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Oscar Marín

Publications and source records attributed to Oscar Marín.

17 recordsLinked to original sources
PubMed2006

Neurons in motion: same principles for different shapes?

The special conformation of the developing nervous system, in which progenitor zones are largely confined to the lumen of the neural tube, places neuronal migration as one of the most fundamental processes in brain development. Previous studies have shown that different neuronal types adopt distinct morphological modes of migration in the developing brain, indicating that neuronal migration might be a diverse process. Here, we review recent data on the molecular mechanisms underlying neuronal migration that suggest that similar signaling principles are responsible for the frequently variable morphology of different types of migrating neuron. According to this idea, the same basic molecular mechanisms found in other cell types, such as fibroblasts, might have been adapted to the special morphological needs of migrating neurons in different regions of the developing brain.

Animals↗
PubMed2006

Abnormal laminar position and dendrite development of interneurons in the reeler forebrain.

The majority of cortical and hippocampal interneurons originate in the subcortical telencephalon and migrate tangentially into pallial regions before settling in various cortical layers. The molecular cues that regulate final positioning of specific interneurons in cortical structures have not yet been identified. The positioning of radially migrating principal neurons of the cortex and hippocampus depends upon Reelin, an extracellular protein expressed near the pial surface during embryonic development that is absent in reeler mutant mice. To determine whether the layer specification of interneurons, like that of principal neurons, requires Reelin, we crossed reeler with transgenic mice that contain Green Fluorescent Protein (GFP)-expressing Inhibitory Neurons (GINs). These neurons express basal forebrain markers Dlx1/2 in normal and reeler mice. In normal mice, GINs express Reelin and are localized to specific layers of the cortex and hippocampus. In reeler mutant mice, we show that GINs migrate normally into the pallium, but fail to acquire proper layer position. Double labeling experiments indicate that the neurochemical profile of these interneurons is not generally altered in reeler mice. However, the extension of their cellular processes is abnormal. Quantitative analysis of GINs in the cortex revealed that they are hypertrophic, bearing longer neuritic branches than normal. Thus, the lack of Reelin signaling results in abnormal positioning and altered morphology of forebrain interneurons.

Animals↗
PubMed2006

Meninges control tangential migration of hem-derived Cajal-Retzius cells via CXCL12/CXCR4 signaling.

Cajal-Retzius cells are critical in the development of the cerebral cortex, but little is known about the mechanisms controlling their development. Three focal sources of Cajal-Retzius cells have been identified in mice-the cortical hem, the ventral pallium and the septum-from where they migrate tangentially to populate the cortical surface. Using a variety of tissue culture assays and in vivo manipulations, we demonstrate that the tangential migration of cortical hem-derived Cajal-Retzius cells is controlled by the meninges. We show that the meningeal membranes are a necessary and sufficient substrate for the tangential migration of Cajal-Retzius cells. We also show that the chemokine CXCL12 secreted by the meninges enhances the dispersion of Cajal-Retzius cells along the cortical surface, while retaining them within the marginal zone in a CXCR4-dependent manner. Thus, the meningeal membranes are fundamental in the development of Cajal-Retzius cells and, hence, in the normal development of the cerebral cortex.

Animals↗
PubMed2006

Layer acquisition by cortical GABAergic interneurons is independent of Reelin signaling.

Functioning of the cerebral cortex requires the coordinated assembly of circuits involving glutamatergic projection neurons and GABAergic interneurons. Despite their segregated origin in different regions of the telencephalon, projection neurons and interneurons born synchronically end up adopting the same cortical layer, suggesting that layer acquisition is highly coordinated for both neuronal types. The radial migration and laminar arrangement of projection neurons depends on Reelin, a secreted glycoprotein expressed near the pial surface during embryogenesis. In contrast, the mechanisms controlling layer acquisition by cortical interneurons remain essentially unknown. Here, we have used an ultrasound-guided transplantation approach to analyze the mechanisms underlying the acquisition of laminar locations by cortical interneurons. We found that layer acquisition by cortical GABAergic interneurons does not directly depend on Reelin signaling. Moreover, interneurons invade their target layers well after synchronically generated projection neurons reach their final destination. These results suggest a model in which cues provided by projection neurons guide cortical interneurons to their appropriate layer, and reveal that, at least for some neuronal types, long-range radial migration does not directly require Reelin.

Animals↗
PubMed2006

Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation.

Neuronal migration and axon guidance constitute fundamental processes in brain development that are generally studied independently. Although both share common mechanisms of cell biology and biochemistry, little is known about their coordinated integration in the formation of neural circuits. Here we show that the development of the thalamocortical projection, one of the most prominent tracts in the mammalian brain, depends on the early tangential migration of a population of neurons derived from the ventral telencephalon. This tangential migration contributes to the establishment of a permissive corridor that is essential for thalamocortical axon pathfinding. Our results also demonstrate that in this process two different products of the Neuregulin-1 gene, CRD-NRG1 and Ig-NRG1, mediate the guidance of thalamocortical axons. These results show that neuronal tangential migration constitutes a novel mechanism to control the timely arrangement of guidance cues required for axonal tract formation in the mammalian brain.

Animals↗
PubMed2005

Developmental mechanisms underlying the generation of cortical interneuron diversity.

GABAergic interneurons are critical components of cortical circuits. However, understanding their function has become extremely challenging because they constitute one of the most diverse groups of cells in the central nervous system. Indeed, cortical GABAergic interneurons are heterogeneous in so many different ways--morphology, molecular profiling, electrical properties--that even attempts to discern what parameters should be used to identify cortical interneuron subtypes have failed to generate broad consensus among experts in the field. The extent to which cortical interneuron diversity emerges during development is largely unknown, but it is likely that insights on how this process takes place may help us understand their role as integrative and synchronizing elements in cortical function. Here, we review recent data on how the large variety of distinct classes of cortical interneurons may arise during development.

Animals↗
PubMed2004

Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1.

Most cortical interneurons arise from the subcortical telencephalon, but the molecules that control their migration remain largely unidentified. Here, we show that different isoforms of Neuregulin-1 are expressed in the developing cortex and in the route that migrating interneurons follow toward the cortex, whereas a population of the migrating interneurons express ErbB4, a receptor for Neuregulin-1. The different isoforms of Neuregulin-1 act as short- and long-range attractants for migrating interneurons, and perturbing ErbB4 function in vitro decreases the number of interneurons that tangentially migrate to the cortex. In vivo, loss of Neuregulin-1/ErbB4 signaling causes an alteration in the tangential migration of cortical interneurons and a reduction in the number of GABAergic interneurons in the postnatal cortex. These observations provide evidence that Neuregulin-1 and its ErbB4 receptor directly control neuronal migration in the nervous system.

Animals↗
PubMed2003

The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain.

Forebrain cholinergic neurons play important roles as striatal local circuit neurons and basal telencephalic projection neurons. The genetic mechanisms that control development of these neurons suggest that most of them are derived from the basal telencephalon where Lhx8, a LIM-homeobox gene, is expressed. Here we report that mice with a null mutation of Lhx8 are deficient in the development of forebrain cholinergic neurons. Lhx8 mutants lack the nucleus basalis, a major source of the cholinergic input to the cerebral cortex. In addition, the number of cholinergic neurons is reduced in several other areas of the subcortical forebrain in Lhx8 mutants, including the caudate-putamen, medial septal nucleus, nucleus of the diagonal band, and magnocellular preoptic nucleus. Although cholinergic neurons are not formed, initial steps in their specification appear to be preserved, as indicated by a presence of cells expressing a truncated Lhx8 mRNA and mRNA of the homeobox gene Gbx1. These results provide genetic evidence supporting an important role for Lhx8 in development of cholinergic neurons in the forebrain.

Animals↗
PubMed2003

Cell migration in the forebrain.

The forebrain comprises an intricate set of structures that are required for some of the most complex and evolved functions of the mammalian brain. As a reflection of its complexity, cell migration in the forebrain is extremely elaborated, with widespread dispersion of cells across multiple functionally distinct areas. Two general modes of migration are distinguished in the forebrain: radial migration, which establishes the general cytoarchitectonical framework of the different forebrain subdivisions; and tangential migration, which increases the cellular complexity of forebrain circuits by allowing the dispersion of multiple neuronal types. Here, we review the cellular and molecular mechanisms underlying each of these types of migrations and discuss how emerging concepts in neuronal migration are reshaping our understanding of forebrain development in normal and pathological situations.

Animals↗
PubMed2003

Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons.

The ventromedial hypothalamic nucleus (VMN) is known to mediate autonomic responses in feeding and reproductive behaviors. To date, the most definitive molecular marker for the VMN is the orphan nuclear receptor steroidogenic factor-1 (SF-1). However, it is unclear whether SF-1 functions in the VMN as it does in peripheral endocrine organ development where loss of SF-1 results in organ agenesis due to apoptosis. Here, we provide evidence that SF-1 has a distinct role in later stages of VMN development by demonstrating the persistence of VMN precursors, the misexpression of an early marker (NKX2-1) concomitant with the absence of a late marker (BDNF neurotrophin), and the complete loss of projections to the bed nucleus of stria terminalis and the amygdala in sf-1 null mice. Our findings demonstrate that SF-1 is required for terminal differentiation of the VMN and suggest that transcriptional targets of SF-1 mediate normal circuitry between the hypothalamus and limbic structures in the telencephalon.

Amygdala↗
PubMed2003

Directional guidance of interneuron migration to the cerebral cortex relies on subcortical Slit1/2-independent repulsion and cortical attraction.

Tangential migration from the basal telencephalon to the cortex is a highly directional process, yet the mechanisms involved are poorly understood. Here we show that the basal telencephalon contains a repulsive activity for tangentially migrating cells, whereas the cerebral cortex contains an attractive activity. In vitro experiments demonstrate that the repulsive activity found in the basal telencephalon is maintained in mice deficient in both Slit1 and Slit2, suggesting that factors other than these are responsible for this activity. Correspondingly, in vivo analysis demonstrates that interneurons migrate to the cortex in the absence of Slit1 and Slit2, or even in mice simultaneously lacking Slit1, Slit2 and netrin 1. Nevertheless, loss of Slit2 and, even more so, Slit1 and Slit2 results in defects in the position of other specific neuronal populations within the basal telencephalon, such as the cholinergic neurons of the basal magnocellular complex. These results demonstrate that whereas Slit1 and Slit2 are not necessary for tangential migration of interneurons to the cortex, these proteins regulate neuronal migration within the basal telencephalon by controlling cell positioning close to the midline.

Animals↗
PubMed2002

Localization of choline acetyltransferase (ChAT) immunoreactivity in the brain of a caecilian amphibian, Dermophis mexicanus (Amphibia: Gymnophiona).

The organization of the cholinergic system in the brain of anuran and urodele amphibians was recently studied, and significant differences were noted between both amphibian orders. However, comparable data are not available for the third order of amphibians, the limbless gymnophionans (caecilians). To further assess general and derived features of the cholinergic system in amphibians, we have investigated the distribution of choline acetyltransferase immunoreactive (ChAT-ir) cell bodies and fibers in the brain of the gymnophionan Dermophis mexicanus. This distribution showed particular features of gymnophionans such as the existence of a particularly large cholinergic population in the striatum, the presence of ChAT-ir cells in the mesencephalic tectum, and the organization of the cranial nerve motor nuclei. These peculiarities probably reflect major adaptations of gymnophionans to a fossorial habit. Comparison of our results with those in other vertebrates, including a segmental approach to correlate cell populations across species, shows that the general pattern of organization of cholinergic systems in vertebrates can be modified in certain species in response to adaptative processes that lead to morphological and behavioral modifications of members of a given class of vertebrates, as shown for gymnophionans.

Acetylcholine↗
PubMed2002

Slit proteins prevent midline crossing and determine the dorsoventral position of major axonal pathways in the mammalian forebrain.

We report that Slit proteins, a family of secreted chemorepellents, are crucial for the proper development of several major forebrain tracts. Mice deficient in Slit2 and, even more so, mice deficient in both Slit1 and Slit2 show significant axon guidance errors in a variety of pathways, including corticofugal, callosal, and thalamocortical tracts. Analysis of multiple pathways suggests several generalizations regarding the functions of Slit proteins in the brain, which appear to contribute to (1) the maintenance of dorsal position by prevention of axonal growth into ventral regions, (2) the prevention of axonal extension toward and across the midline, and (3) the channeling of axons toward particular regions.

Afferent Pathways↗
PubMed2002

Patterning of the basal telencephalon and hypothalamus is essential for guidance of cortical projections.

We have investigated the mechanisms that control the guidance of corticofugal projections as they extend along different subdivisions of the forebrain. To this aim, we analyzed the development of cortical projections in mice that lack Nkx2-1, a homeobox gene whose expression is restricted to two domains within the forebrain: the basal telencephalon and the hypothalamus. Molecular respecification of the basal telencephalon and hypothalamus in Nkx2-1-deficient mice causes a severe defect in the guidance of layer 5 cortical projections and ascending fibers of the cerebral peduncle. These axon tracts take an abnormal path when coursing through both the basal telencephalon and hypothalamus. By contrast, loss of Nkx2-1 function does not impair guidance of corticothalamic or thalamocortical axons. In vitro experiments demonstrate that the basal telencephalon and the hypothalamus contain an activity that repels the growth of cortical axons, suggesting that loss of this activity is the cause of the defects observed in Nkx2-1 mutants. Furthermore, analysis of the expression of candidate molecules in the basal telencephalon and hypothalamus of Nkx2-1 mutants suggests that Slit2 contributes to this activity.

Animals↗
PubMedDate not supplied

Organization of cholinergic systems in the brain of different fish groups: a comparative analysis.

Using choline acetyltransferase immunocytochemistry, we compared the cholinergic systems of the brains of four groups of fishes (lampreys, elasmobranchs, chondrosteans, and teleosts). Cholinergic nuclei were classified in four groups according to their distribution in vertebrates. The cranial motor nuclei and the habenulo-interpeduncular system were cholinergic in all vertebrates. The cholinergic nuclei of the isthmus of fishes showed many similarities with those of tetrapods. The magnocellular preoptic neurosecretory cells were cholinergic in most fishes, whereas in neurosecretory nuclei of tetrapods, cholinergic cells were only observed adjacent to the magnocellular cells. In the subpallium, cholinergic cells were observed in all fishes, with the exception of elasmobranchs, which suggests that they might be secondarily lost. In the pallium of fishes, cholinergic neurons were only observed in elasmobranchs. Because pallial cholinergic cells were only observed in lizard and mammals, they could have appeared several times during evolution. The same is suggested for the presence of cholinergic cells in the optic tectum of only a few vertebrate groups, including teleosts. This preliminary analysis enlarges our knowledge of the cholinergic systems of fishes, although more species and groups need to be studied to provide a more complete scenario of their evolution.

Acetylcholinesterase↗
PubMedDate not supplied

Distribution and origin of the catecholaminergic innervation in the amphibian mesencephalic tectum.

The mesencephalic tectum plays a prominent role in integrating both visual and multimodal sensory information essential for normal behavior in amphibians. Activity in the mesencephalic tectum is thought to be modulated by the influence of distinct neurochemical inputs, including the catecholaminergic and the cholinergic systems. In the present study, we have investigated the distribution and the origin of the catecholaminergic innervation of the mesencephalic tectum in two amphibian species, the anuran Rana perezi and the urodele Pleurodeles waltl. Immunohistochemistry for dopamine and two enzymes required for the synthesis of catecholamines, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), revealed a complex pattern of catecholaminergic (CA) innervation in the anuran and urodele mesencephalic tectum. Dopaminergic fibers were primarily present in deep tectal layers, whereas noradrenergic (DBH immunoreactive) fibers predominated in superficial layers. Catecholaminergic cell bodies were never observed within the tectum. To determine the origin of this innervation, applications of retrograde tracers into the optic tectum were combined with immunohistochemistry for TH. Results from these experiments demonstrate that dopaminergic neurons in the suprachiasmatic and juxtacommissural nuclei (in Rana) or in the nucleus pretectalis (in Pleurodeles), together with noradrenergic cells of the locus coeruleus, are the sources of CA input to the amphibian mesencephalic tectum. The present results suggest that similar CA modulatory inputs are present in the mesecencephalic tectum of both anurans and urodeles.

Afferent Pathways↗