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私たちの研究の目標は、身体の動きを生み出す神経回路が、どのように発達して成熟するかを理解し、そこから得た知識をつかって、運動神経回路を加齢や疾患から保護することです。この目標を達成するために、主に熱帯魚ゼブラフィッシュの運動系を研究しています。ゼブラフィッシュでは、生きている動物の運動神経回路を、行動、回路、細胞、および遺伝子・分子レベルで研究できるからです。

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Organization of 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 measureable 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 (See Asakawa et al., PNAS 2008, Asakawa et al., Front Neural Circuits 2013). Key words: Motor neuron, Transgenic, Gal4/UAS, BAC transgegesis

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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. (See 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. (See Asakawa et al., Nat Commun 2020) Key words: TDP-43, Optogenetics, Phase separation

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