San Juan de Moró, Spain
San Juan de Moró, Spain

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Pombero A.,Institute Neurociencias UMH CSIC | Bueno C.,Institute Neurociencias UMH CSIC | Saglietti L.,CNR Institute of Neuroscience | Rodenas M.,Institute Neurociencias UMH CSIC | And 3 more authors.
Development | Year: 2011

The majority of the cortical cholinergic innervation implicated in attention and memory originates in the nucleus basalis of Meynert and in the horizontal limb of the diagonal band nucleus of the basal prosencephalon. Functional alterations in this system give rise to neuropsychiatric disorders as well as to the cognitive alterations described in Parkinson and Alzheimer's diseases. Despite the functional importance of these basal forebrain cholinergic neurons very little is known about their origin and development. Previous studies suggest that they originate in the medial ganglionic eminence of the telencephalic subpallium; however, our results identified Tbr1-expressing, reelin-positive neurons migrating from the ventral pallium to the subpallium that differentiate into cholinergic neurons in the basal forebrain nuclei projecting to the cortex. Experiments with Tbr1 knockout mice, which lack ventropallial structures, confirmed the pallial origin of cholinergic neurons in Meynert and horizontal diagonal band nuclei. Also, we demonstrate that Fgf8 signaling in the telencephalic midline attracts these neurons from the pallium to follow a tangential migratory route towards the basal forebrain. © 2011. Published by The Company of Biologists Ltd.


PubMed | University of California at San Francisco, Allen Institute for Brain Science, University of Murcia, Instituto Of Neurociencias Umh Csic and Institute Neurociencias UMH CSIC
Type: Journal Article | Journal: Neuron | Year: 2014

To provide a temporal framework for the genoarchitecture of brain development, we generated in situ hybridization data for embryonic and postnatal mouse brain at seven developmental stages for 2,100 genes, which were processed with an automated informatics pipeline and manually annotated. This resource comprises 434,946 images, seven reference atlases, an ontogenetic ontology, and tools to explore coexpression of genes across neurodevelopment. Gene sets coinciding with developmental phenomena were identified. A temporal shift in the principles governing the molecular organization of the brain was detected, with transient neuromeric, plate-based organization of the brain present at E11.5 and E13.5. Finally, these data provided a transcription factor code that discriminates brain structures and identifies the developmental age of a tissue, providing a foundation for eventual genetic manipulation or tracking of specific brain structures over development. The resource is available as the Allen Developing Mouse Brain Atlas (http://developingmouse.brain-map.org).


Navarro-Garberi M.,Institute Neurociencias UMH CSIC | Bueno C.,University of Murcia | Martinez S.,Institute Neurociencias UMH CSIC | Martinez S.,University of Murcia
Brain Structure and Function | Year: 2015

The diencephalon is a complex brain area that derives from the caudal region of the prosencephalon. This structure is divided into four longitudinal neuroepithelial zones: roof, alar, basal and floor plates, which constitute its dorso-ventral (DV) columnar domains. Morphogenetic differences between alar and basal plates in the prosencephalon and mesencephalon contribute to the characteristic expansion of alar plate derivatives in the brain and the formation of the cephalic flexure. Although differential histogenesis among DV regions seems to be relevant in understanding structural and functional complexity of the brain, most of our knowledge about DV regionalization comes from the spinal cord development. Therefore, it seems of interest to study the molecular mechanisms that govern DV patterning in the diencephalon, the brain region where strong differences in size and complexity between alar and basal derivatives are evident in all vertebrates. Different morphogenetic signals, which induce specific progenitors fate to the neighboring epithelium, are involved in the spinal cord DV patterning. To study if Wnt1, one of these signaling molecules, has a role for the establishment of the diencephalic longitudinal domains, we carried out gain- and loss-of-function experiments, using mice and chick embryos. Our results demonstrated functional differences in the molecular mechanisms downstream of Wnt1 function in the diencephalon, in relation to the spinal cord. We further demonstrated that Bmp4 signal induces Wnt1 expression in the diencephalon, unraveling a new molecular regulatory code downstream of primary dorsalizing signals to control ventral regionalization in the diencephalon. © 2015 Springer-Verlag Berlin Heidelberg


PubMed | University of Murcia and Institute Neurociencias UMH CSIC
Type: Journal Article | Journal: Brain structure & function | Year: 2016

The diencephalon is a complex brain area that derives from the caudal region of the prosencephalon. This structure is divided into four longitudinal neuroepithelial zones: roof, alar, basal and floor plates, which constitute its dorso-ventral (DV) columnar domains. Morphogenetic differences between alar and basal plates in the prosencephalon and mesencephalon contribute to the characteristic expansion of alar plate derivatives in the brain and the formation of the cephalic flexure. Although differential histogenesis among DV regions seems to be relevant in understanding structural and functional complexity of the brain, most of our knowledge about DV regionalization comes from the spinal cord development. Therefore, it seems of interest to study the molecular mechanisms that govern DV patterning in the diencephalon, the brain region where strong differences in size and complexity between alar and basal derivatives are evident in all vertebrates. Different morphogenetic signals, which induce specific progenitors fate to the neighboring epithelium, are involved in the spinal cord DV patterning. To study if Wnt1, one of these signaling molecules, has a role for the establishment of the diencephalic longitudinal domains, we carried out gain- and loss-of-function experiments, using mice and chick embryos. Our results demonstrated functional differences in the molecular mechanisms downstream of Wnt1 function in the diencephalon, in relation to the spinal cord. We further demonstrated that Bmp4 signal induces Wnt1 expression in the diencephalon, unraveling a new molecular regulatory code downstream of primary dorsalizing signals to control ventral regionalization in the diencephalon.


Garcia-Calero E.,Institute Neurociencias UMH CSIC | Botella-Lopez A.,Institute Neurociencias UMH CSIC | Bahamonde O.,Institute Neurociencias UMH CSIC | Bahamonde O.,Fundacion Investigacion Clinico Of Valencia Institute Investigacion Sanitaria Incliva | And 3 more authors.
Brain Structure and Function | Year: 2016

In the mammalian telencephalon, part of the progenitor cells transition from multipolar to bipolar morphology as they invade the mantle zone. This associates with changing patterns of radial migration. However, the molecules implicated in these morphology transitions are not well known. In the present work, we analyzed the function of FoxP2 protein in this process during telencephalic development in vertebrates. We analyzed the expression of FoxP2 protein and its relation with cell morphology and migratory patterns in mouse and chicken developing striatum. We observed FoxP2 protein expressed in a gradient from the subventricular zone to the mantle layer in mice embryos. In the FoxP2 low domain cells showed multipolar migration. In the striatal mantle layer where FoxP2 protein expression is higher, cells showed locomoting migration and bipolar morphology. In contrast, FoxP2 showed a high and homogenous expression pattern in chicken striatum, thus bipolar morphology predominated. Elevation of FoxP2 in the striatal subventricular zone by in utero electroporation promoted bipolar morphology and impaired multipolar radial migration. In mouse cerebral cortex we obtained similar results. FoxP2 promotes transition from multipolar to bipolar morphology by means of gradiental expression in mouse striatum and cortex. Together these results indicate a role of FoxP2 differential expression in cell morphology control of the vertebrate telencephalon. © 2015, Springer-Verlag Berlin Heidelberg.

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