Skip to content

Menu
  • USC Stem Cell
  • About
    • Stem Cell FAQs
    • Mission and History
    • California’s Leadership in Stem Cell Research
    • Founding Supporters and Ambassadors
    • Well-being
    • Jobs
  • News & Events
    • News
    • Events
    • Videos
    • Impact Reports and Newsletters
  • Research
    • Department Faculty
    • Eli and Edythe Broad Center Faculty
    • Research Facilities
    • Clinical Translation
    • USC+CHLA Alpha Clinic
    • Translational Research Committee
    • USC Stem Cell Research Oversight Committee (SCRO)
    • Apply to Become Center Faculty
  • Education & Training
    • Undergraduate
    • Master’s Program
    • PhD Program
    • Medical Education
    • Postdoctoral Opportunities
    • Our Trainees
  • Funding
  • Inclusive Excellence
  • Support Us
  • Contact
    • Directory
    • Subscribe
  • Search

Ostrow researcher probes the roots of microcephaly, inside cells

By  Katharine Gammon

Posted September 6, 2019
Reading Time 3 minutes

in this section

  • News
  • Events
  • Videos
  • Impact Reports and Newsletters

read this next

Jianfu Chen (Photo courtesy of the Ostrow School of Dentistry of USC)

A Zika surprise: African strain can do more damage than Asian strain

  • Follow us on
  • Like us on
  • Follow us on
  • Follow us on
Assistant Professor Jianfu Chen is working on ways to understand how the disorder is regulated in genes, and hopes one day to find treatments.
Assistant Professor Jianfu Chen is working on ways to understand how the disorder is regulated in genes, and hopes one day to find treatments.

Microcephaly is a condition where the circumference of an individual’s head is smaller than normal. It can be caused by genetic abnormalities as well as fetal exposure to drugs; alcohol; certain viruses, such as Zika virus; or toxins during pregnancy.

It’s rare — there are fewer than 200,000 cases a year in the United States. Assistant Professor Jianfu “Jeff” Chen aims to better understand the mechanisms that cause microcephaly — in particular, the ways in which specific genetic mutations create this condition.

Chen has been interested for the past few years in better understanding how the disorder develops. “Often times, patients with microcephaly also have intellectual disability, but the cause of the smaller brain size remains to be established,” he said.

In 2014, Chen created a mouse model for microcephaly — but found that the difference between a microcephalic mouse brain and a regular mouse brain wasn’t a large one. “Using the mouse model, we thought we were missing some component that was specific to human brains,” he said.

Tiny, artificial brains

In a new paper published in Nature Communications, Chen adopted a new model system: a brain organoid. Brain organoids are artificially-grown miniature organs that resemble the brain, created by culturing human pluripotent stem cells in a three-dimensional bioreactor and developed over months. “We can create three-dimensional brain tissue to model early human brain development,” Chen explained.

Using this system, he was able to tease out the dramatic size difference in a brain when a specific gene — WDR62 — is knocked out. “Basically, we discovered a new mechanism to explain why microcephaly develops,” he said. The mutation of this gene changes many things — including how many tiny hairs, called cilia, are produced in the brain cells — and how long they are.

“Because you have too many cilia and they stay longer than they’re supposed to, the cell cycle is delayed,” Chen explained. This delay causes less cell division and leads to the production of fewer neurons, which contributes to a smaller brain size in patients.

Why is the disorder often accompanied with intellectual disability?

Chen’s next step is to understand why microcephaly is often accompanied with intellectual disability. Most children born with microcephaly have intellectual disability, but not all. “We are trying to understand how that happens: why the mutation of certain genes leads to behavior disorder,” Chen said. He hopes to connect the particular quirk of cilia dysregulation to intellectual disability.

His ultimate goal is to understand the cause of this microcephaly disease and identify potential set of treatments. One possibility for the future is to focus strategies on a downstream mediator, which can reduce cilia length and numbers.

Using the brain organoid lets the researchers understand brain development on a whole new level — showing the process in far more detail than mouse models. “This work is important because, for the first time, we can model this WDR62-related human brain disorder in a culture dish and discover some novel disease causes that cannot be easily identified in mouse models,” Chen said.

Read more about: Musculoskeletal
Mentioned in this article: Jianfu Chen, PhD

Post navigation

← USC Stem Cell scientist Thomas Lozito looks to lizards in hopes of healing humans
USC scientists surmount big obstacle to reprogram cells →
Keck School of Medicine of USC
1975 Zonal Ave.
Los Angeles, CA 90033
Google Map
Phone: (323) 442-1900
Hours:
Monday–Friday
7:30am–5:00pm PST
Resources For
  • Current Students
  • Faculty & Staff
  • Patients
  • Community
  • Press
  • Visitors
Areas of Focus
  • Education & Training
  • Research
  • Patient Care
  • Community
Departments and Offices
  • Departments
  • Institutes and Centers
  • Research Programs
  • Administrative Offices
About Keck
  • History
  • Leadership
  • Annual Report
  • Digital Accessibility
Intranet
  • Privacy Notice
  • Notice of Non-Discrimination
  • Smoke-Free Policy

Copyright © 2025 University of Southern California

  • Research
    • Research HomeCutting-edge research drives innovation in healthcare at the Keck School of Medicine
    • Where Research Happens
    • Research Funding
    • Training and Education
    • Researcher Resources
    • Collaborate and Partner
  • Education
    • Education HomeNurturing future healthcare leaders through excellence in education
    • MD Program
    • Residencies and Clinical Fellowships
    • PhD Programs
    • Master’s Programs
    • Professional Programs
    • Post-Doctoral Researchers
    • CME, Certificate & Undergraduate Programs
  • Departments, Institutes & Centers
    • Basic Science and Clinical DepartmentsExploring foundational science and specialized clinical fields
    • Institutes and Centers
    • Research Programs
  • About
    • About the Keck SchoolDiscover the mission, history, and vision of the Keck School of Medicine
    • History
    • Leadership
    • Dean’s Corner
    • Life in Southern California
    • Visit
  • Our Faculty
  • Current Students
  • Newsroom
  • Events Calendar
  • Support the Keck School
  • USC.edu
  • Are you a Patient?