The goal of our current research is to understand how neural circuits generating body movements develop and become mature, and apply the knowledge to protecting 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.

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

Dissection 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: Transgenic, Gal4/UAS, BAC transgegesis

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


Relevant publications

  • Kamezaki A, Sato F, Aoki K, Asakawa K, Kawakami K, Matsuzaki F, Sehara-Fujisawa A. (2016). Visualization of Neuregulin 1 ectodomain shedding reveals its local processing in vitro and in vivo. Scientific Reports 6:28873.
  • Takeuchi M, Matsuda K, Yamaguchi S, Asakawa K, Miyasaka N, Lal P, Yoshihara Y, Koga A, Kawakami K, Shimizu T, Hibi M. (2015). Establishment of Gal4 transgenic zebrafish lines for analysis of development of cerebellar neural circuitry. Developmental Biology 397:1-17.
  • Kwon HB, Fukuhara S, Asakawa K, Ando K, Kashiwada T, Kawakami K, Hibi M, Kwon YG, Kim KW, Alitalo K, Mochizuki N. (2013). The parallel growth of motoneuron axons with the dorsal aorta depends on Vegfc/Vegfr3 signaling in zebrafish. Development 140:4081-4090.
  • Asakawa K*, Gembu A and Kawakami K*. (2013). Cellular dissection of the spinal cord motor column by BAC transgenesis and gene trapping in zebrafish. Frontiers in Neural Circuits (*Co-correspondence)
  • Asakawa K, Higashijima S, and Kawakami K. (2012). An mnr2b/hlxb9lb enhancer trap line that labels spinal and abducens motor neurons in zebrafish. Developmental Dynamics 241, 327-332.
  • Asakawa K, Kawakami K. (2010). A transgenic zebrafish for monitoring in vivo microtubule structures. Developmental Dynamics 239, 2695-2699.
  • Asakawa K and Kawakami K. (2009) The Tol2-mediated Gal4-UAS method for gene and enhancer trapping in zebrafish. Methods 49:275-281.
  • Asakawa K, Suster ML, Mizusawa K, Nagayoshi S, Kotani T, Urasaki A, Kishimoto Y, Hibi M and Kawakami K. (2008). Genetic dissection of neural circuits by Tol2 transposon-mediated Gal4 gene and enhancer trapping in zebrafish. Proc Natl Acad Sci U S A 105:1255-1260.

Funding sources

科研費補助金

  • 2019-21年度 科研費 基盤研究(C)(代表)
  • 2016-18年度 科研費 基盤研究(C)(代表)
  • 2013-15年度 科研費 若手研究(B)(代表)
  • 2011-12年度 科研費  新学術領域研究 公募 (代表)
  • 2010-12年度 科研費 若手研究(B)(代表)
  • 2006-08年度 学振・特別研究員奨励費(代表) 

助成金

  • 2020年 国立遺伝学研究所共同研究「NIG-JOINT」共同研究(B)
  • 2018年 加藤記念難病研究助成基金 研究助成
  • 2018年 せりか基金 研究助成金
  • 2016年 公益財団法人 日本科学協会: 海外発表促進助成金
  • 2014年 公益信託「生命の彩」ALS研究助成基金助成金
  • 2013年 公益財団法人 武田科学振興財団 医学系研究奨励
  • 2013年 ノバルティス科学振興財団(ノバルティス研究奨励金)
  • 2012年 第一三共生命科学研究振興財団(第30回研究助成)
  • 2012年 住友財団(基礎科学研究助成)
  • 2011年 総研大学融合推進センター(若手研究者研究支援事業)
  • 2011年 三菱財団(自然科学研究助成)
  • 2010年 総研大学融合推進センター(若手研究者研究支援事業)
  • 2010年 花王芸術・科学財団(科学技術研究助成)
  • 2009年 上原記念生命科学財団(研究奨励金)
  • 2005年 日本科学協会(笹川科学研究助成)