ISSN 10623604, Russian Journal of Developmental Biology, 2015, Vol. 46, No. 3, pp. 137–147. © Pleiades Publishing, Inc., 2015.
Original Russian Text © A.S. Kharlamova, V.M. Barabanov, S.V. Saveliev, 2015, published in Ontogenez, 2015, Vol. 46, No. 3, pp. 174–185.
137
INTRODUCTION
The olfactory structure development in humans at
the early stages of prenatal development is thoroughly
addressed in the classical studies (Humphrey, 1940;
Pearson, 1941, 1942; Bossy, 1980; Muller and O’Rahilly,
2004). However, these studies are mainly dedicated to
the development of the peripheral part of the olfactory
system at the early stages of prenatal development
(Pyatkina, 1982; Pearson, 1941, 1942; Bossy 1980;
Muller and O’Rahilly, 2004). Immunohistochemical
(Chuah and Zheng, 1987; Takahashi et al., 1984) and
electronmicroscopic studies (Moran et al., 1982;
Kimura et al., 2009) are also conducted mainly on the
human olfactory epithelium and nerve. Special
aspects of the olfactory bulb (OB) development are
studied on model species, and the obtained results are
either extended to all mammals, including humans
(Valverde et al., 1992; Lin and Ngai, 1999), or studied
within the scope of the general issues of the olfactory
epithelium and nerve development (Chuah and
Zheng, 1992).
Mammalian OB have an organization of six radial
layers: (1) a layer of the incoming olfactory fibers
formed by the olfactory receptor axons, (2) a glomer
ular layer, (3) an external plexiform layer, (4) a mitral cell
layer, (5) an internal plexiform layer, and (6) a granular
layer (Doty, 2012; Huart et al., 2013). In mammals
with larger ventriclecomprising OB, there is also an
additional ventricular cell layer (Nieuwenhuys, 1998).
The ventricles are absent in the OB of an adult human.
The development of human OB is induced by the
olfactory fibers that protrude into the forebrain at the
sixth week of development. At the 7th week, the ana
tomical differentiation of OB begins (Pearson, 1941,
1942). The histological and functional OB differentia
tion at the prenatal stage of human development is
poorly understood, and there are contradictions in the
classical studies (Humphrey, 1940; Muller and
O’Rahilly, 2004).
The first synaptic contacts in the mammalian OB
form axons of the olfactory receptor cells. Their
postsynaptic targets are the dendrites of mitral, tuft,
and periglomerular cells (Grubb et al., 2008). The
areas of these primary contacts form spherical struc
tures—glomeruli. They produce the outermost func
tional layer of the bulb and represent the first region in
Development of Human Olfactory Bulbs in Prenatal Ontogenesis:
An Immunochistochemical Study with Markers of Presynaptic
Terminals (AntiSNAP25, SynapsinI, and Synaptophysin)
A. S. Kharlamova, V. M. Barabanov, and S. V. Saveliev
Laboratory of Nervous System Development, Research Institute of Human Morphology, Russian Academy of Medical Sciences,
ul. Tsyurupy 3, Moscow, 117418 Russia
email: grossu@rambler.ru, grossulyar@gmail.com
Received January 30, 2014; in final form, May 22, 2014
Abstract
—Data on olfactory bulb (OB) development in human fetuses in the stages from the 8th week to birth
is provided. Immunohistochemical markers of presynaptic terminals (antiSNAP25, synapsinI, and syn
aptophysin) were used to evaluate the maturation of the OB. Differentiation of the OB layers begins from the
periphery, which indirectly confirms that growth of the olfactory nerve fibers induces not only the anatomical
differentiation of the OB but also the differentiation of its functional layers. The sites of the developing glom
eruli are revealed using the immunohistochemical procedure prior to the stage in which distinct glomeruli can
be identified using a common histological procedure. The OB conductive system demonstrates immunore
activity with the antibodies to presynaptic proteins at all stages starting with the 10th–11th weeks of fetal
development. Four stages of OB development are described. All functional layers of the OB are mature at the
22nd week stage. Further differentiation of the neuroblasts in the OB, including lamina formation of the
internal granular layer and the glomerular layer development, and the growth of the OB continue after the
20th–22nd week stage until 38th–40th weeks of fetal development. Patterns of the immunoreactivity with anti
bodies to SNAP25, synapsinI, and synaptophysin at the 38th–40th weeks of prenatal development are fully
consistent with those of the adult OB. Complete maturity of the human OB is reached at the 38th–40th week of
prenatal development.
Keywords
: human fetuses, olfactory development, primary olfactory centers, SNAP25, SynapsinI, Synap
tophysin
DOI:
10.1134/S1062360415030054
DEVELOPMENTAL BIOLOGY OF MAMMALS
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