
EARCH THEMES IN OUR LABORATORY
Molecular mechanisms of cortical development: How does the neocortex develop? To address
this question (and look for the ways to repair
the damaged brain), we have been studying
the development of the brain, focusing on
the phenomenon happening in the ventricular
zone (germinal zone, neuroepithelium) of
the neocortex. Most cortical neurons are
born in the ventricular zone, differentiate,
migrate out of the ventricular zone, then
form the neocortex. We have cloned several
novel molecules expressed in the ventricular
zone and tried to elucidate functions of
these molecules in order to reveal the mechanisms
serving for differentiation of neurons, layer
fate decisions and regulation of the migration
start.
Recently we cloned novel molecules (we call
'FILIP') of which mRNAs are located in the
ventricular zone. FILIP regulates cortical
neurons out of the ventricular zone by inducing
the degradation of actin-binding protein,
Filamin A (Nagano, T. et al., Nature Cell
Biology). When to start migration is essential
to form 6 layers, typical feature of neocortex,
and FILIP is a key molecule controlling this
process. Details will be introduced in highlight
section of 'Nature Reviews, Molecular Cell Biology,
July issue, 2002'. We are now studying on the regulatory mechanisms
of FILIP and Filamin A.
Molecular mechanisms of maturation of neuronal
circuits: Pyramidal tracts are good examples for
studying the maturation of neuronal circuits.
Adult pattern of pyramidal tracts projections
is established through collateral branching
and pruning from immature form of projections.
We would like to address for the molecular
bases of this maturation process.
Functions of TBPIP: TBPIP is a novel molecule that we cloned
several years ago. TBPIP could enhance the
function of TBP-1 of 26S proteasome and the
activities of nuclear receptors. Also, its
robust expression in the testis along with
other data suggests that TBPIP is involved
in meiosis. We are pursuing the precise molecular
mechanisms underlying these apparent distinct
functions of TBPIP by several approaches