Hypocretin underlies the evolution of sleep loss in the Mexican cavefish

Jaggard, James B.; Stahl, Bethany A.; Lloyd, Evan; Duboué, Erik R.; Keene, Alex C.

doi:10.1101/122903

Cited by 28 publications

(65 citation statements)

References 64 publications

(9 reference statements)

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“…The identification of these circuits allows for cell-autonomous manipulation of gene function, or optogenetic manipulation of behaviorally relevant neurons. In A. mexicanus a number of genes have been implicated in behavior including a role for Mc4r in feeding, hypocretin in sleep, and monoaminergic signaling in aggression [6,36,37]. While presumably the neurons expressing these genes are implicated in behavior, a lack of transgenic accessibility represents a fundamental impediment to mechanistic investigation.…”

Section: Discussionmentioning

confidence: 99%

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Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system

Stahl

Peuß

McDole

et al. 2019

Preprint

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Astyanax mexicanus is a well-established and widely used fish model system for evolutionary and developmental biology research. These fish exist as surface forms that inhabit rivers and 30 different populations of cavefish. The establishment of A. mexicanus as an emergent model organism for understanding the evolutionary basis of development and behavior has been accelerated by an increasing availability of genomic approaches to identify genotype-phenotype associations. Despite important progress in the deployment of new technologies, deep mechanistic insights into A. mexicanus evolution and development have been limited by a lack of transgenic lines commonly used in genetic model systems. Here, we expand the toolkit of transgenesis by characterizing two novel stable transgenic lines that were generated using the highly efficient Tol2 system, commonly used to generate transgenic zebrafish. A stable transgenic line consisting of the zebrafish ubiquitin promoter fused to eGFP expressed eGFP ubiquitously throughout development in a surface population of Astyanax. To define specific cell-types, we injected fish with a Cntnap2-mCherry construct that labels lateral line mechanosensory neurons in zebrafish. Strikingly, both constructs appear to label the predicted cell types, suggesting many genetic tools and defined promoter regions in zebrafish are directly transferrable to cavefish. The lines provide proof-of-principle for the application of Tol2 transgenic technology in A. mexicanus. Expansion on these initial transgenic lines will provide a platform to address broadly important problems in the quest to bridge the genotype to phenotype gap.

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Section: Discussionmentioning

confidence: 99%

“…To date, only one stable transgenic line has been published that was generated using the I-SceImeganuclease system [22]. A few studies have used Tol2 technology, commonly used to generate transgenic zebrafish, but analysis was limited to mosaic F0 fish [6,22], therefore, procedures for generating stable transgenic lines are unclear.…”

mentioning

confidence: 99%

Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system

Stahl

Peuß

McDole

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The identification of these circuits allows for cell‐autonomous manipulation of gene function, or optogenetic manipulation of behaviorally relevant neurons. In A. mexicanus , several genes have been implicated in behavior including Mc4r in feeding, hypocretin in sleep, and monoaminergic signaling in aggression . While presumably the neurons expressing these genes are implicated in behavior, a lack of transgenic accessibility represents a fundamental impediment to mechanistic investigation.…”

Section: Discussionmentioning

confidence: 99%

“…In A. mexicanus, several genes have been implicated in behavior including Mc4r in feeding, hypocretin in sleep, and monoaminergic signaling in aggression. 3,37,38 While presumably the neurons expressing these genes are implicated in behavior, a lack of transgenic accessibility represents a fundamental impediment to mechanistic investigation. The proof-of-principle of efficient implementation of Tol2 transgenesis in A. mexicanus should allow for the implementation of binary transgenic expression systems commonly used in other genetic model systems including GAL4/UAS and QF/QUAS systems.…”

Section: Discussionmentioning

confidence: 99%

“…The Mexican tetra Astyanax mexicanus is a versatile model system, which is well suited for the study of the evolution of morphology, behavior, and physiology . The different ecologies of the river and cave habitats of this species have led to the evolution of river dwelling and cave adapted populations which differ in a large number of traits (Figure A,B).…”

Section: Introductionmentioning

confidence: 99%

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Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system

Stahl

Peuß

McDole

et al. 2019

Developmental Dynamics

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Background Astyanax mexicanus is a well‐established fish model system for evolutionary and developmental biology research. These fish exist as surface forms that inhabit rivers and 30 different populations of cavefish. Despite important progress in the deployment of new technologies, deep mechanistic insights into the genetic basis of evolution, development, and behavior have been limited by a lack of transgenic lines commonly used in genetic model systems. Results Here, we expand the toolkit of transgenesis by characterizing two novel stable transgenic lines that were generated using the highly efficient Tol2 system, commonly used to generate transgenic zebrafish. A stable transgenic line consisting of the zebrafish ubiquitin promoter expresses enhanced green fluorescent protein ubiquitously throughout development in a surface population of Astyanax. To define specific cell‐types, a Cntnap2‐mCherry construct labels lateral line mechanosensory neurons in zebrafish. Strikingly, both constructs appear to label the predicted cell types, suggesting many genetic tools and defined promoter regions in zebrafish are directly transferrable to cavefish. Conclusion The lines provide proof‐of‐principle for the application of Tol2 transgenic technology in A. mexicanus. Expansion on these initial transgenic lines will provide a platform to address broadly important problems in the quest to bridge the genotype‐phenotype gap.

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Subterranean life: Behavior, metabolic, and some other adaptations of Astyanax cavefish

et al. 2020

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The ability of fishes to adapt to any aquatic environment seems limitless. It is enthralling how new species keep appearing at the deep sea or in subterranean environments. There are close to 230 known species of cavefishes, still today the best-known cavefish is Astyanax mexicanus, a Characid that has become a model organism, and has been studied and scrutinized since 1936. There are two morphotypes for A. mexicanus, a surface fish and a cavefish. The surface fish lives in central and northeastern Mexico and south of the United States, while the cavefish is endemic to the "Sierra del Abra-Tanchipa region" in northeast Mexico. The extensive genetic and genomic analysis depicts a complex origin for Astyanax cavefish, with multiple cave invasions and persistent gene flow among cave populations. The surface founder population prevails in the same region where the caves are. In this review, we focus on both morphotype's main morphological and physiological differences, but mainly in recent discoveries about behavioral and metabolic adaptations for subterranean life. These traits may not be as obvious as the troglomorphic characteristics, but are key to understand how Astyanax cavefish thrives in this environment of perpetual darkness.

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Hypocretin underlies the evolution of sleep loss in the Mexican cavefish

Cited by 28 publications

References 64 publications

Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system

Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system

Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system

Subterranean life: Behavior, metabolic, and some other adaptations of Astyanax cavefish

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