RESUMO
BACKGROUND: The neurons contributing to thalamic nuclei are derived from at least two distinct progenitor domains: the caudal (cTH) and rostral (rTH) populations of thalamic progenitors. These neural compartments exhibit unique neurogenic patterns, and the molecular mechanisms underlying the acquisition of neurotransmitter identity remain largely unclear. RESULTS: T-cell acute lymphocytic leukemia protein 1 (Tal1) was expressed in the early postmitotic cells in the rTH domain, and its expression was maintained in mature thalamic neurons in the ventrolateral geniculate nucleus (vLG) and the intergeniculate leaflet (IGL). To investigate a role of Tal1 in thalamic development, we used a newly generated mouse line driving Cre-mediated recombination in the rTH domain. Conditional deletion of Tal1 did not alter regional patterning in the developing diencephalon. However, in the absence of Tal1, rTH-derived thalamic neurons failed to maintain their postmitotic neuronal features, including neurotransmitter profile. Tal1-deficient thalamic neurons lost their GABAergic markers such as Gad1, Npy, and Penk in IGL/vLG. These defects may be associated at least in part with down-regulation of Nkx2.2, which is known as a critical regulator of rTH-derived GABAergic neurons. CONCLUSIONS: Our results demonstrate that Tal1 plays an essential role in regulating neurotransmitter phenotype in the developing thalamic nuclei. Developmental Dynamics 246:749-758, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Neurotransmissores , Proteína 1 de Leucemia Linfocítica Aguda de Células T/fisiologia , Núcleos Talâmicos/citologia , Animais , Proteína Homeobox Nkx-2.2 , Camundongos , Células-Tronco , Núcleos Talâmicos/embriologia , Tálamo/citologia , Tálamo/embriologiaRESUMO
Comparative embryonic studies are the most effective way to discern phylogenetic changes. To gain insight into the constitution and evolution of mammalian somatosensory thalamic nuclei, we first studied how calbindin (CB) and parvalbumin (PV) immunoreactivities appear during embryonic development in the first-order relaying somatosensory nuclei, i.e., the ventral posteromedial (VPM) and posterolateral (VPL) nuclei, and their neighboring higher-order modulatory regions, including the ventromedial or ventrolateral nucleus, posterior, and the reticular nucleus. The results indicated that cell bodies that were immunoreactive for CB were found earlier (embryonic day 12 [E12]) in the dorsal thalamus than were cells positive for PV (E14), and the adult somatosensory thalamus was characterized by complementary CB and PV distributions with PV dominance in the first-order relaying nuclei and CB dominance in the higher-order regions. We then labeled proliferating cells with [(3) H]-thymidine from E11 to 19 and found that the onset of neurogenesis began later (E12) in the first-order relaying nuclei than in the higher-order regions (E11). Using double-labeling with [(3) H]-thymidine autoradiography and CB or PV immunohistochemistry, we found that CB neurons were born earlier (E11-12) than PV neurons (E12-13) in the studied areas. Thus, similar to auditory nuclei, the first and the higher-order somatosensory nuclei exhibited significant distinctions in CB/PV immunohistochemistry and birthdates during embryonic development. These data, combined with the results of a cladistic analysis of the thalamic somatosensory nuclei, are discussed from an evolutionary perspective of sensory nuclei.
Assuntos
Calbindinas/metabolismo , Neurogênese , Parvalbuminas/metabolismo , Núcleos Talâmicos/citologia , Núcleos Talâmicos/metabolismo , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Autorradiografia , Embrião de Mamíferos , Camundongos , Neurônios , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/crescimento & desenvolvimento , Timidina/metabolismo , Trítio/metabolismoRESUMO
The modification of the neural cell adhesion molecule (NCAM) with polysialic acid (polySia) is tightly linked to neural development. Genetic ablation of the polySia-synthesizing enzymes ST8SiaII and ST8SiaIV generates polySia-negative but NCAM-positive (II(-/-)IV(-/-)) mice characterized by severe defects of major brain axon tracts, including internal capsule hypoplasia. Here, we demonstrate that misguidance of thalamocortical fibers and deficiencies of corticothalamic connections contribute to internal capsule defects in II(-/-)IV(-/-) mice. Thalamocortical fibers cross the primordium of the reticular thalamic nucleus (Rt) at embryonic day 14.5, before they fail to turn into the ventral telencephalon, thus deviating from their normal trajectory without passing through the internal capsule. At postnatal day 1, a reduction and massive disorganization of fibers traversing the Rt was observed, whereas terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved caspase-3 staining indicated abundant apoptotic cell death of Rt neurons at postnatal day 5. Furthermore, during postnatal development, the number of Rt neurons was drastically reduced in 4-week-old II(-/-)IV(-/-) mice, but not in the NCAM-deficient N(-/-) or II(-/-)IV(-/-)N(-/-) triple knock-out animals displaying no internal capsule defects. Thus, degeneration of the Rt in II(-/-)IV(-/-) mice may be a consequence of malformation of thalamocortical and corticothalamic fibers providing major excitatory input into the Rt. Indeed, apoptotic death of Rt neurons could be induced by lesioning corticothalamic fibers on whole-brain slice cultures. We therefore propose that anterograde transneuronal degeneration of the Rt in polysialylation-deficient, NCAM-positive mice is caused by defective afferent innervation attributable to thalamocortical pathfinding defects.
Assuntos
Córtex Cerebral/patologia , Neurônios/patologia , Ácidos Siálicos/genética , Tálamo/patologia , Vias Aferentes/anormalidades , Animais , Animais Recém-Nascidos , Apoptose , Axônios/patologia , Córtex Cerebral/embriologia , Córtex Cerebral/crescimento & desenvolvimento , Dopamina/metabolismo , Cápsula Interna/anormalidades , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibras Nervosas/patologia , Moléculas de Adesão de Célula Nervosa/genética , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/crescimento & desenvolvimento , Núcleos Talâmicos/patologia , Tálamo/embriologia , Tálamo/crescimento & desenvolvimentoRESUMO
The establishment of connectivity between specific thalamic nuclei and cortical areas involves a dynamic interplay between the guidance of thalamocortical axons and the elaboration of cortical areas in response to appropriate innervation. We show here that Sema6A mutants provide a unique model to test current ideas on the interactions between subcortical and cortical guidance mechanisms and cortical regionalization. In these mutants, axons from the dorsal lateral geniculate nucleus (dLGN) are misrouted in the ventral telencephalon. This leads to invasion of presumptive visual cortex by somatosensory thalamic axons at embryonic stages. Remarkably, the misrouted dLGN axons are able to find their way to the visual cortex via alternate routes at postnatal stages and reestablish a normal pattern of thalamocortical connectivity. These findings emphasize the importance and specificity of cortical cues in establishing thalamocortical connectivity and the spectacular capacity of the early postnatal cortex for remapping initial sensory representations.
Assuntos
Axônios/fisiologia , Plasticidade Neuronal/fisiologia , Semaforinas/metabolismo , Núcleos Talâmicos/embriologia , Tálamo/embriologia , Córtex Visual/embriologia , Vias Visuais/embriologia , Animais , Feminino , Corpos Geniculados/embriologia , Corpos Geniculados/fisiologia , Camundongos , Camundongos Knockout , Telencéfalo/embriologia , Telencéfalo/fisiologia , Núcleos Talâmicos/fisiologia , Tálamo/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologiaRESUMO
The mammalian thalamus is located in the diencephalon and is composed of dozens of morphologically and functionally distinct nuclei. The majority of these nuclei project axons to the neocortex in unique patterns and play critical roles in sensory, motor, and cognitive functions. It has been assumed that the adult thalamus is derived from neural progenitor cells located within the alar plate of the caudal diencephalon. Nevertheless, how a distinct array of postmitotic thalamic nuclei emerge from this single developmental unit has remained largely unknown. Our recent studies found that these thalamic nuclei are in fact derived from molecularly heterogeneous populations of progenitor cells distributed within at least two distinct progenitor domains in the caudal diencephalon. In this study, we investigated how such molecular heterogeneity is established and maintained during early development of the thalamus and how early signaling mechanisms influence the formation of postmitotic thalamic nuclei. By using mouse genetics and in utero electroporation, we provide evidence that Sonic hedgehog (Shh), which is normally expressed in ventral and rostral borders of the embryonic thalamus, plays a crucial role in patterning progenitor domains throughout the thalamus. We also show that increasing or decreasing Shh activity causes dramatic reorganization of postmitotic thalamic nuclei through altering the positional identity of progenitor cells.
Assuntos
Proteínas Hedgehog/fisiologia , Transdução de Sinais/fisiologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Tálamo/citologia , Tálamo/fisiologia , Animais , Feminino , Proteínas Hedgehog/biossíntese , Proteínas Hedgehog/deficiência , Proteínas Hedgehog/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Gravidez , Núcleos Talâmicos/citologia , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/fisiologia , Tálamo/embriologiaRESUMO
Mice with mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein-6 (LRP6) have a smaller and severely disorganized dorsal thalamus and lack thalamocortical projections. Using molecular markers, we showed that most dorsal thalamic and epithalamic neurons were missing, and most of the major dorsal thalamic nuclei were not identifiable. However, the ventral thalamus was essentially unaffected, although the dorsal thalamic defect leads to rostral displacement of portions of the ventral thalamus. Analysis of younger embryos showed that epithalamic and dorsal thalamic neurons were not produced at early stages of development, whereas ventral thalamic neurons were still produced. These defects were accompanied by improper formation of the boundary between dorsal and ventral thalamus, the zona limitans interthalamica (ZLI). Furthermore, the expression of an early marker of posterior forebrain development that marks the compartment from the midbrain-hindbrain junction to the ZLI (including the future dorsal thalamus, pretectum, and midbrain) was disrupted, supporting the idea that diencephalic development is abnormal from very early in embryogenesis. This study provides compelling in vivo evidence that thalamic development requires normal activity of the LRP6-mediated canonical Wnt signaling pathway.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Receptores de LDL/fisiologia , Tálamo/embriologia , Animais , Proteínas do Citoesqueleto/fisiologia , Diencéfalo/anormalidades , Diencéfalo/embriologia , Idade Gestacional , Proteínas Hedgehog , Proteínas Relacionadas a Receptor de LDL , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Camundongos , Camundongos Knockout , Morfogênese , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/fisiologia , Receptores de LDL/deficiência , Receptores de LDL/genética , Transdução de Sinais/fisiologia , Núcleos Talâmicos/anormalidades , Núcleos Talâmicos/embriologia , Tálamo/anormalidades , Transativadores/análise , Transativadores/deficiência , Transativadores/fisiologia , Proteínas Wnt , Proteína Wnt-5a , beta CateninaRESUMO
The distribution of the CD15 antigen (CD15, 3-fucosyl-N-acetyl-lactosamine, Lewis x) has been studied immunohistochemically in the fetal human thalamus. Its changing patterns could be related to three successive, but overlapping, periods primarily due to its association with radial glial cells, neuropil, and neural cell bodies, respectively. From 9 weeks of gestation (wg), a subset of CD15-positive radial glial cells distinguished the neuroepithelium of the ventral thalamus, a characteristic also seen in the developing mouse. Distal processes of the radial glial cells converged at the root of the forebrain choroid tenia, which was also CD15 positive. From 13 wg until approximately 20 wg, CD15-positive neuropil labeling marked the differentiation areas of prospective nuclei within the dorsal thalamus and progressively outlined their territories in a time sequence, which appeared specific for each nucleus. CD15 labeling of differentiating nuclei of the ventral, medial, anterior, and intralaminar thalamic divisions showed a transient topographic relationship with restricted areas of the ventricular wall. After 26 wg, CD15 immunoreactivity was observed in subpopulations of glial cells and neurons. Transient CD15 immunoreactivity was also found in delimited compartments within the subventricular region. The time of CD15 expression, its location, and cellular association suggest that CD15 is involved in segmentation of diencephalon, in the specification of differentiating nuclear areas and initial processes regarding the formation of intercellular contacts and cellular maturation.
Assuntos
Antígenos CD15/análise , Proteínas do Tecido Nervoso/análise , Tálamo/anatomia & histologia , Biomarcadores , Calbindina 2 , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Humanos , Recém-Nascido , Antígenos CD15/biossíntese , Antígenos CD15/genética , Morfogênese , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Neuroglia/química , Neurônios/química , Neurópilo/química , Proteína G de Ligação ao Cálcio S100/análise , Núcleos Talâmicos/anatomia & histologia , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/crescimento & desenvolvimento , Tálamo/embriologia , Tálamo/crescimento & desenvolvimentoRESUMO
Many neurons die as the normal brain develops. How this is regulated and whether the mechanism involves neurotrophic molecules from target cells are unknown. We found that cultured neurons from a key forebrain structure, the dorsal thalamus, develop a need for survival factors including brain-derived neurotrophic factor (BDNF) from their major target, the cerebral cortex, at the age at which they innervate it. Experiments in vivo have shown that rates of dorsal thalamic cell death are reduced by increasing cortical levels of BDNF and are increased in mutant mice lacking functional BDNF receptors or thalamocortical projections; these experiments have also shown that an increase in the rates of dorsal thalamic cell death can be achieved by blocking BDNF in the cortex. We suggest that the onset of a requirement for cortex-derived neurotrophic factors initiates a competitive mechanism regulating programmed cell death among dorsal thalamic neurons.
Assuntos
Fatores de Crescimento Neural/metabolismo , Neurônios/metabolismo , Prosencéfalo/metabolismo , Animais , Anticorpos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Meios de Cultivo Condicionados/farmacologia , Proteínas do Olho , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Knockout , Fatores de Crescimento Neural/antagonistas & inibidores , Fatores de Crescimento Neural/farmacologia , Vias Neurais/citologia , Vias Neurais/embriologia , Vias Neurais/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados , Prosencéfalo/citologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/embriologia , Receptor trkB/deficiência , Receptor trkB/genética , Receptor trkC/deficiência , Receptor trkC/genética , Receptores de Fator de Crescimento Neural/deficiência , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/metabolismo , Proteínas Repressoras , Núcleos Talâmicos/citologia , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/metabolismo , Tálamo/citologia , Tálamo/efeitos dos fármacos , Tálamo/embriologia , Tálamo/metabolismoRESUMO
The anatomical and functional organization of dorsal thalamus (dTh) and ventral thalamus (vTh), two major regions of the diencephalon, is characterized by their parcellation into distinct cell groups, or nuclei, that can be histologically defined in postnatal animals. However, because of the complexity of dTh and vTh and difficulties in histologically defining nuclei at early developmental stages, our understanding of the mechanisms that control the parcellation of dTh and vTh and the differentiation of nuclei is limited. We have defined a set of regulatory genes, which include five LIM-homeodomain transcription factors (Isl1, Lhx1, Lhx2, Lhx5, and Lhx9) and three other genes (Gbx2, Ngn2, and Pax6), that are differentially expressed in dTh and vTh of early postnatal mice in distinct but overlapping patterns that mark nuclei or subsets of nuclei. These genes exhibit differential expression patterns in dTh and vTh as early as embryonic day 10.5, when neurogenesis begins; the expression of most of them is detected as progenitor cells exit the cell cycle. Soon thereafter, their expression patterns are very similar to those that we observe postnatally, indicating that unique combinations of these genes mark specific cell groups from the time they are generated to their later differentiation into nuclei. Our findings suggest that these genes act in a combinatorial manner to control the specification of nuclei-specific properties of thalamic cells and the differentiation of nuclei within dTh and vTh. These genes may also influence the pathfinding and targeting of thalamocortical axons through both cell-autonomous and non-autonomous mechanisms.
Assuntos
Genes Reguladores/fisiologia , Proteínas de Homeodomínio/metabolismo , Tálamo/embriologia , Tálamo/metabolismo , Fatores de Transcrição/metabolismo , Animais , Diferenciação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Endogâmicos ICR , Morfogênese/genética , Núcleos Talâmicos/anatomia & histologia , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/metabolismo , Tálamo/anatomia & histologia , Fatores de Transcrição/genéticaRESUMO
This study examines the early organization of glial cells, together with the expression of chondroitin sulfate proteoglycans in the developing thalamus of ferrets. Glia were identified with antibodies against vimentin and glial fibrillary acidic protein and the chondroitin sulfate proteoglycans were identified by using an antibody against chondroitin sulfate side chains. Our results reveal three striking features of early thalamic development. First, there is a distinct population of glial fibrillary acidic protein-immunoreactive astrocytes (first seen at E30) that resides in the perireticular thalamic nucleus of the primordial internal capsule. These glial fibrillary acidic protein-immunoreactive astrocytes of the perireticular nucleus are transient and form a conspicuous feature of the early developing forebrain. They are first apparent well before any glial fibrillary acidic protein-immunoreactive astrocytes are seen in other regions of the thalamus (at about P8). Further, unlike in other thalamic regions, these peculiar perireticular astrocytes do not express vimentin before they express glial fibrillary acidic protein. Second, in the reticular thalamic nucleus, the radial glial cells express glial fibrillary acidic protein; they are the only ones to do so in the thalamus during development. The glial fibrillary acidic protein-immunoreactive radial glial cells of the reticular nucleus form a rather distinct band across the developing thalamus at these early stages (E30-P1). Finally, and preceding the expression of glial fibrillary acidic protein, the radial glial cells of the reticular nucleus, unlike those in other thalamic regions, are associated closely with the expression of chondroitin sulfate proteoglycans (E20-E30). Later (after E30), the expression of the chondroitin sulfate proteoglycans in the reticular nucleus declines sharply. The significance of this finding is related to the early organization of the cortico-fugal and cortico-petal pathways.
Assuntos
Envelhecimento/metabolismo , Proteoglicanas de Sulfatos de Condroitina/biossíntese , Desenvolvimento Embrionário e Fetal , Regulação da Expressão Gênica no Desenvolvimento , Neuroglia/fisiologia , Tálamo/fisiologia , Animais , Biomarcadores , Proteoglicanas de Sulfatos de Condroitina/análise , Furões , Proteína Glial Fibrilar Ácida/análise , Prosencéfalo/embriologia , Prosencéfalo/crescimento & desenvolvimento , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/crescimento & desenvolvimento , Núcleos Talâmicos/fisiologia , Tálamo/embriologia , Tálamo/crescimento & desenvolvimento , Vimentina/análiseRESUMO
How are long-range axonal projections from the cerebral cortex orchestrated during development? By using both passively and actively transported axonal tracers in fetal and postnatal ferrets, we have analyzed the development of projections from the cortex to a number of thalamic nuclei. We report that the projections of a cortical area to its corresponding thalamic nuclei follow highly cell-specific programs of development. Axons from cells in the deepest layers of the cerebral cortex (layer 6 and superficial subplate neurons) appear to grow very slowly and be delayed for several weeks in the cerebral white matter, reaching the thalamus over a protracted period. Neurons of layer 5, on the other hand, develop their projections much faster; despite being born after the neurons of deeper layers, layer 5 neurons are the first to extend their axons out of the cortical hemisphere and innervate the thalamus. Layer 5 projections are massive in the first postnatal weeks but may become partly eliminated later in development, being overtaken in number by layer 6 cells that constitute the major corticothalamic projection by adulthood. Layer 5 projections are area-specific from the outset and arise as collateral branches of axons directed to the brainstem and spinal cord. Our findings show that the early development of corticofugal connections is determined not by the sequence of cortical neurogenesis but by developmental programs specific for each type of projection neuron. In addition, they demonstrate that in most thalamic nuclei, layer 5 neurons (and not subplate or layer 6 neurons) establish the first descending projections from the cerebral cortex.
Assuntos
Córtex Cerebral/embriologia , Núcleos Talâmicos/embriologia , Animais , Transporte Axonal , Axônios/ultraestrutura , Mapeamento Encefálico , Vias Eferentes , Feminino , Furões , Masculino , Tálamo/embriologiaRESUMO
The goal of the present study was to determine whether alterations in neuronal morphology and connections in thalamic grafts were accompanied by changes in the expression of mRNA encoding glutamic acid decarboxylase (GAD), the key enzyme in the synthesis of GABA, the normal neurotransmitter of neurons of the thalamic reticular nucleus. Cell suspensions of rat fetal tissue containing both thalamic reticular nucleus and ventrobasal primordia were transplanted into the excitotoxically lesioned somatosensory thalamus of adult rats. Levels of messenger RNA (mRNA) encoding GAD (Mr 67,000; GAD67) were measured 7 days to 4 months following transplantation via quantitative in situ hybridization with 35S-radiolabeled antisense RNAs. Expression of GAD67 mRNA in the thalamic reticular nucleus was analyzed in parallel in rat pups between 0 and 30 days postnatally, and in adult animals. As already observed with immunohistochemistry, transplanted neurons of the thalamic reticular nucleus did not group in specific clusters but rather mingled with unlabeled (putatively ventrobasal) neurons. Levels of labelling for GAD67 mRNA per neuron increased over time and reached adult levels during the third week post-grafting, i.e. 2 weeks after the theoretical birthdate of the neurons (grafted at embryonic days 15-16). Similar values were observed and a plateau was reached at similar time points during normal ontogeny. The results suggest that, in contrast to morphology and size of the neuronal cell bodies, gene expression of GAD67 develops normally despite the ectopic location of neurons of the thalamic reticular nucleus in the somatosensory thalamus, the abnormal connectivity and the lack of segregation from non-GABAergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Transplante de Tecido Encefálico , Transplante de Tecido Fetal , Glutamato Descarboxilase/biossíntese , Proteínas do Tecido Nervoso/biossíntese , Neurônios/transplante , Núcleos Talâmicos/enzimologia , Tálamo/transplante , Transplante Heterotópico , Animais , Transplante de Tecido Encefálico/patologia , Indução Enzimática , Glutamato Descarboxilase/genética , Proteínas do Tecido Nervoso/genética , Neurônios/enzimologia , Ratos , Ratos Sprague-Dawley , Núcleos Talâmicos/citologia , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/crescimento & desenvolvimento , Ácido gama-Aminobutírico/biossínteseRESUMO
Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to examine the time of origin, settling pattern, migratory route, and site of origin of neurons of the ventral nuclear complex of the thalamus. Quantitative examination of long-survival radiograms established that the bulk of the neurons of the ventral nuclear complex are generated between days E14 and E16 but with statistically significant differences between its three nuclei. The ventrobasal nucleus is the oldest component (97% of the cells are generated on days E14 and E15); the ventrolateral nucleus is next (82% of the cells are generated on days E14 and E15); and the ventromedial nucleus is last (51% of the cells are generated on days E14 and E15). In addition to this caudal-to-rostral (from the ventrobasal nucleus to the ventrolateral nucleus) and lateral-to-medial (from the ventrobasal nucleus to the ventromedial nucleus) internuclear gradients, there are lateral-to-medial and ventral-to-dorsal intranuclear neurogenetic gradients within the ventrobasal and ventrolateral nuclei. Qualitative examination of short and sequential survival thymidine radiograms indicate that the neurons of the ventral nuclear complex originate in the unique intermediate thalamic neuroepithelial lobule, which is distinguished from the rest of the thalamic neuroepithelium by the presence of a mitotically active secondary neuroepithelial matrix. Two sublobules can be distinguished in the intermediate lobule during the early stages of thalamic development. On the basis of their location and chronological pattern of cell production and differentiation, it is inferred that the neurons of the ventrobasal nucleus originate in the earlier differentiating, posteroventrally situated inverted sublobule, and the neurons of the ventrolateral nucleus are produced in the later differentiating, anterodorsally situated everted sublobule. The neurons of the ventromedial nucleus appear to originate from the intermediate neuroepithelial lobule after its two sublobules are no longer distinguishable. The heavily labeled neurons generated soon after injection on day E15 form a wave front that translocates in a lateral direction at a steady rate of 215 microns/day. Examination of methacrylate-embedded materials showed that, in day E15 rats the actively migrating cells are spindle-shaped, with their long axis oriented horizontally. The far-laterally situated differentiating cells (the oldest neurons) become vertically oriented by day E16. Associated with this change in polarity, vertically oriented fibers appear among the cells. These fibers can be traced to the inte
Assuntos
Desenvolvimento Embrionário e Fetal , Núcleos Talâmicos/embriologia , Tálamo/embriologia , Animais , Diferenciação Celular , Movimento Celular , Ratos , Núcleos Talâmicos/citologia , Tálamo/citologia , TimidinaRESUMO
Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses and young pups were analyzed in order to delineate the boundaries of the proliferative thalamic neuroepithelium, describe its early transformations, identify its regional divisions, and, finally, attempt to relate its distinct neuroepithelial components to specific thalamic nuclei that they supply with neurons. On day E13 the thalamic neuroepithelium consists of two divisions, the rostral lobe and the caudal lobe, and interposed between the two is a small transient structure, the reticular protuberance. By day E14 the rostral lobe has become partitioned into the anterior lobule and the reticular lobule, and the caudal lobe into the intermediate lobule and the posterior lobule. By day E15 these four lobules have become further partitioned into sublobules, characterized as regional eversions and inversions (concavities and convexities) of the thalamic neuroepithelium. Several of these sublobules are still recognizable on day E16 but progressively disappear thereafter. In this introductory paper, some evidence is presented in support of the hypothesis that the identified thalamic sublobules represent putative cell lines committed to produce neurons for specific, early-generated thalamic nuclei. Detailed documentation of the evidence on which the identifications are based is provided in subsequent papers of this series which deal with the early development of specific thalamic regions and nuclei. In our attempt to identify these putative cell lines, we sought to meet the following criteria: (1) a good match between the time course of mitotic activity in a neuroepithelial sublobule and the birth days of neurons in the nucleus that it is postulated to supply with neurons, (2) relative proximity between the putative neuroepithelial source and the thalamic target structure, and, where possible, (3) the tracing of migrating cells from the germinal source to its destination. Using these criteria we have made the following tentative identifications. The early derivatives of the anterior thalamic lobules are the sublobules (committed cell lines) of the anterior thalamic nuclei, and of the central lateral and mediodorsal nuclei. The early derivatives of the reticular lobule and reticular protuberance are the sublobules of the reticular nuclear complex. The early derivatives of the intermediate lobule are the sublobules of the ventrolateral and ventrobasal nuclei. Finally, the early derivatives of the posterior lobule are the sublobules of the dorsal geniculate, ventral geniculate, and medial geniculate nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Desenvolvimento Embrionário e Fetal , Tálamo/embriologia , Animais , Autorradiografia , Contagem de Células , Diferenciação Celular , Ratos , Ratos Endogâmicos , Núcleos Talâmicos/citologia , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/crescimento & desenvolvimento , Tálamo/citologia , Tálamo/crescimento & desenvolvimento , TimidinaRESUMO
Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to examine the time of origin, settling pattern, and neuroepithelial site of origin of the anterior thalamic nuclei--the lateral dorsal (lateral anterior), anterodorsal, anteroventral and anteromedial nuclei--and of two rostral midline structures--the anterior paraventricular and paratenial nuclei. The neurons of the lateral dorsal nucleus are generated over a 3-day period between days E14-E16 and their settling pattern displays a combined lateral-to-medial and dorsal-to-ventral neurogenetic gradient. The bulk of the neurons of the anteroventral nucleus are generated over a 3-day period between days E15-E17 and settle with an oblique lateral-to-medial and ventral-to-dorsal neurogenetic gradient. The bulk of the neurons of the anteromedial nucleus are generated over a 2-day period between days E16-E17 and show the same settling pattern as the anteroventral nucleus. The neurons of the anterodorsal nucleus are generated over a 3-day period between days E15-E17 and show a lateral-to-medial neurogenetic gradient. The bulk of the neurons of the central part and lateral part of the paraventricular nucleus are generated over a 2-day period (E16-E17 and E17-E18, respectively) and each part displays a ventral-to-dorsal neurogenetic gradient. Finally, the bulk of the neurons of the paratenial nucleus are generated over a 4-day period between days E15-E18 and settle with a lateral-to-medial neurogenetic gradient. Observations are presented that the anterior thalamic nuclei, constituting the distinct "limbic thalamus," derive from a discrete neuroepithelial source. This is the crescent-shaped germinal matrix lining the diencephalic (medial) wall of the hitherto unrecognized anterior transitional promontory, which we call the anterior thalamic neuroepithelial lobule. On day E16 three migratory streams leave the anterior neuroepithelial lobule and, on the basis of their labeling pattern in relation to the neurogenetic gradients of the anterior thalamic nuclei, they are identified, from dorsal to ventral, as the putative migratory streams of the anterodorsal, anteroventral, and lateral dorsal nuclei. On day E17 the putative migratory stream of the anteromedial nucleus appears to leave the same neuroepithelial region that on the previous days was the source of the anteroventral nucleus. Dorsally, two neuroepithelial patches persist after day E17 and these are identified as the putative cell lines of the anterior paraventricular and paratenial nuclei.
Assuntos
Desenvolvimento Embrionário e Fetal , Tálamo/embriologia , Animais , Autorradiografia , Diferenciação Celular , Ratos , Ratos Endogâmicos , Núcleos Talâmicos/citologia , Núcleos Talâmicos/embriologia , Tálamo/citologia , TimidinaRESUMO
Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational days 13 and 14 (E13 + 14) until the day before birth (E21 + 22). With this progressively delayed comprehensive labelling procedure we determined the time of origin of neurons in the nuclei of the epithalamus, thalamus, and ventral thalamus. The zona incerta, subthalamic nucleus, reticular nucleus, posterior nucleus, and ventral lateral geniculate nucleus are composed of the earliest arising neurons (E13, or before, to E15). The neurons of the lateral habenular nucleus are produced between days E13--16. The neurons of the medial geniculate and lateral geniculate nuclei, the ventrobasal and ventrolateral complexes, and the nucleus lateralis, pars posterior, arise rapidly on days E14--15; the medial geniculate nucleus with a peak on day E14, the others with a peak on day E15. Neurons of a group of nuclei, with ill-defined boundaries medial to the sensory relax nuclei, arise apparently on days E15--16, with a peak on day E15; these may represent the intralaminar nuclei. The next group is generated on days E15--16 but with peak formation time on day E16; this includes the anteroventral, anterodorsal, anteromedial and mediodorsal nuclei. The rhomboid, reuniens and paratenial nuclei, and the paraventricular nucleus, pars anterior, arise next (E16--17). The medial habenular nucleus forms last and over a protracted period (E15--19). With their lengthy generation time the lateral and medial habenular nuclei resemble more the nuclei of the hypothalamus than the nuclei of the dorsal thalamus.