Propuesta de intervención en Educación Infantil para trabajar las ciencias experimentales a través de los cinco sentidos

Las ciencias desempeñan un papel fundamental en la educación infantil debido a su importancia para comprender el mundo que nos rodea. Es por esto que se reconoce la relevancia de involucrar a los niños y las niñas en experiencias científicas desde temprana edad, ya que esto les permite desarrollar habilidades cognitivas, explorar su entorno y construir una comprensión sólida del mundo que les rodea. En el presente trabajo se revisa la literatura existente sobre la importancia de las ciencias experimentales en la educación infantil y cómo estas pueden influir en el desarrollo integral de los niños, es por esto que se destaca la relevancia de utilizar los cinco sentidos como herramienta para la exploración y comprensión del entorno científico. La propuesta de intervención está ligada a los enfoques constructivistas y el uso de actividades basada en talleres y rincones sensoriales. Al trabajar a través de los cinco sentidos, se busca estimular la curiosidad, promover la exploración y fomentar el pensamiento científico desde una edad temprana. Es por esto que el resultado de esta propuesta basada en los talleres y rincones puede ser satisfactoria y significativa para el aprendizaje del alumnado, a su vez que también se pueden trabajar estos contenidos con otro tipo de estrategias metodológicas existentes.<br /

Inhibitory synapse dysfunction and epileptic susceptibility associated with KIF2A deletion in cortical interneurons

Malformation of cortical development (MCD) is a family of neurodevelopmental disorders, which usually manifest with intellectual disability and early-life epileptic seizures. Mutations in genes encoding microtubules (MT) and MT-associated proteins are one of the most frequent causes of MCD in humans. KIF2A is an atypical kinesin that depolymerizes MT in ATP-dependent manner and regulates MT dynamics. In humans, single de novo mutations in KIF2A are associated with MCD with epileptic seizures, posterior pachygyria, microcephaly, and partial agenesis of corpus callosum. In this study, we conditionally ablated KIF2A in forebrain inhibitory neurons and assessed its role in development and function of inhibitory cortical circuits. We report that adult mice with specific deletion of KIF2A in GABAergic interneurons display abnormal behavior and increased susceptibility to epilepsy. KIF2A is essential for tangential migration of cortical interneurons, their positioning in the cerebral cortex, and for formation of inhibitory synapses in vivo. Our results shed light on how KIF2A deregulation triggers functional alterations in neuronal circuitries and contributes to epilepsy

DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma

Background: Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors. Methods: We analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient's survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach. Results: We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient's survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region. Conclusion: We propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma

DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma

Background: Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors. Methods: We analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient's survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach. Results: We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient's survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region. Conclusion: We propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma

Lateral thalamic eminence – a novel origin for mGluR1/lot cells

A unique population of cells, called "lot cells," circumscribes the path of the lateral olfactory tract (LOT) in the rodent brain and acts to restrict its position at the lateral margin of the telencephalon. Lot cells were believed to originate in the dorsal pallium (DP). We show that Lhx2 null mice that lack a DP show a significant increase in the number of mGluR1/lot cells in the piriform cortex, indicating a non-DP origin of these cells. Since lot cells present common developmental features with Cajal-Retzius (CR) cells, we analyzed Wnt3a- and Dbx1-reporter mouse lines and found that mGluR1/lot cells are not generated in the cortical hem, ventral pallium, or septum, the best characterized sources of CR cells. Finally, we identified a novel origin for the lot cells by combining in utero electroporation assays and histochemical characterization. We show that mGluR1/lot cells are specifically generated in the lateral thalamic eminence and that they express mitral cell markers, although a minority of them express DeltaNp73 instead. We conclude that most mGluR1/lot cells are prospective mitral cells migrating to the accessory olfactory bulb (OB), whereas mGluR1+, DeltaNp73+ cells are CR cells that migrate through the LOT to the piriform cortex and the OB

DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma

BackgroundGlioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors.MethodsWe analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient’s survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach.ResultsWe found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient’s survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region.ConclusionWe propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma

The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala

In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medial ganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novel model of the neuronal composition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.This work was supported by Grants of the French National Research Agency (Agence Nationale de la Recherche; ANR) [ANR-13-BSV4-0011] and by the French Government through the ‘Investments for the Future’ LABEX SIGNALIFE [ANR-11-LABX-0028-01] to M.S., by the Spanish Government (BFU2007-60263 and BFU2010-17305) to A.F, and by the Medical Research Council (MR/K013750/1) to T.T. N.R.-R. is funded by a postdoctoral fellowship from the Ville de Nice, France (“Aide Individuelle aux Jeunes Chercheurs 2016”).Peer reviewe

Characterization and fate mapping of the thalamic eminence and the caudoventral pallium in mice

Durante el desarrollo embrionario, los organizadores cerebrales secretan moléculas, señales necesarias para el correcto modelaje de las diferentes subdivisiones del sistema nervioso. En el caso del telencéfalo, los organizadores secretan morfógenos tales como proteínas morfogenéticas del hueso (bone morphogenetic proteins; BMP), factores de crecimiento de fibroblastos (fibroblast growth factors; FGF) y proteínas Wnt. En particular, el factor de diferenciación de crecimiento Gdf10 (Bmp-3b) es un morfógeno expresado en dos regiones discretas del prosencéfalo, la eminencia talámica (ET) y el palio caudoventral. La ET y el palio caudoventral comparten la expresión de muchos otros morfógenos a parte de Gdf10 y ambos territorios generan neuronas glutamatérgicas. Estas dos regiones se localizan en la parte más caudal del palio, formando el límite entre diencéfalo y telencéfalo. Estas propiedades le hacen ser centros de señalización putativos para el prosencéfalo. En esta tesis, realizamos una caracterización genética y anatómica de la ET y del palio caudoventral, introducimos un nuevo modelo del límite diencefálico telencefálico y describimos por primera vez las poblaciones neuronales generadas por la ET y el palio caudoventral. Esta tesis ha sido dividida en dos secciones: SECTION 1: La eminencia talámica lateral es el origen principal de las células lot La eminencia talámica (ET) es una estructura transitoria localizada en el prosómero diencefálico 3. Aquí mostramos que la ET está integrada en dos subregiones, la ET lateral y la medial. La ET lateral, se localiza seguida del hem cortical, forma un continuo con esta estructura y es genéticamente relacionada con el telencéfalo. En esta tesis demostraremos que la ET lateral es una fuente de células mGluR1 positivas (también llamadas células lot) que migran a través del territorio del tracto olfativo lateral antes de la llegada de los axones de las células mitrales. Nuestros resultados también revelan que las células mGluR1/lot no son una única población. En su lugar se trata de una mezcla de al menos dos conjuntos de neuronas diferentes. (i) Las precursoras de las células mitrales que poblarán el bulbo olfativo accesorio posterior y, (ii) una pequeña población de células de Cajal-Retzius positivas para mGluR1+ y p73+ que se localizan alrededor de los axones del tracto olfativo lateral y esparcidas por la corteza piriforme.SECTION 2: El palio caudoventral como origen putativo de neuronas glutamatergicas amigdalinas. The palio caudoventral es un territorio palial situado en la parte más caudal del palio ventral y que se continua anatómicamente con la eminencia talámica. Al igual que el palio ventral, el territorio del palio caudoventral expresa marcadores tales como Gdf10, Sfrp2 y Fgf15, pero es negativo para Dbx1, un factor de transcripción implicado en neurogénesis glutamatérgica en el palio ventral. El palio caudoventral genera células glutamatérgicas que expresan Ebf3 durante estadios embrionarios y que poblarán el revestimiento del núcleo medial de la amígdala

Rostro-Caudal and Caudo-Rostral Migrations in the Telencephalon: Going Forward or Backward?

The generation and differentiation of an appropriate number of neurons, as well as its distribution in different parts of the brain, is crucial for the proper establishment, maintenance and plasticity of neural circuitries. Newborn neurons travel along the brain in a process known as neuronal migration, to finalize their correct position in the nervous system. Defects in neuronal migration produce abnormalities in the brain that can generate neurodevelopmental pathologies, such as autism, schizophrenia and intellectual disability. In this review, we present an overview of the developmental origin of the different telencephalic subdivisions and a description of migratory pathways taken by distinct neural populations traveling long distances before reaching their target position in the brain. In addition, we discuss some of the molecules implicated in the guidance of these migratory paths and transcription factors that contribute to the correct migration and integration of these neurons