ISSN 1062-3604, Russian Journal of Developmental Biology, 2007, Vol. 38, No. 4, pp. 213–220. © Pleiades Publishing, Inc., 2007.
Original Russian Text © G.A. Buznikov, 2007, published in Ontogenez, 2007, Vol. 38, No. 4, pp. 262–270.
Classical neurotransmitters, such as acetylcholine,
serotonin, and catecholamines, function not only as
synaptic transmitters, but also regulators of early (pre-
neural) embryogenesis, what became known about 45
years ago (Koshtoyants et al., 1961; Buznikov, 1963;
Buznikov et al., 1964). Already within a few years, the
ﬁrst review of the problem of preneural transmitters
was published, concerning mostly their ﬁnding in dif-
ferent animals, both vertebrates and invertebrates
(Buznikov, 1967). These data were conﬁrmed and sup-
plemented by the 1980s (Gustafson and Toneby, 1970;
Toneby, 1977; Renaud et al., 1983; Buznikov, 1984).
The ﬁrst data were obtained about functional coupling
of preneural transmitters and intracellular regulatory
cascades (Renaud et al., 1983; Shmukler et al., 1984;
Rostomyan et al., 1985). These results were discussed
in the next series of reviews (Buznikov, 1987, 1990;
Pendleton et al., 1998; Azmitia, 2001) and a scheme
was proposed, which described the age-related dynam-
ics of embryogenetic functions of preneural and non-
neural transmitters (Buznikov et al., 1996). We con-
tinue our experiments until the present time and the
number of researchers in this ﬁeld increased. The infor-
mation about the corresponding regulatory systems was
checked using the modern methods; the ﬁrst molecular-
biological and immunocytochemical data were
obtained about the presence and localization of trans-
mitters, their receptors, and transmitter proteins in cells
of the developing embryos, as well as about a possible
role of preneural transmitters in regulation of the
genome activity. The early (preneural) embryos of var-
ious animals, especially sea urchins, were used more
and more often as biosensor for ﬁnding and studying
pharmacologically active substances, testing of terato-
genic activity of chemical pollutants, and searching for
the corresponding antidotes. This progress in the area
of preneural transmitters makes is necessary at least a
brief review of the new results.
ARE THERE PRENEURAL TRANSMITTER
If the existence of functionally active preneural neu-
rotransmitters is for some specialists in the area of neu-
robiology and developmental biology obvious and does
need special investigation, it is for some others abso-
lutely impossible and, for this reason, also does not
deserve investigation. Naturally, both are wrong, but
such diametrically opposite viewpoints call for the
necessity of checking the existence of preneural trans-
mitter systems using the modern methods. This work
was and is carried out by many researchers and, as a
result, the range of preneural transmitters was widened
and new, previously unknown, although postulated,
Preneural Transmitters as Regulators of Embryogenesis.
Current State of Problem
G. A. Buznikov
Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, ul. Vavilova 26, Moscow, 199334 Russia
University of North Caroline, Chapel Hill, NC 27599, USA
Received April 19, 2006; in ﬁnal form, July 4, 2006
I dedicate this review to the surgeon Professor Philip Walter,
Duke University Hospital, thanks to whom I continue
to work and crossed the 75-year threshold.
—Our knowledge about the preneural neurotransmitter systems and their functions were based on the
old pharmacological and biochemical data that have recently been conﬁrmed and substantially supplemented.
Speciﬁc components of the preneural serotoninergic and endocannabinoid systems were identiﬁed in develop-
ing echinoderm embryos using immunocytochemistry, Western immunoelectroblotting, and HPLC-mass spec-
troscopy. These data were corroborated by the results of pharmacological experiments: it was found that some
ligands of serotonin receptors, as well as the agonist of cannabinoid receptors anandamide induced the appear-
ance of abnormal embryonic phenotypes, whose expression depended on the ligand-teratogen concentration.
Their appearance was prevented, correspondingly, by serotonin and its lipophilic (or hydrophilic) analogs and
antagonists of cannabinoid (CB
: serotonin, serotonin receptors, cannabinoid receptors, sea urchin embryos.