UCLA

The brain is composed of complex neuronal circuits that provide the physiological basis for our cognition, perception, and behavior. Unraveling how neurons establish these circuits and the myriad of molecular signals that guide their development is one of the most daunting tasks in neurobiology. Down Syndrome Cell Adhesion Molecules (DSCAMs) play an evolutionarily conserved role in regulating key aspects of neuronal wiring, including programmed cell death, neuronal migration, axon guidance, neurite branching, branch spacing, and synaptic targeting. However, despite being expressed broadly throughout the vertebrate nervous system, there remains a paucity of in vivo investigations of the functions of DSCAM family members across different regions of the brain. Additional studies could shed light on how well DSCAM functions are conserved across the diversity of neuronal cells types in different neuronal systems.

In the present study, I leveraged the genetic tractability and optical accessibility of the larval zebrafish model to investigate the expression and function of a DSCAM family member, dscamb, throughout the developing brain. Using targeted mutagenesis, I created the first dscamb loss-of-function mutant lines, and through a combination of transgenic approaches, I provided the first characterization of dscamb expression. Using these genetic tools, I uncovered that, similar to DSCAM family members in other species, Dscamb is expressed broadly throughout the brain, spinal cord, and peripheral nervous system. However, I also identified several regions of expression, particularly in the peripheral nervous system and muscle cells, that have not been described for other DSCAM family members. Unlike other vertebrate DSCAMs, I found no evidence that Dscam is required for retinal development. Moreover, dscamb loss-of-function did not affect the overall structural organization of the brain and spinal cord. Despite an absence of apparent anatomical defects a series of behavioral analyses revealed that dscamb mutants are severely deficient in their ability to find or capture food, suggesting that this protein has a critical, and perhaps subtle, function in the wiring of neuronal systems that underlie feeding behavior.