Genes controlling and mediating locomotion behavior of the zebrafish embryo and larva

Abstract

Zebrafish embryos and larvae have stage-specific patterns of motility or locomotion. Two embryonic structures accomplish this behavior: the central nervous system (CNS) and skeletal muscles. To identify genes that are functionally involved in mediating and controlling different patterns of embryonic and larval motility, we included a simple touch response test in our zebrafish large-scale genetic screen. In total we identified 166 mutants with specific defects in embryonic motility. These mutants fall into 14 phenotypically distinct groups comprising at least 48 genes. Here we describe the various phenotypic groups including mutants with no or reduced motility, mechanosensory defective mutants, ‘spastic’ mutants, circling mutants and motor circuit defective mutants. In 63 mutants, defining 18 genes, striation of somitic muscles is reduced. Phenotypic analysis provides evidence that these 18 genes have distinct and consecutive functions during somitic muscle development. The genes sloth (slo) and frozen (fro) already act during myoblast differentiation, while 13 genes appear to function later, in the formation of myofibers and the organization of sarcomeres. Mutations in four other genes result in muscle-specific degeneration. 103 mutations, defining at least 30 genes, cause no obvious defects in muscle formation and may instead affect neuronal development. Analysis of the behavioral defects suggests that these genes participate in the diverse locomotion patterns observed, such as touch response, rhythmic tail movements, equilibrium control, or that they simply confer general motility to the animal. In some of these mutants specific defects in the developing nervous system are detected. Mutations in two genes, nevermind (nev) and macho (mao), affect axonal projection in the optic tectum, whereas axon formation and elongation of motorneurons are disrupted by mutations in the diwanka (diw) and the unplugged (unp) genes.

PDE10A Inhibition Reduces the Manifestation of Pathology in DMD Zebrafish and Represses the Genetic Modifier PITPNA

“… 50 , 51 , 52 The light-dark locomotor assay creates a pattern of stress-induced movements in the dark for a short period of time, followed by a resting state in the light, and it has been used in high-throughput screening of various neuroactive drugs. 50 , 51 , 52 Absence of dystrophin is known to reduce locomotion in sapje larvae; 29 , 35 however, it has never been analyzed and quantified in dystrophin-deficient sapje-like . Using an automatic system (DanioVision, Noldus), the locomotor activity between sapje-like and WT siblings at 5 dpf was clearly distinct.…”

“…This phenotype is first observable on day 4 after fertilization by using a non-lethal optical technique based on the transparency of zebrafish larvae and the birefringence properties of zebrafish skeletal muscle. 35 , 36 , 37 , 38 Previous work from our laboratory took advantage of dystrophin-deficient zebrafish to perform phenotypic high-throughput small-molecule screening that would not be possible in mammalian systems, and we identified compounds that restore muscle integrity as seen by birefringence and improved survival. 39 , 40 , 41 Other laboratories have also been utilizing this assay to identify small molecules that may yield promising DMD therapies, 42 , 43 , 44 since some have been confirmed in DMD mouse models 41 , 43 , 45 or used in clinical trials.…”

Pharmacogenetic and whole-brain activity analyses uncover integration of distinct molecular and circuit programs that drive learning

“…Subtracted image series were tracked using FLOTE software as previously described 7,8 . In the case of Strychnine-treated larvae, the previously described “accordion-like” shape 41 of the SLC response precluded acceptable tracking via FLOTE. Therefore, behavioral responses were manually scored blind to genotype as SLCs or No-Response by isolating the 17ms of video following the delivery of the acoustic pulse, and scoring body bends within this interval as SLCs.…”

Functional Analysis of Zebrafish socs4a: Impacts on the Notochord and Sensory Function

“…As required, F-actin was visualized by the staining of fixed embryos with phalloidin, as described [ 13 ], and neuromasts using MitoTracker Red CMX Ros (Invitrogen), as described [ 14 ]. To measure touch sensitivity and response, embryos were subjected to a light touch with a fine stimulus, just posterior to their otic vesicle [ 15 ], or alternatively subjected to light tapping of the Petri dish.…”