Domain-specific regulation of foxP2 CNS expression by lef1

Bonkowsky, Joshua L.; Wang, Xu; Fujimoto, E.; Lee, Ji Eun; Chien, Chi Bin; Dorsky, Richard I.

doi:10.1186/1471-213x-8-103

Cited by 54 publications

(75 citation statements)

References 54 publications

(81 reference statements)

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“…Specific plasmids used for cloning were: p5E- otpb.A (Fujimoto et al, 2011), pME- nsfB (no stop codon) (kind gift of C. Seiler), p3E- EGFPpA and pDestTol2pA2 (Kwan et al, 2007). Injection of DNA constructs and husbandry of stable transgenic lines were performed as previously described (Bonkowsky et al, 2008). All procedures were approved by the Institutional Animal Care and Use Committees (IACUC) at the University of Minnesota and the University of Utah.…”

Section: Methodsmentioning

confidence: 99%

The Conserved Dopaminergic Diencephalospinal Tract Mediates Vertebrate Locomotor Development in Zebrafish Larvae

Lambert

Bonkowsky

Masino³

2012

J. Neurosci.

134

176

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The most conserved part of the vertebrate dopaminergic system is the orthopedia (otp)-expressing diencephalic neuronal population that constitutes the dopaminergic diencephalospinal tract (DDT). While studies in the neonatal murine spinal cord in vitro suggest an early locomotor role of the DDT, the function of the DDT in developing vertebrates in vivo remains unknown. Here, we investigated the role of the DDT in the locomotor development of zebrafish larvae. To assess the development of the behavioral and neural locomotor pattern, we employed high-throughput video-tracking in combination with peripheral nerve recordings. We found a behavioral and neural correspondence in the developmental switch from an immature to mature locomotor pattern. Blocking endogenous dopamine receptor 4 (D4R) signaling in vivo either before or after the developmental switch prevented or reversed the switch, respectively. Spinal transections of post-switch larvae reestablished the immature locomotor pattern, which was rescued to a mature-like pattern via spinal D4R agonism. Selective chemogenetic ablation of otp b (otpb) neurons that contribute to the DDT perpetuated the immature locomotor pattern in vivo. This phenotype was recapitulated by diencephalic transections that removed the dopaminergic otpb population and which were rescued to a mature-like locomotor pattern by D4R agonism. We conclude that the dopaminergic otpb population, via the DDT, is responsible for spinal D4R signaling to mediate the developmental switch to the mature locomotor pattern of zebrafish. These results, integrated with the mammalian literature, suggest that the DDT represents an evolutionarily conserved neuromodulatory system that is necessary for normal vertebrate locomotor development.

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Section: Methodsmentioning

confidence: 99%

The Conserved Dopaminergic Diencephalospinal Tract Mediates Vertebrate Locomotor Development in Zebrafish Larvae

Lambert

Bonkowsky

Masino³

2012

J. Neurosci.

134

176

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“…Injection of DNA constructs and generation of stable transgenic lines was performed essentially as described [17]. Lines are available upon request.…”

Section: Methodsmentioning

confidence: 99%

Hypoxia Disruption of Vertebrate CNS Pathfinding through EphrinB2 Is Rescued by Magnesium

et al. 2012

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The mechanisms of hypoxic injury to the developing human brain are poorly understood, despite being a major cause of chronic neurodevelopmental impairments. Recent work in the invertebrate Caenorhabditis elegans has shown that hypoxia causes discrete axon pathfinding errors in certain interneurons and motorneurons. However, it is unknown whether developmental hypoxia would have similar effects in a vertebrate nervous system. We have found that developmental hypoxic injury disrupts pathfinding of forebrain neurons in zebrafish (Danio rerio), leading to errors in which commissural axons fail to cross the midline. The pathfinding defects result from activation of the hypoxia-inducible transcription factor (hif1) pathway and are mimicked by chemical inducers of the hif1 pathway or by expression of constitutively active hif1α. Further, we found that blocking transcriptional activation by hif1α helped prevent the guidance defects. We identified ephrinB2a as a target of hif1 pathway activation, showed that knock-down of ephrinB2a rescued the guidance errors, and showed that the receptor ephA4a is expressed in a pattern complementary to the misrouting axons. By targeting a constitutively active form of ephrinB2a to specific neurons, we found that ephrinB2a mediates the pathfinding errors via a reverse-signaling mechanism. Finally, magnesium sulfate, used to improve neurodevelopmental outcomes in preterm births, protects against pathfinding errors by preventing upregulation of ephrinB2a. These results demonstrate that evolutionarily conserved genetic pathways regulate connectivity changes in the CNS in response to hypoxia, and they support a potential neuroprotective role for magnesium.

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“…p5E-10xUAS, pME-dcc m , and p3E-pA were recombined into pDestTol2CG2, which provided Tol2 transposon ends and a cmlc2: EGFP transgenesis marker. Injection of this DNA construct and generation of the stable transgenic line Tg( UAS:dcc m ; myl7:EGFP ) zc79 was performed as described in Bonkowsky et al (2008).…”

Section: Methodsmentioning

confidence: 99%

Netrin/DCC Signaling Guides Olfactory Sensory Axons to Their Correct Location in the Olfactory Bulb

Lakhina¹,

Marcaccio²,

Shao³

et al. 2012

J. Neurosci.

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Olfactory sensory neurons expressing particular olfactory receptors project to specific reproducible locations within the bulb. The axonal guidance cues that organize this precise projection pattern are only beginning to be identified. To aid in their identification and characterization, we generated a transgenic zebrafish line, OR111-7:IRES:Gal4, in which a small subset of olfactory sensory neurons is labeled. Most sensory neurons expressing the OR111-7 transgene project to a specific location within the bulb, the central zone protoglomerulus, while a smaller number project to the LG1 protoglomerulus. Inhibiting netrin/DCC signaling perturbs the ability of OR111-7 expressing axons to enter the olfactory bulb and alters their patterns of termination within the bulb. The netrin receptor DCC is expressed in olfactory sensory neurons around the time that they elaborate their axons, netrin1a is expressed near the medial-most margin of the olfactory bulb, and netrin1b is expressed within the ventral region of the bulb. Loss of netrin/DCC signaling components causes some OR111-7 expressing sensory axons to wander posteriorly after exiting the olfactory pit, away from netrin expressing areas in the bulb. OR111-7 expressing axons that enter the bulb target the central zone less precisely than normal, spreading away from netrin expressing regions. These pathfinding errors can be corrected by the re-expression of DCC within OR111-7 transgene expressing neurons in DCC morphant embryos. These findings implicate netrins as the only known attractants for olfactory sensory neurons, first drawing OR111-7 expressing axons into the bulb and then into the ventromedially positioned central zone protoglomerulus.

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Domain-specific regulation of foxP2 CNS expression by lef1

Cited by 54 publications

References 54 publications

The Conserved Dopaminergic Diencephalospinal Tract Mediates Vertebrate Locomotor Development in Zebrafish Larvae

The Conserved Dopaminergic Diencephalospinal Tract Mediates Vertebrate Locomotor Development in Zebrafish Larvae

Hypoxia Disruption of Vertebrate CNS Pathfinding through EphrinB2 Is Rescued by Magnesium

Netrin/DCC Signaling Guides Olfactory Sensory Axons to Their Correct Location in the Olfactory Bulb

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