SCIENTIFIC RELEASE
19 DECEMBER 2014
A*STAR SCIENTISTS DISCOVER GENE CRITICAL FOR PROPER BRAIN
DEVELOPMENT
This gene accounts for the size of the human brain and potentially our superior
cognitive abilities
Singapore—Scientists at A*STAR’s Institute of Medical Biology (IMB) and Institute
of Molecular and Cellular Biology (IMCB) have identified a genetic pathway that
accounts for the extraordinary size of the human brain. The team led by Dr Bruno
Reversade1 from A*STAR in Singapore, together with collaborators from Harvard
Medical School, have identified a gene, KATNB1, as an essential component in a
genetic pathway responsible for central nervous system development in humans and
other animals.
By sequencing the genome of individuals of normal height but with a very small head
size, the international team revealed that these individuals had mutations in the
KATNB1 gene, indicating that this gene is important for proper human brain
development. Microcephaly (literally meaning “small head” in Latin) is a condition
often associated with neurodevelopmental disorders. Measured at birth by
calculating the baby’s head circumference, a diagnosis of microcephaly is given if it
is smaller than average.
Microcephaly may stem from a variety of conditions that cause abnormal growth of
the brain during gestation or degenerative processes after birth, all resulting in a
small head circumference. In general, individuals with microcephaly have a reduced
life expectancy due to reduced brain function which is often associated with mental
retardation.
1 Dr. Bruno Reversade, a human geneticist and embryologist holds a Senior Principal Investigator position at IMB and IMCB.
He is the coordinating investigator on A*STAR’s strategic programme on Orphan Genetic Diseases. He is an adjunct professor
of the Department of Paediatrics at the National University of Singapore. He is also a Fellow of the Branco Weiss Foundation
based at ETH in Switzerland, and was the first recipient of the A*STAR Investigatorship, and the first EMBO Young Investigator
based outside Europe. For more information about Dr. Reversade’s laboratory, visit www.reversade.com.
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The team also carried out further experiments to determine the function of KATNB1,
whose exact mode of action was previously unknown in humans. Using organisms
specifically designed to lack this gene, they realised that KATNB1 is crucial for the
brain to reach its correct size. Zebrafish and mice embryos without this gene could
not live past a certain stage and showed dramatic reduction in brain and head size,
similar to the human patients. Their results were published in the 17 December 2014
online issue of Neuron, the most influential journal in the field of Neuroscience.
Sequencing and screening for this particular gene before birth or at birth might also
help to detect future neurocognitive problems in the general population. Dr
Reversade said, “We will continue to search for other genes important for brain
development as they may unlock some of the secrets explaining how we, humans,
have evolved such cognitive abilities.”
Prof Birgit Lane, Executive Director of IMB, said, “This is one of a small number of
genes that scientists have found to be vital for brain development. The work is
therefore an important advance in understanding the human brain. The team’s
findings provide a new platform from which to look further into whether - and how this gene can be used for targeted therapeutic applications.”
Prof Hong Wanjin, Executive Director of IMCB, said, “This coordinated effort shows
the increasingly collaborative nature of science. As the complexity and
interdisciplinary nature of research evolves, so do the networks of collaborations
between research institutes at A*STAR and across continents.”
_________________________________________________________________________
Notes for Editor:
The research findings described in this media release can be found in the 17
December online issue of Neuron, Cell Press under the title, “Katanin p80 Regulates
Human Cortical Development by Limiting Centriole and Cilia Number” by Wen F.
Hu,1,2,3,5,6 Oz Pomp,19 Tawfeg Ben-Omran,12 Andrew Kodani,18 Katrin Henke,4,9
Ganeshwaran H. Mochida,1,2,7,10 Timothy W. Yu,1,7,11 Mollie B. Woodworth,1,2,3,7
Carine Bonnard,19 Grace Selva Raj,19Thong Teck Tan,19 Hanan Hamamy,21 Amira
Masri,23 Mohammad Shboul,19 Muna Al Saffar,1,2,13 Jennifer N. Partlow,1,2,3
Mohammed Al-Dosari,17 Anas Alazami,14 Mohammed Alowain,15,16 Fowzan S.
Alkuraya,14,16 Jeremy F. Reiter,18 Matthew P. Harris,4,9,24,* Bruno Reversade,19,20,22,24
and Christopher A. Walsh1,2,3,5,6,7,8,24.
1
Division of Genetics and Genomics, Department of Medicine
2
Manton Center for Orphan Disease Research
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3
Howard Hughes Medical Institute
4
Department of Orthopedic Research
Boston Children’s Hospital, Boston, MA 02115, USA
5
Program in Neuroscience
6
Harvard MD-PhD MSTP Program
7
Department of Pediatrics
8
Department of Neurology
9
Department of Genetics
Harvard Medical School, Boston, MA 02115, USA
10
Pediatric Neurology Unit, Department of Neurology, Massachusetts General
Hospital, Boston, MA 02114, USA
11
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard
University, Cambridge, MA 02142, USA
12
Clinical and Metabolic Genetics Division, Department of Pediatrics, Hamad Medical
Corporation, Doha 3050, Qatar
13
Department of Pediatrics, Faculty of Medicine and Health Sciences, United Arab
Emirates University, Al-Ain, United Arab Emirates
14
Department of Genetics
15
Department of Medical Genetics
King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
16
Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University,
Riyadh 11533, Saudi Arabia
17
Department of Pharmacognosy, College of Pharmacy, King Saud University,
Riyadh 11451, Saudi Arabia
18
Department of Biochemistry and Biophysics, Cardiovascular Research Institute,
University of California, San Francisco, San Francisco,
CA 94158, USA
19
Institute of Medical Biology, Human Genetics and Embryology Laboratory
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20
Institute of Molecular and Cellular Biology, A*STAR, Singapore 138648, Singapore
21
Department of Genetic Medicine and Development, Geneva University, Geneva
1211, Switzerland
22
Department of Paediatrics, National University of Singapore, Singapore 119260,
Singapore
23
Department of Paediatrics, Faculty of Medicine, University of Jordan, Amman
11942, Jordan
*Correspondence
should
be
([email protected])
addressed
to:
Bruno
Reversade
_________________________________________________________________________
For media queries and clarifications, please contact:
Vithya Selvam (Ms)
Senior Officer, Corporate Communications
Agency for Science, Technology and Research
Tel: (+65) 6826 6291
Email: [email protected]
Tan Yun Yun (Ms)
Senior Officer, Corporate Communications
Agency for Science, Technology and Research
Tel: (+65) 6826 6273
Email: [email protected]
About A*STAR’s Institute of Medical Biology (IMB)
IMB is one of the Biomedical Sciences Institutes of the Agency for Science,
Technology and Research (A*STAR). It was formed in 2007, with a mission to study
mechanisms of human disease in order to discover new and effective therapeutic
strategies for improved quality of life.
IMB has 20 research teams working in three primary focus areas - stem cells,
genetic disease, and skin biology. The teams work closely with clinical collaborators
as well as industry partners, to target the challenging interface between basic
science and clinical medicine. IMB’s strategic research topics are targeted at
translational research to understand the mechanisms of human disease so as to
identify new strategies for disease amelioration, cure and eradication and to improve
health and wellbeing. Since 2011, IMB has also hosted the inter-research institute
Skin Biology Cluster platform, and leads major strategic funding programs in rare
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genetic diseases and in skin biology. In 2013 IMB became a founding institute of the
Skin Research Institute of Singapore.
For more information about IMB, please visit www.imb.a-star.edu.sg.
About A*STAR’s Institute of Molecular and Cell Biology (IMCB)
The Institute of Molecular and Cell Biology (IMCB) was established in 1987 at the
National University of Singapore (NUS) before becoming an autonomous research
institute (RI) of A*STAR and moving to Biopolis in 2004. IMCB strives to maintain the
scientific excellence of PI-driven research and at the same time aims to promote
collaborative team-based projects of medical and industrial relevance.
Funded primarily by the Biomedical Research Council (BMRC) of A*STAR, IMCB’s
research activities focus on four major fields: Animal Models of Development and
Disease, Cancer Genetics and Therapeutics, Cell Biology in Health and Disease,
and Structural Biology and Drug Discovery.
For more information about IMCB, please visit www.imcb.a-star.edu.sg
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead
public sector agency that fosters world-class scientific research and talent to drive
economic growth and transform Singapore into a vibrant knowledge-based and
innovation driven economy.
In line with its mission-oriented mandate, A*STAR spearheads research and
development in fields that are essential to growing Singapore’s manufacturing sector
and catalysing new growth industries. A*STAR supports these economic clusters by
providing intellectual, human and industrial capital to its partners in industry.
A*STAR oversees 18 biomedical sciences and physical sciences and engineering
research entities, located in Biopolis and Fusionopolis, as well as their vicinity. These
two R&D hubs house a bustling and diverse community of local and international
research scientists and engineers from A*STAR’s research entities as well as a
growing number of corporate laboratories.
For more information on A*STAR, please visit www.a-star.edu.sg
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