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Name |
Email |
Telephone |
| Professor |
KONDOH, Hisato, Ph.D. |
 |
+81-6-6879-7964 |
| Associate Prof. |
HIGASHI, Yujiro, Ph.D. |
 |
+81-6-6879-7964 |
| Associate Prof. |
KAMACHI, Yusuke, Ph.D. |
 |
+81-6-6879-7964 |
| Assistant Prof. |
UCHIKAWA, Masanori, Ph.D. |
 |
+81-6-6879-7964 |
| FAX |
+81-6-6877-1738 |
| Postal Mail Address |
Graduate School of Frontier
Biosciences, Osaka University
1-3 Yamadaoka, Suita, Osaka 565-0871, Japan |
This group investigates regulation of the
embryonic development, how intercellular signaling molecules
act, how cells respond to the signals and activate transcriptional
regulators, and how the action of transcriptional regulators
cause cell differentiation. The major subject of the research
is the differentiation of the primitive central nervous system
and the sensory organs exemplified by eye lens.
| 1 |
Induction of the central
nervous system and the sensory organ primordial from
the ectoderm. |
| Induction signals from nearby tissues activates
master transcriptional regulator genes, such as Sox2.
Investigation of the regulation of such genes will
reveal fundamental mechanisms of the induction of cell
differentiation. |
| Fig. 1 An enhancer of the Sox2
gene responding to the neural induction signal is activated
in the tissue area surrounding Hensen's node. |
|
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| 2 |
Molecular mechanisms
of differentiation of lens cells and neural primordium. |
| Multiple transcriptional regulators interact
in initiation and progression of cell differentiation
process. Lens cells and neural primordium share SOX2
as the major transcriptional regulator. Interaction
of SOX2 with other transcriptional regulators in differentiation
of these tissues is investigated. |
| Fig. 2-1 Neural plate, the neural
primordium, expresses Sox2. |
|
 |
| Fig. 2-2 Lens differentiation
initiates when Pax6 and Sox2 genes are
expressed together in the head ectoderm. |
|
 |
| 3 |
Molecular interactions
among SOX, Pax and POU transcriptional regulators
in cell differentiation. |
| Not a single transcriptional regulator but
molecular complexes of the regulators interact with
various regulatory DNA sequences and determine cell
states. Molecular mechanisms of the interaction and
of the transcriptional regulation are investigated. |
| Fig. 3. Pax6 and SOX2 form a
molecular complex and activate delta-crystallin enhancer. |
|
 |
| 4 |
Basic function of SOX
family regulators in cell differentiation. |
| SOX proteins interact with various partner
factors, and a combination of a SOX-partner pair selectively
activates a specific set of genes and determines cell
differentiation. |
| Fig. 4 Examples of SOX-partner
combinations in cell differentiation. |
|
 |
| 5 |
Role of ZFHX1 family
proteins in embryogenesis |
| The vertebrate ZFHX1 family consists of
the two closely related proteins, SIP1 (Smad-interacting
protein 1) and dEF1 (d-crystalline enhancer factor
1). The ZFHX1 proteins are the transcription factors,
which are evolutionally conserved from fly to man,
and harbor two zinc fingers clusters flanking a homeodomain-like
sequence (HD) and one or more binding sites for the
co-repressor CtBP. Both dEF1 and SIP1 bind CACCT consensus
DNA sequence and act as transcriptional repressors.
The recent studies indicate their involvement in the
pathways of TGFb and Hedgehog signaling. To clarify
the roles of these proteins in embryogenesis, knockout
mice of these Zfhx1 family genes have been produced. |
| Fig. 5. ZFHX1 family proteins
and the phenotype of the SIP1 Knockout mouse embryo:
the somites are small and irregular, and the neural
tube is not closed, supporting the view that SIP1 plays
an important role in morphogenesis of these tissues. |
|
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| 6 |
Unorthodox pathways
of cell differentiation. |
| There are unorthodox pathways
of cell differentiation apparently disregarding cell
lineages, which are collectively called "transdifferentiation",
and is often adopted in tissue regeneration. Process
of transdifferantiation and regeneration of lens is
compared with embryonic lens differentiation to reveal
the fundamental mechanisms of cell differentiation. |
| Fig. 6 Multiple pathways to
give rise to lens cells. |
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