉ cells of the lateral floor plate and the KAЈ cells located more dorsally in the spinal cord share expression of transcription factors. The functional connections between the different regulatory genes, however, differ in the two GABAergic cell types: although gata2 and tal2 are expressed in KAЈ cells, they are dispensable for gad67 expression in these cells. Instead, olig2 and gata3 are required for the differentiation of gad67-expressing KAЈ cells. This suggests that the layout of regulatory networks is crucially dependent on the lineage that differs between KAЈ and KAЉ cells.

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Olig2⁺Precursors Produce Abducens Motor Neurons and Oligodendrocytes in the Zebrafish Hindbrain

Cited by 70 publications

References 61 publications

FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9

FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9

Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish

Regulatory interactions specifying Kolmer-Agduhr interneurons

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Olig2+Precursors Produce Abducens Motor Neurons and Oligodendrocytes in the Zebrafish Hindbrain

Cited by 70 publications

References 61 publications

FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9

FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9

Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish

Regulatory interactions specifying Kolmer-Agduhr interneurons

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Olig2⁺Precursors Produce Abducens Motor Neurons and Oligodendrocytes in the Zebrafish Hindbrain