1,721,010 research outputs found
Emx1, Emx2 and Pax6 in specification, regionalization and arealization of the cerebral cortex
No full textThree basic aspects of cerebral cortex development — specification of cortical versus ganglionic identity, regionalization of the early cortical primordium and arealization of the developing cortex — were the main subject of our recent investigations. We previously demonstrated that the two homeobox genes Emx2 and Pax6 promote development of caudal–medial and rostral–lateral cortex, respect- ively, by properly shaping the early cortical protomap and possibly modulating the tangential growth ratio between medial and lateral cortical anlagen. More recently, by analyzing the brains of embryos bearing mutations for Emx2 and Pax6 in different combinations, we found that both genes are necessary and sufficient for a more basic developmental choice, i.e. the specification of neuroblasts in the dorsal telencephalon as cortical versus ganglionic neuroblasts. Finally, we explored the possible roles of the Emx2 paralog, Emx1, in these processes. By looking at embryos mutant for Emx1, Emx2 and Pax6 in various combinations, we did not get any evidence of Emx1 involvement in the process of cortical specification; conversely, this gene appeared to be involved to some extent in the process of regionalization of the cortical primordium along the medial–lateral axis, as a promoter of medial fates
Gene networks controlling early cerebral cortex arealization
No full textEarly thalamus-independent steps in the process of cortical arealization take place on the basis of information intrinsic to the cortical primordium, as proposed by Rakic in his classical protomap hypothesis [Rakic, P. (1988) Science, 241, 170–176]. These steps depend on a dense network of molecular interactions, involving genes encoding for diffusible ligands which are released around the borders of the cortical field, and transcription factor genes which are expressed in graded ways throughout this field. In recent years, several labs worldwide have put considerable effort into identifying members of this network and disentangling its topology. In this respect, a considerable amount of knowledge has accumulated and a first, provisional description of the network can be delineated. The aim of this review is to provide an organic synthesis of our current knowledge of molecular genetics of early cortical arealization, i.e. to summarise the mechanisms by which secreted ligands and graded transcription factor genes elaborate positional information and trigger the activation of distinctive area-specific morphogenetic programs
Foxg1 confines Cajal-Retzius neuronogenesis and hippocampal morphogenesis to the dorsomedial pallium
Full text linkIt has been suggested that cerebral cortex arealization relies on positional values imparted to early cortical neuroblasts by transcription factor genes expressed within the pallial field in graded ways. Foxg1, encoding for one of these factors, previously was reported to be necessary for basal ganglia morphogenesis, proper tuning of cortical neuronal differentiation rates, and the switching of cortical neuro- blasts from early generation of primordial plexiform layer to late production of cortical plate. Being expressed along a rostral/lateral high- to-caudal/medial low gradient, Foxg1, moreover, could contribute to shaping the cortical areal profile as a repressor of caudomedial fates. We tested this prediction by a variety of approaches and found that it was correct. We found that overproduction of Cajal–Retzius neurons characterizing Foxg1/ mutants does not arise specifically from blockage of laminar histogenetic progression of neocortical neuro- blasts, as reported previously, but rather reflects lateral-to-medial repatterning of their cortical primordium. Even if lacking a neocortical plate, Foxg1/ embryos give rise to structures, which, for molecular properties and birthdating profile, are highly reminiscent of hippocampal plate and dentate blade. Remarkably, in the absence of Foxg1, additional inactivation of the medial fates promoter Emx2, although not suppressing cortical specification, conversely rescues overproduction of Reelin on neurons
Assessing Neuronogenic Versus Astrogenic Bias of Neural Stem Cells Via In Vitro Clonal Assay
No full textWithin the developing cerebral cortex, neural stem cells (NSCs) give rise to neurons and glial cells, according to complex spatio-temporal trajectories. In this respect, a key issue is how NSCs are committed to different neural lineages in time and space. Clonal assays are a powerful tool to address this issue. Here we describe an easy clonal assay protocol employable to dissect NSCs lineage commitment and molecular mechanisms underlying it. NSCs of distinctive spatio-temporal origin, and/or having undergone different molecular manipulations, are plated at low density and allowed to differentiate for a few days. Then, systematic immunoprofiling of the resulting clones allows to quantify commitment of their NSC ancestors to neuronal and astroglial fates
Vertebrate homeobox genes
No full textIn the former part of the review the principal available data about Hox genes, their molecular organisation and their expression in vertebrate embryos, with particular emphasis for mammals, are briefly summarized. In the latter part we analysed the expression of four mouse homeobox genes related to two Drosophila genes expressed in the developing head of the fly: Emx1 and Emx2, related to ems, and Otx1 and Otx2, related to otd. © 1994 Kluwer Academic Publishers
Cortico-cerebral histogenesis in the opossum <it>Monodelphis domestica</it>: generation of a hexalaminar neocortex in the absence of a basal proliferative compartment
Full text linkAbstract Background The metatherian Monodelphis domestica, commonly known as the South-American short-tailed opossum, is an appealing animal model for developmental studies on cortico-cerebral development. Given its phylogenetic position, it can help in tracing evolutionary origins of key traits peculiar to the eutherian central nervous system. The capability of its pup to regenerate damaged cortico-spinal connections makes it an ideal substrate for regenerative studies. Recent sequencing of its genome and the ex utero accessibility of its developing cerebral cortex further enhance its experimental interest. However, at the moment, a comprehensive cellular and molecular characterization of its cortical development is missing. Results A systematic analysis of opossum cortico-cerebral development was performed, including: origin of cortical neurons; migration of these neurons from their birthplaces to their final layer destinations; and molecular differentiation of distinct neocortical laminae. We observed that opossum projection neurons and interneurons are generated by pallial and subpallial precursors, respectively, similar to rodents. A six-layered cortex with a eutherian-like molecular profile is laid down, according to the inside-out rule. However, neocortical projection neurons are generated by apical neural precursors and almost no basal progenitors may be found in the neuronogenic neopallial primordium. In the opossum neocortex, Tbr2, the hallmark of eutherian basal progenitors, is transiently expressed by postmitotic progenies of apical precursors prior to the activation of more mature neuronal markers. Conclusions The neocortical developmental program predates Eutheria-Methatheria branching. However, in metatherians, unlike eutherians, a basal proliferative compartment is not needed for the formation of a six-layered neuronal blueprint.</p
The pro-differentiating role of miR-124: Indicating the road to become a neuron
No full textmiRNAs are essential post-transcriptional modulators affecting cell identity and fate, with a central role in cellular and developmental processes. The brain-enriched neuronal specific miRNAs-124 has been identified as a promoter of neuronogenesis in various conditions, in vitro and in vivo, with a potential role in regulating also activities of post-mitotic neurons, such as synaptic plasticity and memory formation. In this point of view, we recapitulate the main experimental findings substantiating the positive correlation between miR- 124 expression and neuronogenesis progression. Then, we describe the impact of miR-124 on the molecular network driving the profound changes which take place in differentiating neuronal cells. Finally, we consider the possibility of a post- transcriptional modulation of miR-124 biogenesis, which may finely regulate—in turn—the activities of miR-124 in neural precursor cells
Cloning and characterisation of two chick homeobox genes, members of the six/sine oculis family, expressed during eye development
No full textIntraventricular Transplantation of Engineered Neuronal Precursors for In Vivo Neuroarchitecture Studies
Full text linkGene control of neuronal cytoarchitecture is currently the subject of intensive investigation. Described here is a simple method developed to study in vivo gene control of neocortical projection neuron morphology. This method is based on (1) in vitro lentiviral engineering of neuronal precursors as "test" and "control" cells, (2) their co-transplantation into wild-type brains, and (3) paired morphometric evaluation of their neuronal derivatives. Specifically, E12.5 pallial precursors from panneuronal, genetically labeled donors, are employed for this purpose. They are engineered to take advantage of selected promoters and tetON/OFF technology, and they are free-hand transplanted into neonatal lateral ventricles. Later, upon immunofluorescence profiling of recipient brains, silhouettes of transplanted neurons are fed into NeurphologyJ open source software, their morphometric parameters are extracted, and average length and branching index are calculated. Compared to other methods, this one offers three main advantages: it permits achieving of fine control of transgene expression at affordable costs, it only requires basic surgical skills, and it provides statistically reliable results upon analysis of a limited number of animals. Because of its design, however, it is not adequate to address non cell-autonomous control of neuroarchitecture. Moreover, it should be preferably used to investigate neurite morphology control after completion of neuronal migration. In its present formulation, this method is exquisitely tuned to investigate gene control of glutamatergic neocortical neuron architecture. Taking advantage of transgenic lines expressing EGFP in other specific neural cell types, it can be re-purposed to address gene control of their architecture
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