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Abstract:
Islet-1, Islet-2 and Islet-3 in zebrafish
(Danio rerio)
constitute a family (the Islet-1 family) of LIM/homeodomain-type
transcription factors which have been implicated in cellular and
regional specification of the developing nervous system. Islet-3 is
expressed specifically in the eyes and the presumptive tectum.
Overexpression of the protein (LIM
Isl-3
) consisting only of the Islet-3 LIM domains in embryos
specifically prevented formation of the optic vesicles, caused
abnormal termination of the expression of
wnt1, engrailed2
and
pax2
in the mesencephalic and metencephalic region between 14 and 20
hours post fertilization, and ultimately resulted in the specific
deletion of the cerebellar primordium at the junction between the
mesencephalon and the metencephalon. Such defects were rescued by
simultaneous overexpression of Islet-3, suggesting that
overexpression of the LIM domains of Islet-3 affected the eye and
cerebellar development by antagonizing the functions of the
endogenous Islet-3. Overexpression of the LIM domains of Islet-2
cell-autonomously disrupted the regular arrangement, the axonal
pathfinding and the neurotransmitter selection by the
Islet-2-
positive primary motor neurons, and the peripheral axon outgrowth
by the
Islet-2
-positive primary sensory neurons. In contrast, overexpression of
the LIM domains of Islet-1 only induced ectopic expression of
Islet-2
mRNA in the ventral neurons. Defects in the motor and sensory
neurons caused by overexpression of the LIM domains of Islet-2 were
rescued by coexpression of the full-length Islet-2, but not by
Islet-1 nor Islet-3. Our data support that each subtype of the
Islet-1-family plays the highly specialized roles in neural
differentiation. In this symposium, I will discuss on the
functional analyses of the Islet-1 family members and also talk
about the research that we are currently undertaking to identify
the downstream target genes and the regulatory elements of the
Islet-1 family genes.
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