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J M Lauder

Publications and source records attributed to J M Lauder.

At least 19 recordsLinked to original sources

Serotonin promotes region-specific glial influences on cultured serotonin and dopamine neurons.

To test the hypothesis that glia mediate interactions between embryonic serotonergic (5-HT) neurons and dopamine neurons, we studied the effects of 5-HT in co-cultures of E14 raphe neurons of mesencephalic dopamine neurons and radial glia/astrocytes derived from the same (homotypic) or opposite (heterotypic) brain region using a dose (10(-5) M) that would produce 5-HT uptake into glial cells as well as activate 5-HT receptors. Morphometric analysis of 5-HT and tyrosine hydroxylase (TH) immunoreactive neurons revealed regional differences in the effects of 5-HT (and nialamide) on survival, cell soma size, and dendrite-like neurite outgrowth in neuronal-glial co-cultures. In general, 5-HT had more significant effects on both types of monoamine neuron when they were cultured with mesencephalic glia (GSN). Stimulatory effects of 5-HT on growth of TH neurons in GSN cultures suggest that developing raphe axons, which reach the mesencephalon during the early differentiation of these neurons, may enhance the influence of local glial-derived trophic factors. Likewise, the promotion of 5-HT neuronal survival in these cultures suggests that glial factors in the mesencephalon may contribute to the support of 5-HT neurons in addition to the influences of raphe glia. The inhibitory effects of 5-HT on neurite outgrowth by raphe neurons in GSN co-cultures indicates enhanced sensitivity of these neurons to the inhibitory effects of 5-HT in the presence of mesencephalic glia. The region-specific effects of 5-HT and nialamide in glial co-cultures suggest that raphe and mesencephalic glia may express different capacities for 5-HT uptake, receptors, and/or monoamine oxidase (MAO) activities. These characteristics could be important for the specificity of growth-regulatory influences of glial cells on the development of brain monoamine neurons.

Animals

S-100 beta and insulin-like growth factor-II differentially regulate growth of developing serotonin and dopamine neurons in vitro.

To study the phenotypic specificity of S-100 beta and insulin-like growth factor II (IGF-II) for developing monoamine neurons, serotonin (5-HT) neurons from the embryonic day 14 (E14) rostral raphe or dopamine (TH) neurons from the substantia nigra/ventral tegmental area were cultured for 3 days in vitro (3 DIV) in the presence of these factors. Neuronotrophic effects were analyzed by computer-assisted morphometry of 5-HT and TH-immunoreactive neurons. S-100 beta and IGF-II differentially regulated the growth of 5-HT and TH neurons but did not affect their survival. S-100 beta significantly increased several parameters of neurite outgrowth by 5-HT neurons but inhibited the spatial extent (field area) of TH neurites. IGF-II promoted growth of cell bodies of both phenotype, but only stimulated neurite outgrowth by TH neurons. S-100 beta and IGF-II differentially affected the number of GFAP immunoreactive cells from raphe and substantia nigra, but these effects did not correlate with the specificity of neuronotrophic effects. S-100 beta and IGF-II immunoreactivities were expressed in glial cultures derived from the same brain regions, raising the possibility that these factors have autocrine effects on glia as well as paracrine actions on neurons. The results of this study suggest that specificity of neurotrophic factors for particular embryonic neurons may be correlated with their neurotransmitter phenotype.

Animals

Serotonin as a regulator of craniofacial morphogenesis: site specific malformations following exposure to serotonin uptake inhibitors.

During craniofacial development in the mouse embryo (days 9-12 of gestation; plug day = day 1), transient expression of serotonin (5-HT) uptake in epithelial structures of this region correlates with critical morphogenetic events (Lauder et al., '88; Shuey, '91; Shuey et al., '89, '92). The purpose of the present investigation was to assess the possible functional significance of these uptake sites by examination of patterns of dysmorphology following exposure of embryos to selective 5-HT uptake inhibitors. Exposure of mouse embryos in whole embryo culture to sertraline, at a concentration (10 microM) which produced no evidence of general embryotoxicity, caused craniofacial malformations consistent with direct action at 5-HT uptake sites. Two other 5-HT uptake inhibitors, fluoxetine and amitriptyline, produced similar defects. The critical period of sertraline exposure occurred on days 10-11. The observed craniofacial defects were associated with decreased proliferation and extensive cell death in mesenchyme located 5-6 cell layers deep from the overlying epithelium. In contrast, the subepithelial mesenchymal layers showed normal or elevated levels of proliferation. From these results it appears that inhibition of 5-HT uptake into craniofacial epithelia may produce developmental defects by interference with serotonergic regulation of epithelial-mesenchymal interactions important for normal craniofacial morphogenesis.

1-Naphthylamine

Ontogeny of glucagon messenger RNA in the rat pancreas.

The synthesis of proglucagon mRNA was studied in rat pancreas from day 11 of fetal gestation (E11) to maturity. Proglucagon mRNA was first detected on E11, the time that the pancreatic bud forms in developing rats. The synthesis of proglucagon mRNA and its translation product at this early time point in pancreatic development suggests an early differentiation of A cell function. Between E17 prenatally and day 10-14 postnatally, pancreatic proglucagon mRNA abundance was higher than in adult pancreas. Regulation of the abundance of pancreatic proglucagon mRNA therefore appears to underlie the previously documented increases in serum and pancreatic glucagon immunoreactivity in the late fetal and perinatal periods. By day 20 postnatally, pancreatic proglucagon mRNA declined to levels found in adult pancreas. Prenatally between E17 and E21, changes in proglucagon mRNA abundance did not parallel previously reported developmental changes in relative mass of proglucagon-producing pancreatic A cells. This suggests that changes in proglucagon mRNA abundance during these times may be attributed to changes in proglucagon gene transcription or proglucagon mRNA stability per cell. In contrast between E21 and maturity, changes in proglucagon mRNA abundance paralleled previously reported changes in relative A cell mass, suggesting no major changes in proglucagon gene transcription or mRNA stability per cell during these times.

Animals

Serotonin and nialamide differentially regulate survival and growth of cultured serotonin and catecholamine neurons.

In this morphometric analysis of immunoreactive serotonin (5-HT) and tyrosine hydroxylase (TH) neurons in culture, 5-HT and the MAO inhibitor nialamide influenced the survival, cell body size and neurite outgrowth of embryonic day 14 (E14) 5-HT neurons after treatment from 1-3 days in vitro (DIV), but did not significantly affect E14 or E15 TH neurons of either the noradrenergic or dopaminergic phenotype. These treatments had minimal effects on 5-HT neurons derived from E15 embryos. The stimulatory effects of 5-HT on survival and somal growth of E14 5-HT neurons was in contrast to its inhibitory effects on neurite outgrowth, suggesting trophic and inhibitory autoregulation of different cellular compartments of developing 5-HT neurons. The decreased sensitivity of E15 5-HT neurons to these treatments, despite similar viability and growth of these neurons in control cultures, suggests the existence of a critical period for this regulation during the initial period of serotonergic neurogenesis when these neurons are forming the bilateral B4-9 raphe complex. The lack of significant effects of 5-HT on TH neurons suggests differential sensitivities of 5-HT and TH neurons to developmental regulation by this neurotransmitter.

Animals

An atlas of the prenatal mouse brain: gestational day 14.

A prenatal atlas of the mouse brain is presently unavailable and is needed for studies of normal and abnormal development, using techniques including immunocytochemistry and in situ hybridization. This atlas will be especially useful for researchers studying transgenic and mutant mice. This collection of photomicrographs and corresponding drawings of Gestational Day (GD) 14 mouse brain sections is an excerpt from a larger atlas encompassing GD 12-18. In composing this atlas, available published studies on the developing rodent brain were consulted to aid in the detailed labeling of embryonic brain structures. C57Bl/6J mice were mated for 1 h, and the presence of a copulation plug was designated as GD 0. GD 14 embryos were perfused transcardially with 4% paraformaldehyde in 0.1 M phosphate buffer and embedded in paraffin. Serial sections (10 microns thickness) were cut through whole heads in sagittal and horizontal planes. They were stained with hematoxylin and eosin and photographed. Magnifications were 43X and 31X for the horizontal and sagittal sections, respectively. Photographs were traced and line drawings prepared using an Adobe Illustrator on a Macintosh computer.

Animals

Neuronal-glial interactions: complexity of neurite outgrowth correlates with substrate adhesivity of serotonergic neurons.

To study the interactions between neurons of known transmitter phenotype and non-neuronal cells of glial or fibroblastic origin, serotonergic (5-HT) neurons were tested for their strength of adhesion and neurite outgrowth patterns on substrates of astrocytes or fibroblasts using a cell adhesion assay for transmitter-identified neurons, and morphometry of immunocytochemically stained neurons in dissociated cell cultures. Both the strength of adhesion and the rate and complexity of neurite outgrowth by 5-HT neurons were significantly greater on substrates of astrocytes compared to fibroblasts. These results provide evidence that 5-HT neurons can interact selectively with glia via cell surface determinants, and that this process may be important for the development of complex (dendrite-like) neuritic arbors. The methods developed in this study will be useful for future studies of interactions between transmitter-identified neurons and glial cells during ontogeny of the embryonic brain.

Animals

Development of neurotransmitter systems in the mouse embryo following acute ethanol exposure: a histological and immunocytochemical study.

Acute maternal ethanol administration to C57B1/6J mice on gestational day 7 (GD7) results in facial and brain abnormalities similar to those reported in human fetal alcohol syndrome (FAS). Using this model, we assessed the damage to brain structures using histological methods and changes in developing neurotransmitter systems with immunocytochemistry. Cholinergic neurons in the forebrain were stained with a monoclonal antibody to choline acetyltransferase (ChAT). Catecholaminergic neurons in the midbrain and serotoninergic neurons in the hindbrain were stained with polyclonal antisera to tyrosine hydroxylase (TH) and serotonin (5-HT), respectively. Forebrain deficiencies, including loss of midline structures (olfactory bulbs, midline septation, medial septal area) and deficits in lateral and dorsal regions (neostriatum and cerebral cortex) were found in both GD14 embryos and GD18 fetuses. In severely affected offspring, complete loss of the septal region resulted in conjoined lateral ventricles and a reduction in the thickness of the ventricular zone surrounding the single ventricle, as well as a severe loss of ChAT neurons which would normally be located in this territory. However, no consistent changes were seen in the distribution or size of TH or 5-HT neuronal cell groups in the midbrain and hindbrain. These differences in effects on specific neurotransmitter systems reflect the fact that the forebrain is most severely affected by early ethanol administration, whereas the hindbrain is relatively spared. Such differential effects could produce an imbalance in developing neurotransmitter systems in the embryonic and fetal brain, which could explain some of the functional deficits observed in children with FAS.

Abnormalities, Drug-Induced

Ontogeny of the serotonergic system in the rat: serotonin as a developmental signal.

The serotonergic system is an early forming component of the CNS circuitry, beginning its development on gestational days 11-12 in the rat. Owing to its early presence in the embryonic nervous system, 5-HT has been proposed to act as a developmental signal for receptive cells. In vivo and in vitro evidence that 5-HT can influence both biochemical and morphological differentiation of raphe neurons and receptive target cells suggests that this neurotransmitter may have an organizing function in the developing nervous system which involves effects on neurite outgrowth and other aspects of neuronal differentiation, including synaptogenesis. Such functions may be mediated by a variety of 5-HT receptors located on both neuronal and non-neuronal cells. The apparent function of 5-HT as a differentiation signal in the developing nervous system raises important issues regarding the use of psychoactive serotonergic drugs by pregnant women, since these drugs may act as neural teratogens in the unborn child.

Aging

Ontogeny of cholinergic neurons in the mouse forebrain.

The development of cholinergic neurons in the mouse forebrain was studied by immunocytochemistry with a monoclonal antibody to choline acetyltransferase (ChAT), the rate-limiting enzyme for acetylcholine synthesis. Since this antibody stained dividing cells in ventricular germinal zones as well as differentiating neurons, likely routes of migration could be inferred on the basis of the location of immunoreactive (IR) cells at different gestational ages. Germinal zones for cholinergic cells were observed in all ventricular zones of the forebrain with the ventral zones generating the earliest cells by gestational day 13.5 (GD13.5). On GD14, ChAT IR cells were visible in the germinal zones of the eye, olfactory ventricle, anterior horn, and dorsolateral aspect of the lateral ventricle, lateral ganglionic eminence, ventro- and dorsolateral third ventricle, and in the pineal anlage (epiphysis). ChAT IR neurons continued to develop in these and additional germinal zones on GD15, including the medial, dorsal, and dorsomedial walls of the lateral ventricle, and the medial and dorsal ganglionic eminence. On GD16, ChAT IR neurons were located in the prelimbic, pyriform, and parietal cortices and the lamina terminalis, and a cluster of IR cells was observed in the ventricular zone of the caudatopallial angle. On GD17-18, neurons in the anterior olfactory nucleus, olfactory tubercle, horizontal and vertical nucleus of the diagonal band, and medial septal nucleus stained more darkly and were multipolar, whereas immature bipolar neurons appeared to continue their migration into the hippocampus and along major fiber tracts, such as the corpus callosum, external capsule, fornix and anterior commissure. This study provides a comprehensive view of the zones of origin, probable routes of migration, and final destination of cholinergic neurons in the mouse forebrain.

Aging

Neuronal-glial interactions: quantitation of astrocytic influences on development of catecholamine neurons.

Effects of astroglia on the morphological and biochemical differentiation of catecholamine neurons from embryonic rat mesencephalon were studied in vitro, and compared to results obtained with fibroblasts. Neurite outgrowth and complexity were measured using computer-assisted morphometry on tyrosine hydroxylase immunoreactive neurons growing on preformed monolayers of astrocytes or fibroblasts. The morphological differentiation of these neurons was stimulated by the presence of astrocytes, and this effect was evident in various cellular compartments, including the size of the cell soma, length of neurites and neuritic segments, and the numbers of these segments. Tyrosine hydroxylase activity was measured biochemically in these cultures and was also found to be stimulated by the presence of astroglial monolayers. The implication of these results for the understanding of specific neuron-glial interactions during embryonic brain development is discussed.

Animals

Serotonergic innervation of the rat caudate following a neonatal 6-hydroxydopamine lesion: an anatomical, biochemical and pharmacological study.

6-Hydroxydopamine (6-OHDA) treatment of neonatal rats resulted in a dose-related loss of striatal dopamine (DA). These reductions corresponded closely with the loss of tyrosine hydroxylase-containing terminals at this brain site. Striatal serotonin (5-HT) concentration increased only after DA was maximally depleted by the highest dose of 6-OHDA. Quantitative immunohistochemistry revealed that the increased 5-HT content after neonatal 6-OHDA lesioning was due to a proliferation of 5-HT nerve terminals. The density of immunoreactive 5-HT-containing terminals appeared to increase more than did the 5-HT content. The present study examined whether 5-HT hyperinnervation was playing a role in behavioral responses induced by D1-DA agonists and antagonists in neonatally lesioned rats, because reports have suggested that these drugs may interact with 5-HT receptors. However, SCH-23390, the D1-DA antagonist (0.3 mg/kg), did not alter behavioral responses to 5-HTP and SKF-38393 (3 mg/kg), a D1-DA agonist did not produce any signs of activating 5-HT receptors in 5,7-DHT-lesioned rats. These data indicate that these compounds affecting D1-DA receptors do not have a significant effect on 5-HT function at doses which have maximal effects on D1-DA receptor function. Pretreatment with the 5-HT antagonist methysergide did not produce a change in apomorphine-induced locomotion and did not antagonize the self-mutilation or the other behaviors produced by L-DOPA or SKF-38393 in neonatally lesioned rats, suggesting that 5-HT hyperinnervation is not responsible for these drug-induced changes in neonatal 6-OHDA-lesioned rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Development and distribution of serotonin in the central nervous system of Manduca sexta during embryogenesis. I. The brain and frontal ganglion.

Development of the serotonergic system in the brain and frontal ganglion of the Manduca embryo between 35 and 100% of development was studied immunocytochemically with an antiserum to serotonin (5-HT). Serotonin immunoreactivity was initially detectable at 40-45% development in short fibers in the head region, prior to differentiation of the brain. Immunoreactive cell bodies were first seen in the brain at 60% development, located in the protocerebrum and tritocerebrum. Thick fiber tracts crossing the midline (commissures) could also be observed at this early stage. As development of the embryo progressed, eight immunoreactive cell groups, containing a total of about 38-40 cells, and four commissures with terminal arborizations appeared successively in the brain. From 75 to 100% development, no obvious changes occurred in the number or distribution of cells, and the brain exhibited the same pattern of 5-HT immunoreactive cells, fiber tracts and arborizations as in last instar larvae of Manduca. However, an increase in the size of the cells in both the brain and frontal ganglion was noted between 75 and 80% development, followed by a decrease by 100% development. The frontal ganglion was found to contain three 5-HT immunoreactive cells, which appeared to send bilateral projections into the frontal connectives and the recurrent nerve. During embryonic development, the dendritic arborizations of these frontal ganglion cells increased, while the amount of 5-HT immunoreactivity in the cell bodies decreased. Thus, the serotonergic system first appears in the Manduca embryo at an early stage of development, similar to the situation in other insects as well as vertebrates. By the end of the embryonic period, the same number of serotonergic neurons are present in the brain as in larval and adult Manduca, suggesting that once formed, these cells persist through postembryonic development and metamorphosis.

Animals

Development and distribution of serotonin in the central nervous system of Manduca sexta during embryogenesis. II. The ventral ganglia.

The distribution of serotonin (5-HT) immunoreactive cells and their projections was mapped in the ganglia of the ventral nerve cord of the tobacco hornworm, Manduca sexta, during embryonic development, using an antiserum to 5-HT. Immunoreactive cells were first seen at 60% development. By 75% of embryonic development, a total of 94 immunoreactive cells were found in the ventral ganglia, including the suboesophageal ganglion. This number decreased to 80 neurons by 100% of development. About 50% of these cells were arranged in the abdominal ganglia and the rest were located in both the suboesophageal and thoracic ganglia. The suboesophageal ganglion exhibited immunoreactive segmental interneurons in areas corresponding to the mandibular, maxillary and labial neuromeres. Two pairs of immunoreactive interneurons were also observed to occur bilaterally in each of the thoracic and abdominal ganglia, with the exception of the prothoracic ganglion. This ganglion contained three pairs of bilaterally arranged immunoreactive neurons as early as 60% of embryonic development. Serotonin immunoreactivity was also found in a number of efferent neurons in the mandibular and labial neuromeres of the suboesophageal ganglion and in the prothoracic, mesothoracic and posterior abdominal ganglia. The occurrence of 5-HT in these efferent neurons suggests an involvement of serotonin in fore- and hindgut function via its effect on the visceral muscles. Immunoreactive lateral longitudinal fibers extended along the entire length of the ventral nerve cord together with dense segmental arborizations. The latter had regressed by the time the embryo was fully developed. This regression of the arborizations in the ganglia at the end of embryonic development indicates that a reorganization of 5-HT innervation occurs to support new larval functions. The time of appearance of 5-HT immunoreactive cells and fibers suggests that serotonin may play a role in the development of the ventral nerve cord.

Animals

Serotonin-immunoreactive neurons in the brain of Manduca sexta during larval development and larval-pupal metamorphosis.

The developing serotonergic system of the tobacco hornworm, Manduca sexta, has been studied immunocytochemically in whole mount preparations of brain-retrocerebral complexes. The distribution of serotonin-immunoreactive cell bodies, fibers and terminal fields has been analysed during larval and larval-pupal development using a specific rabbit antiserum against serotonin-hemocyanin conjugates. The serotonergic system was conserved from the fourth to the fifth larval stadium, with minimal changes occurring until the onset of pupal development. At this time, alterations in the distribution of serotonin-immunoreactive cells and processes were observed, including the apparent disappearance of some cell bodies and terminals. Nevertheless, the overall appearance of this system in the pupal brain was not significantly different from that in the larva. The larval pattern was characterized by eight bilateral groups of cell bodies which sent thick bridges of fibers across the midline, a feature strikingly similar to the serotonergic system in vertebrate embryos. In addition, three bilateral immunoreactive fields of arborization were observed around and ventral to these cell groups, together with regions of serotonin immunoreactivity in the medial and lateral protocerebral lobes. The central body, larval antennal centers, larval accessory lobes, and the tritocerebrum were also immunoreactive. Fibrous networks of serotonergic processes were usually observed around nerves emanating from the brain, including the connectives from the brain to the corpus cardiacum and corpus allatum. Smaller varicosities were observed in the interior of these neurohemal and glandular organs, and a network of 5-HT fibers was occasionally found around the corpus cardiacum and corpus allatum. The possible relationship of serotonin to cerebral neuroendocrine functions during the postembryonic development of M. sexta is discussed.

Animals

Distribution of glucagonlike peptide I (GLP-I), glucagon, and glicentin in the rat brain: an immunocytochemical study.

Although glucagonlike immunoreactants (GLIs) are present in the central nervous system of several mammalian species, their structural relationship with pancreatic proglucagon is not defined, and their precise anatomical distribution has not been studied extensively. To obtain further information about the structure and biological significance of brain GLIs, the anatomical distribution of three different antigenic determinants of pancreatic proglucagon--glucagonlike peptide I (GLP-I), glucagon, and glicentin--was mapped in the brain of colchicine-treated rats by immunocytochemistry using the avidin-biotin-peroxidase method. Neuronal cell bodies immunoreactive with antisera specific for GLP-I, glucagon, and glicentin were found only in the caudal medulla oblongata. Within the caudal medulla immunostained cell bodies were found at levels from approximately 0.55 mm rostral to the obex to 0.45 mm caudal to the obex, and were located within the nucleus of the solitary tract (NTS) and the dorsal (MdD) and ventral (MdV) parts of the medullary reticular nucleus. The NTS contained three times more immunoreactive cell bodies than the MdD and MdV, and these cell bodies were located in the midline, medial, and lateral subnuclei of the caudal third of the NTS. Immunostaining of the same cell bodies in paired adjacent sections incubated with GLP-I and glucagon antisera or glucagon and glicentin antisera provided evidence for coexistence of the three antigens within the same neurons of the NTS. Nerve fibers and terminals immunoreactive with GLP-I, glucagon, and glicentin antisera were widely distributed throughout the rat brain and there was no discernible difference in the distribution of fibers and terminals immunoreactive with each of the three antisera. The highest densities of immunostained fibers and terminals were observed in the hypothalamus, thalamus, and septal regions, and the lowest in the cortex and hindbrain. The localization of neuronal cell bodies containing GLP-I, glucagon, and glicentin within the NTS and the MdD and MdV, and the extensive distribution of immunoreactive fibers and terminals throughout the rat brain suggest a role for these peptides in the integration of autonomic as well as central nervous system functions.

Animals

Tyrosine hydroxylase and serotonin containing cells in embryonic rat rhombencephalon: a whole-mount immunocytochemical study.

Rhombencephala from rat embryos were processed as whole-mounts for immunocytochemical detection of monoaminergic cell populations, using antibodies to tyrosine hydroxylase (TH) and serotonin (5-HT). Specific advantages of the whole-mount technique over the classical serial-section method were that even isolated immunoreactive (IR) cells could be detected easily, and three-dimensional relationships could be ascertained without the need for serial reconstruction. Embryos between embryonic days (E) 12 and 16 (the day following nocturnal mating being considered as E1) were used in this study. Both TH and 5-HT immunoreactivities were already detectable at E12, even in the smallest embryos (crown-rump length: 6 mm), but there was a striking difference in the number and regional distribution of these two types of IR cells. TH was expressed in several cell groups located in the rostral rhombencephalon (the presumed anlage of the A4-7 complex) as well as in the caudal rhombencephalon (the presumed anlagen of groups A1-2 and C1-3), whereas 5-HT was expressed in very few cells located near the rostral border of the rhombencephalon (presumed anlage of the B4-9 complex). Although the three-dimensional distribution of the TH-IR cell groups underwent some modifications during the period studied, its general pattern remained relatively stable after E12. This contrasted with the sequential appearance of the 5-HT-IR cell groups and their spatial transformations during this period. Using the rhombencephalic isthmus as a landmark, we found that conspicuous 5-HT-IR fibre bundles penetrated into the mesencephalon from E13 onwards, but that the 5-HT IR cell bodies were exclusively located caudal to the borderline between the mesencephalon and the rhombencephalon (the rhombencephalic isthmus). We therefore suggest the term "rostral rhombencephalic raphe nuclei" for the rostral 5-HT cell groups instead of "mesencephalic raphe nuclei," which is a misnomer. Close spatial association between TH and 5-HT-IR elements was observed mainly in the caudal rhombencephalon, where 5-HT-IR fibres coursed through an area containing numerous TH-IR cell bodies (the presumed anlagen of groups A1-2 and C1-3).

Animals