Zebrafish expression reporters and mutants reveal that the IgSF cell adhesion molecule Dscamb is required for feeding and survival

Abstract

Down syndrome cell adhesion molecules (DSCAMs) are broadly expressed in nervous systems and play conserved roles in programmed cell death, neuronal migration, axon guidance, neurite branching and spacing, and synaptic targeting. However, DSCAMs appear to have distinct functions in different vertebrate animals, and little is known about their functions outside the retina. We leveraged the genetic tractability and optical accessibility of larval zebrafish to investigate the expression and function of a DSCAM family member, dscamb. Using targeted genome editing to create transgenic reporters and loss-of-function mutant alleles, we discovered that dscamb is expressed broadly throughout the brain, spinal cord, and peripheral nervous system, but is not required for overall structural organization of the brain. Despite the absence of obvious anatomical defects, homozygous dscamb mutants were deficient in their ability to ingest food and rarely survived to adulthood. Thus, we have discovered a novel function for dscamb in feeding behavior. The mutant and transgenic lines generated in these studies will provide valuable tools for identifying the molecular and cellular bases of these behaviors.

Keywords:

• Zebrafish
• Dscam
• expression pattern
• genome editing
• feeding
• behavior

Acknowledgements

We thank Shin-Ichi Higashijima for the enhancer trap donor plasmid (pBluescript-Gbait-Hsp-Gal4ff-BGHpA), Koichi Kawakami for the Tg(UAS:GFP) line, Anand Chandrasekhar for the Tg(isl1:GFP) line, Gage Crump for the Tg(UAS:KikGR) line, Robert Modlin for the Tg(nbt:DsRed) line, and Kate Whitlock for advice on olfactory analyses. Anti-Hermes and 5E11 antibodies were generously donated by James Fadool and Malgorzata Kloc, respectively. We thank Marianne Cilluffo of the UCLA Brain Research Institute Electron Microscopy Core Facility for histological processing of larvae for TEM. We also thank Mark Frye for the LED array for OMR analyses. Inspiration for these studies came from preliminary investigations conducted by Fang Wang. DPJ was supported by a scholarship from the Achievement Rewards for College Scientists (ARCS) Foundation and the UCLA Philip Whitcome Predoctoral Training Program in Molecular Biology.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by a grant to AS from the National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR064582].