Neocortical development in IL-9 transgenic mouse brain

S287

NEOCORTICAL

641

DEVELOPMENT

, KEIICHI UYEMURA’,

KAYOKO ISHIIl,2

IN IL-9 TRANSGENIC

JEAN-CHRISTOPHE

RENAULD2

Shinjuku-ku,

Dept. of Physiology, Keio Univ. School of Medicine’, School of Medicine. Brussels B- 1200, Belgium

MOUSE BRAIN

Japan. ‘Catholic

Tokyo 1608582,

Univ. of Louvain

We studied a possibility that interleukin 9 (IL-9), a growth factor for immune and cancer cells, might modulate early stage of corticogenesis in embryonic brain. In newborn homozygotes from transgenic mice which express high level of IL-9, the wet weight of forebrain was greater than in control mice, in spite of no significant change in other brain areas and whole body. By mitotic labeling with bromodeoxyuridine, the number of proliferating cells was greater by 63% and mitotic zone was wider in the transgenic neocortex on the 14th gestation day (E14). An advanced neuronal maturation was indicated by matured cytoarchitecture in the primordial plexiform layer and the intermediated zone and by wider distribution of MAP2 immunoreactivity in the medial neocortex. In transgenic cortex, IL9 mRNA and IL-9 protein were detected abundantly already at El 1 by RTPCR and bioassay. Messenger RNA for IL-9 receptor was detected in brain from both transgenic and wild embryos. On postnatal day 5th, incidense of apoptosis in the gray matter of transgenic neocortex was rather below of control level indicating a possibility that excess neural cells survive in the transgenic brains. These results suggest that endogenou\ IL9 and its receptor may influence the development of embryonic neocortex and hense that of postnatal brain.

ENHANCED

642

SURVIVAL

BY MACROPHAGE

YASUKO

TOMOZAWA,

SHINJI

Dept. of Dynamic Pathology, Kamigyo-ku,

AND DIFFERENTIATION

COLONY-STIMULATING FUSHIKI

Research

and

OF CULTURED FACTOR

YOHKO

Institute for Neurological

CENTRAL

NEURONS

(M-CSF)

TSUTSUMI

Diseases

and Geriatrics,

Kyoto Pref. Univ. of Medicine,

Kyoto 602-0841

In normaI rat CNS, astrocytes produce M-CSF from the embryonic

through adulthood.

the site of brain injuries

In this study,

differentiation

and some neurodegenerative

of cultured

immunofluorescence

mesencephahc

neurons

diseases. from

embryonic

The activities of M-CSF are increased at

the effects of M-CSF

14- to 19-day-old

stainings of MAP2 antigen for aII neurons and tyrosine hydroxylase

rats

were

on the survival examined

antigen for dopaminergic

neurons.

When M-CSF was added to the culture medium at around 1 ng /ml, (1) M-CSF enhanced neuronal survival up to 3.6-fold remarkably

increased

populations

of central neurons,

the number of neurites per ceII and the length of neurites, (3) these stimulatory

neurons when prepared from embryonic

effects,

Analyses

neuroepithelium

dopaminergic

neurons,

in the developing

and injured CNS,

in a stage-specific

of the rat

H. Yagi.7, M. Sate:

‘Dept. Structural Cell Biology, NAIST , 2Dept

ofAnatomy

and Neuroscience,

Osaka Univ

Med. Sch., 32nd. Dept

Faculty of Med ) Fukui Med. Univ

of Anatomy,

We have cloned a novel gene (neurepin) embryogenesis

that is expressed

in the rat. Immunohistochemical

locahzed in the neuroepithelium. We have further investigated

especially

restrictly

taken from the embryonic

during the middle stage of immunoreactivity

is

m the mitotic neural stem cells that are located adjacent to the ventricles

the role of Neurepin

by increasing Neurepin

with the followmg two cells 1) immortalized

provided from Dr.Nakafuku)

in the neuroepithelium

analyses have shown that Neurepin-like

vector) and/or inhibiting neurepin mRNA expression

oligonucleotides)

experiments

the survival of aLl

in vitro, were more obvious on long innervating

of a novel gene. neurepin. which is expressed

manner in the embryonic

D. Konno 1.:. T Yonedaz, T.Naganoj.

expression

enhanced

and

19-day-old rats. These in vitro results suggest that M-CSF may play an important role

of neuronal survival and growth, especially dopatninergic

643

(2) M-CSF

and

by double

neuroepithelial

in which we have confirmed the expression

rat Possible in\.olvement

expression

(by applying

of Neurepin

(by transfecting

the neurepin-

neurepin mRNA antisense cell line, MNS cells (generously

of neurepin mRNA

2) neuroepithelial

on the neural cell division is revealed by these

cells