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intermediate cortical progenitor

Juan Pablo Fededa, Christopher Esk, Beata Mierzwa, Rugile Stanyte, Shuiqiao Yuan, Huili Zheng, Klaus Ebnet, Wei Yan, Juergen A Knoblich, Daniel W Gerlich
Correct orientation of the mitotic spindle determines the plane of cellular cleavage and is crucial for organ development. In the developing cerebral cortex, spindle orientation defects result in severe neurodevelopmental disorders, but the precise mechanisms that control this important event are not fully understood. Here, we use a combination of high-content screening and mouse genetics to identify the miR-34/449 family as key regulators of mitotic spindle orientation in the developing cerebral cortex. By screening through all cortically expressed miRNAs in HeLa cells, we show that several members of the miR-34/449 family control mitotic duration and spindle rotation...
October 5, 2016: EMBO Journal
Inseyah Bagasrawala, Fani Memi, Nevena V Radonjić, Nada Zecevic
N-methyl d-aspartate receptors (NMDARs), a subtype of glutamate receptor, have important functional roles in cellular activity and neuronal development. They are well-studied in rodent and adult human brains, but limited information is available about their distribution in the human fetal cerebral cortex. Here we show that 3 NMDAR subunits, NR1, NR2A, and NR2B, are expressed in the human cerebral cortex during the second trimester of gestation, a period of intense neurogenesis and synaptogenesis. With increasing fetal age, expression of the NMDAR-encoding genes Grin1 (NR1) and Grin2a (NR2A) increased while Grin2b (NR2B) expression decreased...
September 24, 2016: Cerebral Cortex
Shauna L Houlihan, Alison A Lanctot, Yan Guo, Yuanyi Feng
Neuronal fate-restricted intermediate progenitors (IPs) are derived from the multipotent radial glia (RGs) and serve as the direct precursors for cerebral cortical neurons, but factors that control their neurogenic plasticity remain elusive. Here we report that IPs' neuron production is enhanced by abrogating filamin function, leading to the generation of periventricular neurons independent of normal neocortical neurogenesis and neuronal migration. Loss of Flna in neural progenitor cells (NPCs) led RGs to undergo changes resembling epithelial-mesenchymal transition (EMT) along with exuberant angiogenesis that together changed the microenvironment and increased neurogenesis of IPs...
September 24, 2016: ELife
Betty Freret-Hodara, Yi Cui, Amélie Griveau, Lisa Vigier, Yoko Arai, Jonathan Touboul, Alessandra Pierani
Loss of neurons in the neocortex is generally thought to result in a final reduction of cerebral volume. Yet, little is known on how the developing cerebral cortex copes with death of early-born neurons. Here, we tackled this issue by taking advantage of a transgenic mouse model in which, from early embryonic stages to mid-corticogenesis, abundant apoptosis is induced in the postmitotic compartment. Unexpectedly, the thickness of the mutant cortical plate at E18.5 was normal, due to an overproduction of upper layer neurons at E14...
September 12, 2016: Cerebral Cortex
Alessandro Sessa, Ernesto Ciabatti, Daniela Drechsel, Luca Massimino, Gaia Colasante, Serena Giannelli, Takashi Satoh, Shizuo Akira, Francois Guillemot, Broccoli Vania
The T-box containing Tbr2 gene encodes for a transcription factor essential for the specification of the intermediate neural progenitors (INPs) originating the excitatory neurons of the cerebral cortex. However, its overall mechanism of action, direct target genes and cofactors remain unknown. Herein, we carried out global gene expression profiling combined with genome-wide binding site identification to determine the molecular pathways regulated by TBR2 in INPs. This analysis led to the identification of novel protein-protein interactions that control multiple features of INPs including cell-type identity, morphology, proliferation and migration dynamics...
September 6, 2016: Cerebral Cortex
Venkat Swaroop Achuta, Heli Grym, Noora Putkonen, Verna Louhivuori, Virve Kärkkäinen, Jari Koistinaho, Laurent Roybon, Maija L Castrén
Disrupted metabotropic glutamate receptor 5 (mGluR5) signaling is implicated in many neuropsychiatric disorders, including autism spectrum disorder, found in fragile X syndrome (FXS). Here we report that intracellular calcium responses to the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) are augmented, and calcium-dependent mGluR5-mediated mechanisms alter the differentiation of neural progenitors in neurospheres derived from human induced pluripotent FXS stem cells and the brains of mouse model of FXS...
July 13, 2016: Developmental Neurobiology
Tomohisa Toda, Yohei Shinmyo, Tung Anh Dinh Duong, Kosuke Masuda, Hiroshi Kawasaki
Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding...
2016: Scientific Reports
Kazuhiro Maeta, Hironori Edamatsu, Kaori Nishihara, Junji Ikutomo, Shymaa E Bilasy, Tohru Kataoka
Cerebral neocortex development in mammals requires highly orchestrated events involving proliferation, differentiation, and migration of neural progenitors and neurons. Rapgef2 and Rapgef6 constitute a unique family of guanine nucleotide exchange factors for Rap1 small GTPase, which is known to play crucial roles in migration of postmitotic neurons. We previously reported that conditional knockout of Rapgef2 in dorsal telencephalon (Rapgef2-cKO) resulted in the formation of an ectopic cortical mass (ECM) resembling that of subcortical band heterotopia...
May 2016: ENeuro
Anca B Mihalas, Gina E Elsen, Francesco Bedogni, Ray A M Daza, Kevyn A Ramos-Laguna, Sebastian J Arnold, Robert F Hevner
Intermediate progenitors (IPs) amplify the production of pyramidal neurons, but their role in selective genesis of cortical layers or neuronal subtypes remains unclear. Using genetic lineage tracing in mice, we find that IPs destined to produce upper cortical layers first appear early in corticogenesis, by embryonic day 11.5. During later corticogenesis, IP laminar fates are progressively limited to upper layers. We examined the role of Tbr2, an IP-specific transcription factor, in laminar fate regulation using Tbr2 conditional mutant mice...
June 28, 2016: Cell Reports
Sanjeeb Kumar Sahu, Alina Fritz, Neha Tiwari, Zsuzsa Kovacs, Alireza Pouya, Verena Wüllner, Pablo Bora, Teresa Schacht, Jan Baumgart, Sophie Peron, Benedikt Berninger, Vijay K Tiwari, Axel Methner
The human genomic locus for the transcription factor TOX3 has been implicated in susceptibility to restless legs syndrome and breast cancer in genome-wide association studies, but the physiological role of TOX3 remains largely unknown. We found Tox3 to be predominantly expressed in the developing mouse brain with a peak at embryonic day E14 where it co-localizes with the neural stem and progenitor markers Nestin and Sox2 in radial glia of the ventricular zone and intermediate progenitors of the subventricular zone...
July 2016: Biochimica et Biophysica Acta
Hong-Ru Chen, Hsien-Chia Juan, Yu-Hui Wong, Jin-Wu Tsai, Ming-Ji Fann
DNA damage response (DDR) pathways are critical for ensuring that replication stress and various types of DNA lesion do not perturb production of neural cells during development. Cdk12 maintains genomic stability by regulating expression of DDR genes. Mutant mice in whichCdk12is conditionally deleted in neural progenitor cells (NPCs) die after birth and exhibit microcephaly with a thinner cortical plate and an aberrant corpus callosum. We show that NPCs of mutant mice accumulate at G2 and M phase, and have lower expression of DDR genes, more DNA double-strand breaks and increased apoptosis...
April 12, 2016: Cerebral Cortex
Ashley M Driver, Lisa E Kratz, Richard I Kelley, Rolf W Stottmann
We previously reported a mutation in the cholesterol biosynthesis gene, hydroxysteroid (17-beta) dehydrogenase 7 (Hsd17b7(rudolph)), that results in striking embryonic forebrain dysgenesis. Here we describe abnormal patterns of neuroprogenitor proliferation in the mutant forebrain, namely, a decrease in mitotic cells within the ventricular zone (VZ) and an increase through the remainder of the cortex by E11.5. Further evidence suggests mutant cells undergo abnormal interkinetic nuclear migration (IKNM). Furthermore, intermediate progenitors are increased at the expense of apical progenitors by E12...
July 2016: Neurobiology of Disease
Maija L Castrén
The absence of fragile X mental retardation 1 protein (FMRP) results in fragile X syndrome (FXS) that is a common cause of intellectual disability and a variant of autism spectrum disorder. There is evidence that FMRP is involved in neurogenesis. FMRP is widely expressed throughout the embryonic brain development and its expression levels increases during neuronal differentiation. Cortical neural progenitors propagated from human fetal FXS brain show expression changes of genes which encode components of intracellular signal transduction cascades, including receptors, second messengers, and transduction factors...
2016: Frontiers in Bioscience (Scholar Edition)
Yanyan Wang, Natalia Surzenko, Walter B Friday, Steven H Zeisel
Maternal diets low in choline, an essential nutrient, increase the risk of neural tube defects and lead to low performance on cognitive tests in children. However, the consequences of maternal dietary choline deficiency for the development and structural organization of the cerebral cortex remain unknown. In this study, we fed mouse dams either control (CT) or low-choline (LC) diets and investigated the effects of choline on cortical development in the offspring. As a result of a low choline supply between embryonic day (E)11 and E17 of gestation, the number of 2 types of cortical neural progenitor cells (NPCs)-radial glial cells and intermediate progenitor cells-was reduced in fetal brains (P< 0...
April 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sophie Laguesse, Catherine Creppe, Danny D Nedialkova, Pierre-Paul Prévot, Laurence Borgs, Sandra Huysseune, Bénédicte Franco, Guérin Duysens, Nathalie Krusy, Gabsang Lee, Nicolas Thelen, Marc Thiry, Pierre Close, Alain Chariot, Brigitte Malgrange, Sebastian A Leidel, Juliette D Godin, Laurent Nguyen
The cerebral cortex contains layers of neurons sequentially generated by distinct lineage-related progenitors. At the onset of corticogenesis, the first-born progenitors are apical progenitors (APs), whose asymmetric division gives birth directly to neurons. Later, they switch to indirect neurogenesis by generating intermediate progenitors (IPs), which give rise to projection neurons of all cortical layers. While a direct lineage relationship between APs and IPs has been established, the molecular mechanism that controls their transition remains elusive...
December 7, 2015: Developmental Cell
Ashlie A Tronnes, Jenna Koschnitzky, Ray Daza, Jane Hitti, Jan Marino Ramirez, Robert Hevner
Our objective was to determine if progesterone pretreatment could ameliorate the detrimental effects of lipopolysaccharide (LPS)-induced inflammation on cortical neurogenesis. Timed pregnant mouse dams (n = 8) were given intraperitoneal injections of progesterone (42 mg/kg) or vehicle on embryonic day 17.5. Two hours later, mice were given intraperitoneal LPS (140 μg/kg) or vehicle. Mice were sacrificed 16 hours later on embryonic day 18. Two-color immunofluorescence was performed with primary antibodies T-box transcription factor 2 (Tbr2), ionized calcium binding adapter molecule 1 (Iba1), cleaved caspase 3 (CC3), and 5-bromo-2'-deoxyuridine (BrdU)...
June 2016: Reproductive Sciences
Lauren F Harkin, Dianne Gerrelli, Diana C Gold Diaz, Chloe Santos, Ayman Alzu'bi, Caroline A Austin, Gavin J Clowry
TOP2A and TOP2B are type II topoisomerase enzymes that have important but distinct roles in DNA replication and RNA transcription. Recently, TOP2B has been implicated in the transcription of long genes in particular that play crucial roles in neural development and are susceptible to mutations contributing to neurodevelopmental conditions such as autism and schizophrenia. This study maps their expression in the early foetal human telencephalon between 9 and 12 post-conceptional weeks. TOP2A immunoreactivity was restricted to cell nuclei of the proliferative layers of the cortex and ganglionic eminences (GE), including the ventricular zone and subventricular zone (SVZ) closely matching expression of the proliferation marker KI67...
March 2016: Journal of Anatomy
Kosuke Masuda, Tomohisa Toda, Yohei Shinmyo, Haruka Ebisu, Yoshio Hoshiba, Mayu Wakimoto, Yoshie Ichikawa, Hiroshi Kawasaki
One of the most prominent features of the cerebral cortex of higher mammals is the presence of gyri. Because malformations of the cortical gyri are associated with severe disability in brain function, the mechanisms underlying malformations of the cortical gyri have been of great interest. Combining gyrencephalic carnivore ferrets and genetic manipulations using in utero electroporation, here we successfully recapitulated the cortical phenotypes of thanatophoric dysplasia (TD) by expressing fibroblast growth factor 8 in the ferret cerebral cortex...
2015: Scientific Reports
Philipp Abe, Zoltán Molnár, Yi-Shiuan Tzeng, Dar-Ming Lai, Sebastian J Arnold, Ralf Stumm
Glutamatergic principal neurons, GABAergic interneurons and thalamocortical axons (TCAs) are essential elements of the cerebrocortical network. Principal neurons originate locally from radial glia and intermediate progenitors (IPCs), whereas interneurons and TCAs are of extrinsic origin. Little is known how the assembly of these elements is coordinated. C-X-C motif chemokine 12 (CXCL12), which is known to guide axons outside the neural tube and interneurons in the cortex, is expressed in the meninges and IPCs...
September 23, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Odessa R Yabut, Gloria Fernandez, Trung Huynh, Keejung Yoon, Samuel J Pleasure
Proper lineage progression and diversification of neural progenitor cells (NPCs) ensures the generation of projection neuron (PN) subtypes in the mammalian neocortex. Here, we show that Suppressor of Fused (Sufu) controls PN specification by maintaining the identity of NPCs in the embryonic neocortex. Deletion of Sufu in NPCs of the E10.5 mouse neocortex led to improper specification of progenitors and a reduction in intermediate progenitors (IPs) during corticogenesis. We found that Sufu deletion resulted in unstable Gli2 and Gli3 activity, leading to the ectopic activation of Sonic hedgehog (Shh) signaling...
September 29, 2015: Cell Reports
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