Early Prenatal Development Research Articles

Early dietary sodium restriction disrupts the peripheral anatomical development of the gustatory system.

Dietary sodium restriction has profound effects on the development of peripheral taste function and central taste system anatomy. This study examined whether early dietary sodium restriction also affects innervation of taste buds. The number of geniculate ganglion cells that innervate single fungiform taste buds were quantified for the midregion of the tongue in two groups of rats: those fed either a low-sodium diet and those fed a sodium replete diet (control rats) from early prenatal development through adulthood. The same mean number of ganglion cells in developmentally sodium-restricted and control adult rats innervated taste buds on the midregion of the tongue. However, the characteristic relationship of the larger the taste bud, the more neurons that innervate it did not develop in sodium-restricted rats. The failure to form such a relationship in experimental rats was likely due to a substantially smaller mean taste bud volume than controls and probably not to changes in innervation. Further experiments demonstrated that the altered association between number of innervating neurons and taste bud size in restricted rats was reversible. Feeding developmentally sodium-restricted rats a sodium replete diet at adulthood resulted in an increase in taste bud size. Accordingly, the high correlation between taste bud volume and innervation was established in sodium-replete rats. Findings from the current study reveal that early dietary manipulations influence neuron-target interactions; however, the effects of dietary sodium restriction on peripheral gustatory anatomy can be completely restored, even in adult animals.

Localization of glutamate in the human retina during early prenatal development

In this study we have localized glutamate (GLU) in fetal (14–25 weeks gestation, Wg) human retinas by immunohistochemistry. At 14 Wg, GLU-immunoreactivity (IR) was localized only in the central part of retina, showing a prominently labelled nerve fiber layero A few ganglion cells and displaced amacrine cells were very weakly labelled. At 17 Wg, GLU was localized conspicuously in many ganglion cells, displaced amacrine cells, some amacrine cells and the prospective photoreceptor cell bodies in the neuroepithelial layero With progressive development at 20 and 25 Wg, the IR for GLU was found additionally in the Muller cell endfeet, some bipolar cells as well as in the horizontal cells that were aligned in a row along the outer border of the inner nuclear layer of the central retinao The photoreceptor cell bodies in the outer nuclear layer were also prominently immunopositive for GLU. The developmental distribution of GLU in the human retina tends to indicate that it plays an important role in the differentiation and maturation of retinal neurons.

Development of the Pathway From the Reticular and Perireticular Nuclei to the Thalamus in Ferrets: A Dil Study

This study examines the connections of the thalamic reticular and perireticular cell groups in developing ferrets. Small crystals of Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) were implanted into either the dorsal thalamus or the cerebral cortex of aldehyde-fixed prenatal and postnatal ferret brains. A small implant of Dil into the presumptive lateral geniculate nucleus during early prenatal development [between embryonic day 23 (E23) and E25] reveals many retrogradely labelled cells in the reticular nucleus. At E40, just before birth, the number of cells retrogradely labelled in the reticular nucleus has become reduced compared to earlier prenatal implants, whether from small or large implants of Dil into the lateral geniculate nucleus. By postnatal day 7, an adult-like pattern of retrograde labelling is seen in the reticular nucleus; at this age, a small implant of Dil limited to the lateral geniculate nucleus retrogradely labels a discrete group of cells located in the caudal regions of the reticular nucleus. In the internal capsule, adjacent to the reticular nucleus, there are two distinct groups of neurons. One group, called the large-celled perireticular zone (LPR), enters the internal capsule very early in development (from E25; Mitrofanis, J., Eur. J. Neurosci., 6, 253-263, 1994) and is not labelled from the lateral geniculate nucleus at any developmental stage. Small implants of Dil into presumptive visual and somatosensory cortices shows that the LPR lies in a distinct region of the primordial internal capsule. Corticothalamic and thalamocortical axons turn sharply in the region of the LPR, whilst corticospinal and corticobulbar axons pass straight through the LPR on towards their more caudal targets. Later, after both sets of axons have reached their targets, the LPR is not seen in the internal capsule. The other group of cells in the internal capsule, called the small-celled perireticular zone (SPR), forms a distinct band of cells lying midway between the reticular nucleus and the globus pallidus. These cells enter the internal capsule much later in development, at about E40. Unlike the cells in the LPR, cells in the SPR are retrogradely labelled after an implant of Dil into the lateral geniculate nucleus, and there are many which remain in the adult (Clemence, A. E. and Mitrofanis, J., J. Comp. Neurol., 322, 167-181, 1992).

Human Fluctuating Asymmetry and Sexual Behavior

This report presents evidence that sexual selection may favor developmental stability (i e, the absence of fluctuating asymmetry) in humans Subtle, heritable asymmetries in seven nonfacial human body traits correlated negatively with number of self-reported, lifetime sex partners and correlated positively with self-reported age at first copulation in a college student sample These relationships remained statistically significant when age, marital status, body height, ethnicity, physical anomalies associated with early prenatal development, and physical attractiveness were statistically controlled The strength of the relationships did not differ significantly as a function of sex It is unlikely that the relationships are generated by false self-reporting of sexual experience

Development of the thalamic reticular nucleus in ferrets with special reference to the perigeniculate and perireticular cell groups.

This study describes the development of the ferret thalamic reticular nucleus from Nissl-stained and from parvalbumin-immunostained sections. From early stages [embryonic day (E) 23-E25], there is a large group of ventral thalamic cells which lies between the dorsal thalamus and the primordial internal capsule. This group of cells, the primordial reticular nucleus, gives rise to the main body of the reticular nucleus, the perigeniculate nucleus and the perireticular nucleus. In the reticular nucleus, there are two waves of parvalbumin expression during development. The first wave begins prenatally in small cells which are seen rarely after birth. Their fate is not clear: they may have lost immunoreactivity, migrated elsewhere, or died. At the end of the first wave, a second wave begins in a distinct group of larger ovoid reticular cells, which appear to remain into adulthood. At about birth, the dorsocaudal pole of the reticular nucleus first forms the perigeniculate nucleus. During this developmental stage, cells which make up the reticular and perigeniculate nuclei are the only parvalbumin-immunostained structures in the thalamus. Thus, rather than develop from the dorsal thalamus, the perigeniculate nucleus seems to have its origins in the ventral thalamus together with the reticular nucleus. During development, the reticular nucleus is associated closely with a large mass of cells located in the internal capsule, called the perireticular nucleus. Later, the perireticular nucleus is dramatically reduced in size: that is, there is a large reduction in the number of perireticular cells seen per section and in the extent of the nucleus across the internal capsule. There are two cytoarchitectonically distinct groups of perireticular cells. One group of cells, called the large-celled perireticular zone (LPR), enters the internal capsule from early prenatal development (E25). Many of these cells reach the globus pallidus and extend as far as the cortical subplate zone. The LPR together with the subplate form an extensive neuronal network in the white matter during early development, which disappears later in development (about postnatal day 20). The second group of perireticular cells is made up of smaller cells and is called the small-celled perireticular zone (SPR). These small cells enter the internal capsule from the reticular nucleus just prior to birth. Many of the cells in the SPR remain in the adult.

Prenatal development of the retinohypothalamic pathway and the suprachiasmatic nucleus in the sheep

Circadian rhythms are present during fetal life in several mammalian species. To characterize the ontogeny of the neural mechanisms that account for circadian rhythmicity in a precocious species, we studied the prenatal development of the retinohypothalamic pathway in lambs (gestation period of 147 days), using horseradish peroxidase and wheat germ agglutinin as anterograde tracers. The suprachiasmatic nucleus was present as early as embryonic day 52 (E52). After E58, the suprachiasmatic nucleus reached its full number of neurons, estimated by the disector method in about 160,000 cells per nucleus at E62. The retinohypothalamic axons invaded the suprachiasmatic nucleus from E58, while neuroblasts were still migrating to the nucleus. At E62, there was a strong retinal projection that evolved until E121, when the retinal afferents established their definitive pattern of distribution in the ventral and central regions of the suprachiasmatic nucleus, and adjacent hypothalamic structures. The development of the retinohypothalamic pathway was delayed by about a week relative to the innervation of other subcortical visual centers. The present findings demonstrated an early prenatal development of the visual pathways in lambs, including the retinohypothalamic pathway, suggesting that the mechanisms for the visual entrainment of circadian rhythms in lambs may be functioning several weeks before birth.

Immunohistochemical localization of nerve growth factor receptor in the cochlea and in the brainstem of the perinatal rat

Nerve growth factor receptor (NGF-R) localization was studied immunohistochemically in the cochlea and in the brainstem of the perinatal rat, using a specific monoclonal antibody directed against the rat NGF-R. In the cochlea, NGF-R immunoreactivity is positive during the whole perinatal period studied, and is located at the hair cell level, in fibers that reach the organ of Corti, in the intraganglionic spiral bundle and in some small bundles of fibers in the auditory nerve. In the brainstem, NGF-R is detected in auditory structures such as the ventral cochlear nucleus, the superior olivary complex, the nuclei of the trapezoid body and the trapezoid body. Many auditory structures labelled by the NGF-R antibody are implicated in the efferent cochlear innervation. These results suggest that NGF could be implicated in interactions between auditory receptors and efferent innervation of the developing cochlea. This coincides with findings on the immunohistochemical localization of NGF-like protein in the organ of Corti of the developing rat. Moreover, these observations could be related to an early prenatal development of auditory efferent innervation.

Development of Receptors for Insulin and Insulin-Like Growth Factor-I in Head and Brain of Chick Embryos: Autoradiographic Localization*

In whole brain of chick embryos insulin receptors are highest at the end of embryonic development, while insulin-like growth factor-I (IGF-I) receptors dominate in the early stages. These studies provided evidence for developmental regulation of both types of receptors, but they did not provide information on possible differences between brain regions at each developmental stage or within one region at different embryonic ages. We have now localized the specific binding of [125I]insulin and [125I]IGF-I in sections of head and brain using autoradiography and computer-assisted densitometric analysis. Embryos have been studied from the latter part of organogenesis (days 6 and 12) through late development (day 18, i.e. 3 days before hatching), and the binding patterns have been compared with those in the adult brain. At all ages the binding of both ligands was to discrete anatomical regions. Interestingly, while in late embryos and adult brain the patterns of [125I]insulin and [125I] IGF-I binding were quite distinct, in young embryos both ligands showed very similar localization of binding. In young embryos the retina and lateral wall of the growing encephalic vesicles had the highest binding of both [125I]insulin and [125I]IGF-I. In older embryos, as in the adult brain, insulin binding was high in the paleostriatum augmentatum and molecular layer of the cerebellum, while IGF-I binding was prominent in the hippocampus and neostriatum. The mapping of receptors in a vertebrate embryo model from early prenatal development until adulthood predicts great overlap in any possible function of insulin and IGF-I in brain development, while it anticipates differential localized actions of the peptides in the mature brain.

The localization of laminin mRNA and protein in the postimplantation embryo and placenta of the mouse: an in situ hybridization and immunocytochemical study.

In situ hybridization (ISH) and immunocytochemistry were used to localize sites of synthesis and deposition of the basement membrane glycoprotein laminin during development in the postimplantation mouse embryo and extraembryonic membranes. In addition, similar studies were performed on postnatal viscera during the first 20 days after birth. Up to 10 days post coitum, embryonic laminin synthesis was confined to parietal endoderm. In maternal tissue, intense laminin mRNA expression was detected in decidual cells in the mesometrial and antimesometrial endometrium at 5-7 days. At 10 days, uniform expression was still seen within the mesometrial endometrium, with higher levels around migrating trophoblast, but in the antimesometrial aspect expression was restricted to the basal zone. High levels of mRNA expression persisted in parietal endoderm throughout gestation but much lower levels were detected in visceral yolk sac. In the mature placenta, laminin mRNA expression was also found associated with fetal vessels in the labyrinth and giant cells at the fetal/maternal boundary. In the embryo, the external limiting membrane of the cerebral vesicles and spinal cord stained for laminin protein and detectable mRNA was found in the pia mater. Growing peripheral nerves and dorsal and ventral root fibres expressed laminin mRNA and stained for laminin protein. Laminin mRNA expression was found in ureteric buds and nephrogenic vesicles (but not in metanephric blastema) during early prenatal kidney development, and in glomeruli, Bowman's capsule, loops of Henle and collecting duct cells at later stages of development, and after birth. All these structures possessed laminin-rich basement membrane (BM). Laminin mRNA expression fell to below detectable levels in the kidney around weaning. In the gut, laminin expression and protein staining was confined to the muscularis externa and the lamina propria during embryogenesis. After birth, the muscularis externa, muscularis mucosa and lamina propria cells corresponding to fibroblasts had detectable laminin mRNA, but in adult gut no laminin mRNA could be demonstrated in any cell type. In liver, low levels of laminin mRNA were seen in the capsule and in periportal connective tissue. After birth, laminin mRNA was associated with intrahepatic bile channels; no laminin mRNA was detected in the parenchyma and protein deposition was restricted to blood sinus BM. In the adult liver, no laminin mRNA was detected in any cell type. The developing heart showed uniform expression of laminin mRNA from 12 days to before birth. Postnatally, labelling was restricted to connective tissue cells.

Human brain synapses during early prenatal development

The principles governing development of the human brain, especially in the early period of its antenatal ontogeny, haverecently assumed particular importance. The undoubted key factor in individual formation of the human brain is early synaptogenesis, which leads to the appearance of the first neuronal nets, responsible for the formation of the specific functions of this developing organ. However, the process of formation of synaptic connections in the presumptive human brain and, in particular, in its cerebral cortex, has received very little study. We could find only one reference [i] in which true synaptic interneuronal junctions were described in the cerebral cortex of human fetuses, the earliest of which was aged 9 weeks.

Evidence for the early prenatal development of cortical cholinergic afferents from the nucleus of Meynert in the human foetus

A combined histochemical and biochemical approach has shown that the cholinergic system in the nucleus of Meynert region of the substantia innominata is well defined both histochemically and neurochemically within the first 3 months of gestation in the human foetus. Thus, at between 12 and 22 weeks of development the most intense acetylcholinesterase (AChE) histochemical reactivity was observed in the neuropil, cell bodies and processes in the nucleus of Meynert. AChE-stained fibres were observed which coursed from the nucleus of Meynert towards the cortical mantle and within the mantle AChE-stained fibres were also present. Micropunch samples from within the nucleus of Meynert contained higher levels of choline acetyltransferase (ChAT) activity than any other area examined including the striatum, while in the cortical mantle the level of ChAT activity was comparable to that found in the adult cerebral cortex. These observations suggest that the cholinergic innervation from the nucleus of Meynert - considered to be the major source of cholinergic afferents in the adult cerebral cortex - may play a key role in the early development of the human neocortex.

Early prenatal development of the human precommissural septum.

The development of the septum was studied in human embryos and fetuses ranging from 8 to 24.5 weeks of menstrual age (22.2 to 216 mm crown-rump length). Neuroblasts migrating from the ventricular layer of the ventromedial hemispheric wall form a narrow intermediate layer that constitutes the primordial septum (8 weeks). Only a primordial nucleus of the diagonal band is identifiable within the gradually enlarging primordial septum at early stages. By 10 weeks the primordial septum is subdivided into medial and lateral zones. At 11.5 weeks well-defined medial nuclei and the nucleus of the diagonal band are evident within the medial zone. Differentiation within the lateral zone occurs by 12.5 weeks with the appearance of nucleus lateralis pars interna. Nucleus dorsalis is developing in the lateral zone by 14.5 weeks and, by 15.5 weeks, well-defined nuclei are present throughout the lateral zone. Further neuronal maturation and conformational changes result in the nearly adult appearance of the septum in older fetuses. Although a definite mediolateral differentiation-gradient occurs, individual nuclei appear to differentiate along their own longitudinal gradient. Evidence presented suggests that the earliest fibers within the primordial septum are related to the tuberculum olfactorium and the medial forebrain bundle, that septohippocampal fibers appear at 10 weeks, hippocamposeptal fibers by 11.5 weeks, and that, later, stria terminalis fibers develop. The suggested developmental relationships of the septum with the hypothalamus (and brainstem), tuberculum, hippocampus, and amygdala emphasizes its role as an internode in the limbic system.

Growth and development of human adipose tissue during early gestation.

805 normal-for-age human embryos and fetuses were used to study early prenatal fat development. The investigation included observations on stages of fat morphogenesis at the light microscopic level and computerized image analyses of fat lobule size and number. The buccal fat pad was selected as a model system for the analyses. Fat tissue differentiates between the 14th and the 16th weeks: there are five morphogenic phases in adipose tissue formation, strongly associated with the formation of blood vessels. Fat lobules are the earliest structures to be identified before typical vacuolated fat cells appear. Concerning fat lobule size and number, we show that after the 23rd week the total number of fat lobules remains approximately constant, while from the 23rd to 29th week the growth of adipose tissue is determined mainly by an increase in size of the lobules. These results suggest that the 14th through the 23rd week is a sensitive period in fat lobule development, and that disturbances of normal adipogenesis during this period may play a role in the etiology of obesity in later life.

Early prenatal development of substance P and enkephalin-containing neurons in the rat.

The peroxidase-antiperoxidase (PAP) technique is used to determine the time of first detection and distribution of neuronal perikarya and processes showing substance P (SP)- and enkephalin (EN)-like immunoreactivity (LI) in the central and peripheral nervous system of the fetal rat. SPLI is first detected in central perikarya at E15. By E18, SPLI is less intensely localized in certain nuclei and shows heavier accumulations of immunoreactivity in central processes and in peripheral sensory neurons. ENLI is also widely distributed in perikarya and processes of the central nervous system at E18, but is not detected at E15. The distribution of SPLI and ENLI at E18 is comparable to that previously described in the adult brain with the following exceptions: (1) labeled perikarya and processes are not detected in the rostral forebrain; (2) axonal pathways are intensely labeled whereas most terminal fields are devoid of immunoreactivity.

Prenatal and postnatal development of the cervical portion of the spine in the short‐finned pilot whale Globicephala macrorhyncha

Fusion of the cervical spine in Globicephala macrorhyncha is a prenatal rather than a postnatal phenomenon which encompasses all cervical vertebra. This results in a relatively short, nonarticulated, composite cervical spine in this particular species. Cervicothoracic spine segments removed from fetuses demonstrated complete fusion of all cervical vertebra commencing during early prenatal development. C1 and C2 initially developed as a composite central cartilaginous unit, although laterally there was some separation through rudimentary interzone formation. However, C3 through C7 formed individual cartilaginous centra which were divided from each other by thin, well-demarcated concomitantly evident dividing the thoracic, lumbar, and caudal vertebra, although this was a very rudimentary intervertebral region). The first primary ossification center appeared in C2. Subsequently, primary ossification occurred in C7, and finally in C2 through C6, with ossification centers then progressively coalesced in the midline, from C2 to C7, in a craniocaudal sequence. This entire chondroosseous fusion process was completed during early gestation (probably less than 2 to 3 months of prenatal development), so that a composite "single" cervical vertebra developed that characterizes this species at birth and throughout postnatal development. Postnatally, ossification spreads laterally within each centrum, and also progressively removes the vestiges of the intervertebral material. The cranial end of C7 and the remainder of the cervical vertebra do not form secondary centers. An extensive fibrocartilaginous/hyaline cartilage bridge remains between C1 and C2, even after closure of the vertebral physes. Undoubtedly, this allows continued growth in C1 and C2, which become the dominant portion of the cervical unitary vertebra. Eventually, even this synchondrosis will disappear to form a completely osseous cervical mass.

Prenatal selection and dermatoglyphic patterns.

AbstractAlthough human dermatoglyphics have been extensively studied, little is known of the prenatal origins of dermatoglyphic patterns. Digital patterns, i.e., loops, whorls, and arches, were obtained from 81 human abortuses, ranging in age from 11 to 25 weeks post‐fertilization. Patterns were discernible with the earliest indications of epidermal ridge development. Findings indicate that pattern frequencies during early prenatal development differ from those of later fetal and postnatal periods. Furthermore, a high frequency of arches is seen associated with spontaneous abortion, suggesting evidence for prenatal selection in human abortuses.

Development of interneuronal synapses between anterior horn neuroblasts of the human spinal cord in early prenatal development (seventh to ninth weeks of gestation)

Synaptogenesis in presumptive anterior horn cells of the spinal cord (C4-T3) was studied by electron microscopy in early human prenatal development. The morphological stages of synaptogenesis were traced and the minimum structural organization of the synapse corresponding to the onset of its functional activity was identified. The possible mechanisms of synaptogenesis are postulated.

Prominent lateral palatine ridges: Developmental and clinical relevance

Unusually prominent lateral palatine ridges have been found to be a nonspecific feature of a variety of disorders in which there is either neuromotor dysfunction or a malformation which prevents tongue thrust into the palatal vault. Observations of the lateral palatine ridges in 3 fetal specimens and in 260 normal individuals over a wide range of ages revealed that these structures are normally more prominent during prenatal life and infancy. With increasing age these ridges normally become progressively flattened and usually disappear by age 5 years. The observation of unusual prominence of these ridges in infants with neuromuscular dysfunction as well as in those with malformations which limit tongue thrust into the palatal vault suggests that a long-standing deficit of tongue thrust is the common pathogenetic mechanism. Prominent lateral palatine ridges may be misinterpreted as a true "narrow, high-arched palate", which is a much less common anomaly. This distinction is important clinically, since prominent lateral palatine ridges most commonly imply a long-term deficit of neuromuscular function and thus may be an important diagnostic clue to alterations dating back to early prenatal development.

Induced chromosomal aberrations in pronuclei, 2-cell stages and morulae of mice

C 3H female mice, 10–12 weeks old, were treated in the pre-ovulatory phase of oogenesis or in the first mitotic interphase after fertilization with amethopterin (M) at 200 mg/kg body weight. The females were mated with untreated males of the same age group and strain and were checked hourly for vaginal plugs. At different times after fertilization the oviducts of the females of experiment and control were flushed out and the cleavage stages obtained were examined cytologically. Chromosome analysis was performed in the pronucleus stage, in the 2-cell stage and in morulae. Separate analyses of maternal and paternal chromosomes of the pronucleus stage can show whether the spontaneous or induced aberrations are derived from oogenesis or spermatogenesis. After treatment the frequency of numerical and structural aberrations increased compared with the matched control. During the early prenatal development at least 2 steps seem to be important for the elimination of chromosomal aberrations: 1, from the unfertilized mII oocyte to the pronucleus stage; and 2, from early morulae to the registration of dominant lethal mutations.

Early prenatal development of cortical surface responses to visual stimuli in sheep

Cortical surface responses to electrical stimulation of the optic nerve were recorded in sheep fetuses between 55 and 124 days of gestation (term 145 days). The cortical response obtained in the youngest fetuses was a long-latency surface-positive wave, followed by a small negativity. Later during development the negativity increased in amplitude and dominated the response. This early developmental pattern of the visual response was similar to that of the somesthetic response. On basis of findings on the maturation of structure and function in the somesthetic cortex the genesis of the visual response is discussed. The hypothesis is put forward that, at its earliest appearance, the positive wave of the visual response is predominantly reflecting synchronous depolarization of developing corticopetal nerve terminals and later arises from summation of excitatory postsynaptic potentials of deep-seated cortical neurons. The surface negativity of the response is considered to reflect excitatory postsynaptic activation of neural elements in the superficial neocortex. At about 98 days of fetal age a short-latency component appeared in the response. It is suggested that this component is mediated through the specific optic pathways, whereas the earlier-appearing long-latency response is suggested to be mediated via the unspecific visual projection. During the succeeding development the two components apparently coalesced to build up a positive-negative response containing all elements of the adult form.