Page 113 - 80_02

The
role
of
the
catecholaminergic…

It
appears
that
tissue
GH
may
act
in
paracrine
or
autocrine
fashion
to

control
proliferation
and
differentiation,
although
a
full
characterization
is
not

avalilable.
In
studies
carried
out
over
the
last
three
decades,
we
showed
that
the

expression
of
proinsulin
(molecular
precursor
form
of
insulin)
antecedes
the

development
of
the
pancreas
(2,
3)
and
it
has
a
cell
survival
function
in
the

developing
nervous
system
(4,
5).
Proinsulin
expression
is
tightly
regulated
as
well

in
the
heart
tube,
and
malformations
are
induced
when
proinsulin
is

disproportionally
high
at
early
stages
(6).

Catecholamines
are
well
known
essential
hormones/neurotransmitters

during
postnatal
life,
when
they
have
cardiovascular,
neuromuscular
and

behavioral
effects,
but
their
function
in
specific
organs
during
vertebrate

development
is
poorly
characterized
(7).
The
catecholamine
synthetic
pathway

(Figure
1)
is
initiated
by
the
action
of
Tyrosine
Hydroxylase
(TH)
which
catalyses

the
conversion
of
the
amino
acid
L-­-tyrosine
to
L-­-3,4-­-dihydroxyphenylalanine
(L-­-
DOPA);
in
subsequent
reactions,
dopamine,
noradrenaline
and
adrenaline
may
be

produced.
While
we
were
studying
proinsulin
transcripts
regulation
in

development
we
found,
to
our
surprise,
non-­-canonical
th-­-insulin
chimeric
mRNA

transcripts
(8);
this
finding
motivated
further
work
on
the
presence
and
function

of
TH
in
early
embryogenesis.

2.
TYROXINE
HYDROXYLASE,
A
GENE
WITH
COMPLEX
TRANSCRIPTIONAL

REGULATION

As
commented
above,
genes/proteins
have
mechanisms
of
regulation
and

functions
at
certain
developmental
stages
of
vertebrates
distinct
from
their

canonical
roles
later
in
life.
In
this
context,
while
the
th
and
ins
genes
are
located
in

tandem
in
the
same
orientation
(and
they
are
generally
transcribed

independently),
two
chimeric
transcripts
containing
exons
from
both
of
these

genes
can
also
be
produced
in
a
regulated
manner
during
the
first
few
days
of

development
in
the
chick
and
quail
embryos
(Figure
2).

It
is
estimated
that
between
2
and
5%
of
tandem
human
genes
may
be

transcribed
into
chimeric
mRNAs
(9-­-11),
although
the
function
of
these
unusual

transcripts
is
in
general
unknown.

349