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Topic Name: New light on the underlying mechanism for abnormal development of the neural system
Category: Nanobiotechnology
Research persons: Prof. JING Naihe with co-workers from Japan, UK and US, CAS biochemists
Location: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), China
Details
Teaming up with co-workers from Japan, UK and
US, CAS biochemists have revealed a novel mechanism for maintaining neural stem
cells in early embryos. Their work was published in the 6 August issue of
Cell Development.
Neural stem cells (NSCs) are a type of stem cells that resides in embryonic
and adult neural systems with the capacity of self-renewal and differentiation.
They can give rise to new nerve cells (called neurons) and other cells that
support nerve cells (called glia), forming a complete central neural system
(CNS).
Previous studies have shown that the maintenance of the NSC pool is
essential for normal neural development. Precocious neurogenesis could reduce
the number of neurons and lead to a lack of glial types, impeding the normal
development of the central neural system. Although progress has been made in
identifying some components of the genetic program involved in regulating NSC
maintenance, the detailed underlying mechanisms still remain largely unknown.
During studies of the neural development of chick and mouse embryos, a
research team led by Prof. JING Naihe from the Institute of Biochemistry and
Cell Biology, found that both Id, the dominant negative regulators of proneural
proteins, and Hes1, one of the basic helix-loop-helix transcription factors that
regulate mammalian CNS development genes, are highly expressed in an embryo's
early neural tubes where NSC are concentrated. However, Ids are expressed prior
to proneural genes and share an overlapping expression pattern with Hes1.
Overexpression of Id2 in the chick hindbrain upregulates Hes1 expression and
inhibits proneural gene expression and neuronal differentiation. By contrast,
Hes1 expression decreases, proneural gene expression expands, and neurogenesis
occurs precociously in the Id expression inhibited chick and mouse embryos.
Mechanistic studies show that Id proteins interact directly with Hes1 and
release the negative feedback autoregulation of Hes1 without interfering with
its ability to affect other target genes. These results indicate that Id
proteins participate in NSC maintenance through sustaining Hes1 expression in
early embryos. Taken together, these results strongly support the notion that
sustained Hes1 expression by Id proteins is a critical mechanism for maintenance
of the NSC pool in early embryos.
Scientists say that the discovery will not only shed new light on the
underlying mechanism for abnormal development of the neural system, but also lay
an important basis for the studies of bran tumor treatment and prevention, as
well as stem cell therapy as Id is known for driving the growth of cancer.
About The Researcher:
Prof. JING Naihe
Naihe JING, professor and group leader of Institute
of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences,
Chinese Academy of Sciences (CAS). In 1988, Dr. Jing got his Ph. D. degree in
the Shanghai Institute of Biochemistry, CAS by working on peptide and protein
chemistry. Being a postdoctoral fellow, Dr. Jing began to work on developmental
neurobiology and cell biology in Laboratory of Cell Biology, Tsukuba Life
Science Center, The Institute of
Physical and
Chemical
Research, Japan. There Dr. Jing helped to set up a primary culture system of
neuroepithelial cells of day 10 mouse embryos. Then he found a human
teratocarcinoma cell line, PA-1, secreted the growth factors related to EGF and
IGF-I. After coming back to Shanghai in 1991, he have set up his own research
group to continue the work of developmental neurobiology. Dr. Jing¡¯s research
interest is the molecular mechanism of the development of central nervous system
(CNS) in mouse. After 4 years hard work, their group has finally cloned mouse
nestin gene, an intermediate filament protein expressed specifically in neural
precursor cell during CNS development. By immunochemistry and in situ
hybridization, they found this gene¡¯s specific expression pattern during mouse
eye and lens development. Using mouse embryonic carcinoma P19 cell¡¯s neuronal
differentiation as an in vitro model system, they found that stable-transfected
cell lines which are over-express Wnt-1 or N-cadherin gene could differentiate
into neuron-like cells without RA induction. Besides the works mentioned above,
Dr. Jing has worked as a visiting scientist in Dr. Francois Guillemot's
laboratory in Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC),
France with the project: Isolation of genes differentially expressed in
wild-type and HES1 mutant mouse embryos by Representational Difference
Analysis of cDNA in 1995. From 1996-1997, as a visiting scholar with sabbatical
leave, he was in Prof. Peter Gruss's lab in Max-Planck Institute of Biophysical
Chemistry, Goettingen, Germany, mainly working on eye specific cis-element
analysis of mouse Six3 gene using transgenic technology. In 2000, Dr. Jing also
worked as the visiting professor in Kumamoto University, Japan for three months.
In The Images-
1.Dr. Jing
2.neural development process
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