FY2016 Annual Report

Formation and Regulation of Neuronal Connectivity Unit

Visiting Professor David Van Vactor



We wish to understand the conserved mechanisms that underlie the formation and maintenance of synaptic connections in the nervous system. Decades of research defining hundreds of effector genes required for formation and maintenance of the Drosophila neuromuscular junction (NMJ) has made this system ideal to define upstream regulatory mechanisms that deploy gene networks in order to tune synapse form, function and plasticity. We are particularly interested in post-transcriptional strategies, and have focused on RNA processing and microRNA machinery. As part of our research mission, we also support the OIST Drosophila genetics core facility in order to make these resources accessible to all other OIST units. Finally, a key part of our unit’s mission at OIST is to create and support international educational workshops to enhance training and expand the community of young scientists who value OIST and its unique strengths. This educational mission expanded in 2015 to include innovative undergraduate curriculum, in addition to primary education at the pre-college level.

1. Staff

  • Dr. David Van Vactor, Professor
  • Dr. Takakazu Yokokura, Group Leader (Project 1 & Drosophila Core)
  • Dr. Cecilia Lu, Group Leader (Project 2)
  • Ms. Seiko Yoshikawa, Technician
  • Thi Thu Van Dinh, Technician
  • Ms. Kun Xiao, Technician
  • Dr. Deena Vardhini Yeraguntla, Technician (- Sept., 2016)
  • Ms. Victoria Hamlin, Visiting Researcher (- August, 2016)
  • Ms. Lauren Dembeck, Postdoctoral fellow (August, 2016 -)
  • Ms. Shino Fibbs, Research Unit Administrator (- June, 2016)
  • Ms. Yuki Nakagawa, Research Unit Administrator (July, 2016-)

2. Collaborations

  • Theme: Computational analysis of RNA splicing patterns in high-content RNAseq datasets, and conservation of RNA splicing and stability effects from Drosophila to human models of Spinal Muscular Atrophy (SMA).
    • Type of collaboration: Joint research
    • Researchers: Dr. Margarida Gama-Carvalho (University of Lisbon, Lisbon, Portugal)
  • Theme: Defining patterns of RNA splicing and stability characteristic of human IPS-derived mixed motor neuron model of Spinal Muscular Atrophy (SMA).
    • Type of collaboration: Joint research
    • Researchers: Dr. Lee Rubin (Dept. of Stem Cell and Regenerative Biology, Harvard University, Boston, MA, USA)
  • Theme: MicroRNA Modulators of Premotor Interneuron to Motor Neuron Connectivity in Drosophila.
    • Type of collaboration: Joint research
    • Researchers: Drs. Hiroshi Kohsaka and Akinao Nose (University of Tokyo, Tokyo, Japan).
  • Theme: Glial-Neuronal Interactions that Contribute to Motor Axon integrity in Drosophila.
    • Type of collaboration: Joint research
    • Researchers: Drs. Christian Klambt (University of Muenster, Muenster, Germany).

3. Activities and Findings

3.1 Spinal Muscular Atrophy (SMA)

Having defined conserved target genes downstream of SMN-family proteins in fly and human, we are now in the process of determining the cellular site of action and the synaptic functions for these prioritized pathways. Our unpublished data suggest that axon-ensheathing glial cells may play an unexpected role in SMN-dependent motor neuron pathology, and we are examining the potential contribution of secreted factors to this anticipated support relationship. In parallel, having discovered that cytoskeletal protein networks represent a predominant class of Smn target genes, we are examining the synaptic functions of conserved targets such as the spectroplakin Short-stop (Shot). Generation of antibody reagents is currently underway to test the function and localization of this and other Smn-dependent genes and protein isoforms.

3.2 Micro RNA Regulation of Synaptic Adhesion Molecules

In parallel with our efforts to profile motor neurons and pre-motor interneurons to define microRNAs required for CNS synaptogenesis, we have also collaborated with Drs. Hiroshi Kohsaka and Akinao Nose at the University of Tokyo to examine synaptic phenotypes for several microRNAs that were identified in our Harvard-based screens of NMJ morphogenesis defects. A key part of this project is to use developmental analysis to define the early stages of inhibitory glutamatergic premotor PMSI neuron innervation of motor neurons during the late stages of embryogenesis. 


4. Publications

4.1 Journals

Van Vactor, D. and Sigrist, S.J. (2017) Current Opinion in Neurobiology, invited review article, in press.

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations
  1. Lu CS., Understanding microRNA codes in the development of neural connectivity, OIST Internal Seminar, Okinawa, Japan, March 11, 2016
  2. Van Vactor, D. “The Regulation of Synapse Morphogenesis and Plasticity”: Developmental Neurobiology Course (DNC) Lecture, July 29, 2016.
  3. Van Vactor, D.  “Introduction to the Form and Function of the Neuron: Visualization and Analysis of Neuronal Cell Biology” : OIST Collaborative International Undergraduate Workshop (CIUW) Lecture, August 2, 2016.

5. Intellectual Property Rights and Other Specific Achievements

  • Incentive Program-Support for KAKENHI grant applications

6. Meetings and Events

6.1 Developmental Neurobiology Course 2016
  • Date: July
  • Venue: OIST Campus
  • Co-organizers: Drs. Ichiro Masai, Tomomi Shimogori, David Van Vactor, and Yoko Yazaki-Sugiyama
  • Speakers:
    • Dr. Rosalind Segal (Harvard Medical School)
    • Dr. Yimin Zhou (UCSD)
    • Dr. Su Guo (UCSF)
    • Dr. Takaki Miyata (Nagoya University)
    • Dr. Hisashi Umemori (Children’s Hospital, Boston)
    • Dr. Tomomi Shimogori (RIKEN BSI)
    • Dr. David Van Vactor (Harvard Medical School/OIST)
    • Dr. Hiroshi Kohsaka (University of Tokyo) 
    • Dr. Thomas Clandinin (Stanford University)
    • Dr. Yoko Yazaki-Sugiyama (OIST)
    • Dr. Minoru Saito (Tokyo Metropolitan Institute of Medicine)
    • Dr. Naoshige Uchida (Harvard University)
    • Dr. Nirao Shah (UCSF)
    • Dr. Atsushi Miyawaki (RIKEN BSI)
    • Dr. Herwig Baier (Max Planck Institute of Neurobiology)
    • Dr. Ichiro Masai (OIST)
    • Dr. Tsuyoshi Miyakawa (Fujita Health University)
    • Dr. Takako Mornimoto (TUPL)


6.2 Collaborative International Undergraduate Workshop 2016
  • Title: Quantitative Analysis of Behavior & Neurobiology
  • Date: August 1 - August 7, 2016
  • Venue: OIST Campus
  • Co-organizers: Drs. David Van Vactor, Mahesh Bandi and Jeff Wickens

This international undergraduate workshop is designed to present students with a range of major research topics in the neurosciences, from organismal to molecular resolution.  By combining scientific research presentations, foundational lectures, hands-on data collection and quantitative skills workshops, this one-week intensive course will provide opportunities for students to explore cutting edge questions.  Team problem-solving and analysis with statistical and computational tools will be used to deepen collaborative connections while demonstrating fundamentals of experimental design and data interpretation.


OIST Instructors:

Lecturer team:

David Van Vactor, Ph.D.  (Visiting Professor, OIST; Professor, Harvard Medical School) [Lecturer]

Jeffrey Wickens, Ph.D. (Dean of Graduate Program; Professor, OIST) [Lecturer]

Greg Stephens (Adjunct Professor, OIST; Profesor, Vrije Universiteit Amsterdam) [Lecturer]


Visiting/Collaborating Faculty Instructors:

Lecturer team:

Thomas Clandinin, Ph.D. (Professor, Neurobiology, Stanford University School of Medicine) [Contact for visiting undergraduates from Stanford University; Course Instructor]

Takashi Suzuki, Ph.D. (Professor, Tokyo Institute of Technology) [Course coordination with Tokyo Institute of Technology students; Course Instructor]

Karl Johnson, Ph.D. (Professor and Chairman, Department of Neuroscience, Pomona College) [Contact for visiting undergraduates from Pomona and Claremont Colleges; Course Instructor and Challenge Lab Leader]

Tsuyoshi Mizoguchi, Ph.D. (Professor, International Christian University) [Contact for visiting undergraduates from ICU; Course Instructor]


Workshop and Curriculum Development team:

Melanie Stefan, Ph.D. (Lecturer, University of Edinburgh) [Computational modeling of neural circuits workshop; discussion facilitator & assessments]

Elizabeth McNeill, Ph.D. (Instructor in Cell Biology, Harvard Medical School) [Statistics and quantitative analysis workshop; discussion facilitator & assessments]

Yan Liu, Ph.D. (Curriculum Fellow & Lecturer, Harvard Medical School) [Consulting  Assessment Specialist and Analyst]


Mentoring & Career Development team:

Rachel Brennan (Professional Development; OIST Graduate School) [Career Panelist]

Jason Heustis (Curriculum Fellow, Harvard Medical School, Boston, MA) [Pedagogy Specialist, Instructor & Career Panelist]

Mary Lothrop (Director of Health Professions & STEM Advising, Middlebury College, VT) [Career Panelist]


Student recruitment and follow up advising (not part of visiting team):

Akinao Nose, Ph.D.  (Professor, Physics, University of Tokyo) [Course coordination with University of Tokyo physics faculty and students]

Takao Hensch, Ph.D. (Professor, Molecular and Cellular Biology, Harvard University) [Symposium Organization; contact for visiting undergraduates from Harvard; coordination/liaison with RIKEN BSI faculty; Course Instructor]


OIST Curriculum Specialist:

Jeremie Gillet, Ph.D.  (Postdoctoral Teaching Fellow, OIST Graduate School) [Computational Solutions to Statistical and Other Quantitative Analytical Challenges]


Teaching Assistants:


Helen Yang (returning senior/head TA; Stanford University)

Lauren Kershberg (TA; Pomona College/Harvard University)


OIST Graduate School Staff (Planning/Organization/Logistics/Support & Financial):

Harry Wilson

Kozue Higashionna

Yuuki Guzman

Keely Brandon

Kanako Aono

Takashi Ihara

Shiho Uezu





This special workshop will provide an opportunity to achieve several goals:

(1) To illustrate interdisciplinary research approaches and interfaces that propel scientific discovery (current focus of neuroscience).

(2) To design integrated lecture and practical activities that present paradigms in experimental design and analysis.

(3) To introduce rigorous quantitative methods and strategies for advanced data analysis.

(4) To create a cross-cultural experience intended to promote international collaboration at an early stage prior to graduate training.

(5) To promote team-based problem-solving strategies.

(6) To help students model graduate level education and research activities in an English-speaking environment, through mentorship and active career advising.

(7) To showcase the special mission and strengths of OIST as a platform for international scholarship and research.


7. Other

Nothing to report.