The goal of our current research is to understand how motor circuits generating body movements develop and mature, and apply the knowledge to protect them from aging and disease. To achieve this goal, we primarily study the motor systems of zebrafish because they allow access to motor circuits at the behavioral, cellular and genetic/molecular levels in the living animal.
Basic organization of the motor system
A comprehensive understanding of how the nervous system generates behavior depends in large part on knowing how the system is organized. Among the major challenges which remain is the identification of the functional neural circuits that produce measurable behavioral outputs from the diverse anatomical data and also the genetic programs that assemble these circuits. To achieve this end, we develop methods for visualizing and manipulating functional motor circuits as well as analyzing the gene functions that allow motor circuits to operate (Asakawa et al., PNAS 2008,Asakawa et al., Front Neural Circuits 2013). Key words: Transgenic, Gal4/UAS, BAC transgegesis
Development of motor system
Diverse movements of our body are regulated by motor neurons aligned in the brainstem and spinal cord that connect with cranial and skeletal muscles, respectively. Developing motor neurons with similar functions cluster together into discrete nuclei or columns, and collectively projected onto peripheral target muscles often in a topographic manner. We address cellular and molecular mechanisms underlying motor nucleus/column organizations and their faithful projections to target muscles (Asakawa and Kawakami, Cell Reports 2018). Key words: Cell size, Protocadherin, Brazil nut effect
Disease of motor system
Amyotrophic lateral sclerosis (ALS) is a neurological disorder in which the upper and lower motor neurons progressively degenerate, leading to muscular atrophy and eventually fatal paralysis. We address when and how healthy motor neurons begin to become abnormal and pathological in ALS by combining genetics, in vivo cell biology and systems biology of the crystal clear zebrafish neuromuscular system. Primary focus is on RNA-binding proteins that maintain physiological homeostasis of motor neurons (Asakawa et al., Nat Commun 2020). Key words: ALS, TDP-43, Optogenetics, Phase separation/transition
