The roleof the catecholaminergic…
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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
developingnervous system(4, 5). Proinsulinexpression is tightly regulatedaswell
in the heart tube, and malformations are induced when proinsulin is
disproportionallyhighat earlystages (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 TyrosineHydroxylase (TH) which catalyses
the conversion of the amino acid L-‐tyrosine to L-‐3,4-‐dihydroxyphenylalanine (L-‐
DOPA); in subsequent reactions, dopamine, noradrenaline and adrenalinemay 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 findingmotivated further work on the presence and function
ofTHinearlyembryogenesis.
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 thand 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 inthechickandquail embryos (Figure2).
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 ingeneral unknown.
