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https://www.readbyqxmd.com/read/28800615/pitx3-and-en1-determine-the-size-and-molecular-programming-of-the-dopaminergic-neuronal-pool
#1
Willemieke M Kouwenhoven, Lars von Oerthel, Marten P Smidt
Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28779972/critical-role-of-trpc1-in-thyroid-hormone-dependent-dopaminergic-neuron-development
#2
Chunhai Chen, Qinglong Ma, Ping Deng, Jianjing Yang, Lingling Yang, Min Lin, Zhengping Yu, Zhou Zhou
Thyroid hormones play a crucial role in midbrain dopaminergic (DA) neuron development. However, the underlying molecular mechanisms remain largely unknown. In this study, we revealed that thyroid hormone treatment evokes significant calcium entry through canonical transient receptor potential (TRPC) channels in ventral midbrain neural stem cells and this calcium signaling is essential for thyroid hormone-dependent DA neuronal differentiation. We also found that TRPC1 is the dominant TRPC channel expressed in ventral midbrain neural stem cells which responds to thyroid hormone...
August 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28713249/crispr-cas9-mediated-zebrafish-knock-in-as-a-novel-strategy-to-study-midbrain-hindbrain-boundary-development
#3
Gokul Kesavan, Avinash Chekuru, Anja Machate, Michael Brand
The midbrain-hindbrain boundary (MHB) acts as an organizer and controls the fate of neighboring cells to develop into either mesencephalic (midbrain) or metencephalic (hindbrain) cells by secreting signaling molecules like Wnt1 and Fgf8. The zebrafish is an excellent vertebrate model for studying MHB development due to the ease of gene manipulation and the possibility of following cellular dynamics and morphogenetic processes using live imaging. Currently, only very few reporter and/or Cre-driver lines are available to study gene expression at the MHB, hampering the understanding of MHB development, and traditional transgenic technologies using promoter/enhancer fragments or bacterial artificial chromosome (BAC)-mediated transgenesis often do not faithfully recapitulate endogenous expression patterns...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#4
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28620275/genome-wide-target-analyses-of-otx2-homeoprotein-in-postnatal-cortex
#5
Akiko Sakai, Ryuichiro Nakato, Yiwei Ling, Xubin Hou, Norikazu Hara, Tomoya Iijima, Yuchio Yanagawa, Ryozo Kuwano, Shujiro Okuda, Katsuhiko Shirahige, Sayaka Sugiyama
Juvenile brain has a unique time window, or critical period, in which neuronal circuits are remodeled by experience. Mounting evidence indicates the importance of neuronal circuit rewiring in various neurodevelopmental disorders of human cognition. We previously showed that Otx2 homeoprotein, essential for brain formation, is recaptured during postnatal maturation of parvalbumin-positive interneurons (PV cells) to activate the critical period in mouse visual cortex. Cortical Otx2 is the only interneuron-enriched transcription factor known to regulate the critical period, but its downstream targets remain unknown...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28619944/early-life-stress-confers-lifelong-stress-susceptibility-in-mice-via-ventral-tegmental-area-otx2
#6
Catherine J Peña, Hope G Kronman, Deena M Walker, Hannah M Cates, Rosemary C Bagot, Immanuel Purushothaman, Orna Issler, Yong-Hwee Eddie Loh, Tin Leong, Drew D Kiraly, Emma Goodman, Rachael L Neve, Li Shen, Eric J Nestler
Early life stress increases risk for depression. Here we establish a "two-hit" stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA)-a brain reward region-to be in a depression-like state. We identify a role for the developmental transcription factor orthodenticle homeobox 2 (Otx2) as an upstream mediator of these enduring effects. Transient juvenile-but not adult-knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, whereas its overexpression reverses the effects of early life stress...
June 16, 2017: Science
https://www.readbyqxmd.com/read/28612405/a-comparative-transcriptomic-analysis-of-development-in-two-astyanax-cavefish-populations
#7
Bethany A Stahl, Joshua B Gross
Organisms that are isolated into extreme environments often evolve extreme phenotypes. However, global patterns of dynamic gene expression changes that accompany dramatic environmental changes remain largely unknown. The blind Mexican cavefish, Astyanax mexicanus, has evolved a number of severe cave-associated phenotypes including loss of vision and pigmentation, craniofacial bone fusions, increased fat storage, reduced sleep, and amplified nonvisual sensory systems. Interestingly, surface-dwelling forms have repeatedly entered different caves throughout Mexico, providing a natural set of "replicate" instances of cave isolation...
June 14, 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/28575744/decreased-neural-precursor-cell-pool-in-nadph-oxidase-2-deficiency-from-mouse-brain-to-neural-differentiation-of-patient-derived-ipsc
#8
Zeynab Nayernia, Marilena Colaianna, Natalia Robledinos-Antón, Eveline Gutzwiller, Frédérique Sloan-Béna, Elisavet Stathaki, Yousef Hibaoui, Antonio Cuadrado, Jürgen Hescheler, Marie-José Stasia, Tomo Saric, Vincent Jaquet, Karl-Heinz Krause
There is emerging evidence for the involvement of reactive oxygen species (ROS) in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD) patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC). High levels of NOX2 were found in mouse adult neurogenic regions...
April 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28514120/mouth-development
#9
REVIEW
Justin Chen, Laura A Jacox, Francesca Saldanha, Hazel Sive
A mouth is present in all animals, and comprises an opening from the outside into the oral cavity and the beginnings of the digestive tract to allow eating. This review focuses on the earliest steps in mouth formation. In the first half, we conclude that the mouth arose once during evolution. In all animals, the mouth forms from ectoderm and endoderm. A direct association of oral ectoderm and digestive endoderm is present even in triploblastic animals, and in chordates, this region is known as the extreme anterior domain (EAD)...
May 17, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28493069/comparison-of-molecular-marker-expression-in-early-zebrafish-brain-development-following-chronic-ethanol-or-morpholino-treatment
#10
Chengjin Zhang, Oswald Boa-Amponsem, Gregory J Cole
This study was undertaken to ascertain whether defined markers of early zebrafish brain development are affected by chronic ethanol exposure or morpholino knockdown of agrin, sonic hedgehog, retinoic acid, and fibroblast growth factors, four signaling molecules that are suggested to be ethanol sensitive. Zebrafish embryos were exposed to 2% ethanol from 6 to 24 hpf or injected with agrin, shha, aldh1a3, or fgf8a morpholinos. In situ hybridization was employed to analyze otx2, pax6a, epha4a, krx20, pax2a, fgf8a, wnt1, and eng2b expression during early brain development...
August 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28476222/pituitary-hypoplasia
#11
REVIEW
Mariam Gangat, Sally Radovick
This article summarizes pituitary development and function as well as specific mutations of genes encoding the following transcription factors: HESX1, LHX3, LHX4, POU1F1, PROP1, and OTX2. Although several additional genetic defects related to hypopituitarism have been identified, this article focuses on these selected factors, as they have been well described in the literature in terms of clinical characterization of affected patients and molecular mechanisms of action, and therefore, are very relevant to clinical practice...
June 2017: Endocrinology and Metabolism Clinics of North America
https://www.readbyqxmd.com/read/28455373/chip-seq-analysis-of-genomic-binding-regions-of-five-major-transcription-factors-highlights-a-central-role-for-zic2-in-the-mouse-epiblast-stem-cell-gene-regulatory-network
#12
Kazunari Matsuda, Tomoyuki Mikami, Shinya Oki, Hideaki Iida, Munazah Andrabi, Jeremy M Boss, Katsushi Yamaguchi, Shuji Shigenobu, Hisato Kondoh
To obtain insight into the transcription factor (TF)-dependent regulation of epiblast stem cells (EpiSCs), we performed ChIP-seq analysis of the genomic binding regions of five major TFs. Analysis of in vivo biotinylated ZIC2, OTX2, SOX2, POU5F1 and POU3F1 binding in EpiSCs identified several new features. (1) Megabase-scale genomic domains rich in ZIC2 peaks and genes alternate with those rich in POU3F1 but sparse in genes, reflecting the clustering of regulatory regions that act at short and long-range, which involve binding of ZIC2 and POU3F1, respectively...
June 1, 2017: Development
https://www.readbyqxmd.com/read/28424350/tau-haploinsufficiency-causes-prenatal-loss-of-dopaminergic-neurons-in-the-ventral-tegmental-area-and-reduction-of-transcription-factor-orthodenticle-homeobox-2-expression
#13
Meige Zheng, Luyan Jiao, Xiaolu Tang, Xianhong Xiang, Xiaomei Wan, Yan Yan, Xingjian Li, Guofeng Zhang, Yonglin Li, Bin Jiang, Huaibin Cai, Xian Lin
Homozygous tau knockout (Mapt(-/-)) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau in maintaining the survival of midbrain dopaminergic neurons (mDANs) during aging. However, it remains to be determined whether the microtubule-associated protein tau regulates the differentiation and survival of mDANs during embryonic developmental stages. Here, we show that tau haploinsufficiency in postnatal day 0 (P0) heterozygous (Mapt(+/-)) pups, but not a complete loss of tau in the Mapt(-/-) littermates, led to a significant reduction of DA neurons in the VTA...
April 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28401018/otx2-expression-contributes-to-proliferation-and-progression-in-myc-amplified-medulloblastoma
#14
REVIEW
Yining Lu, Collin M Labak, Neha Jain, Ian J Purvis, Maheedhara R Guda, Sarah E Bach, Andrew J Tsung, Swapna Asuthkar, Kiran K Velpula
Medulloblastoma is one of the most prevalent pediatric brain malignancies, accounting for approximately 20% of all primary CNS tumors in children under the age of 19. OTX2 is the member of a highly conserved family of bicoid-like homeodomain transcription factors responsible for the regulation of cerebellar development and of current investigational interest in the tumorigenesis of medulloblastoma. Recent studies have revealed that Group 3 and Group 4 medulloblastomas show marked overexpression of OTX2 with a concurrent amplification of the MYC and MYCN oncogenes, respectively, correlating with anaplasticity and unfavorable patient outcomes...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28388256/intrafamilial-variability-in-syndromic-microphthalmia-type-5-caused-by-a-novel-variation-in-otx2
#15
Puneeth H Somashekar, Anju Shukla, Katta M Girisha
BACKGROUND: Anophthalmia/microphthalmia/coloboma (MAC) spectrum encompasses the most severe malformations of the eye. Together, they have an incidence of 2 in 10,000 births and can be unilateral or bilateral. These disorders are genetically heterogeneous. MATERIALS AND METHODS: We ascertained a large three-generation family with multiple members showing variable phenotypes of syndromic microphthalmia. Exome sequencing was performed for the proband and his affected maternal aunt...
April 7, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28373687/genetic-otx2-mis-localization-delays-critical-period-plasticity-across-brain-regions
#16
H H C Lee, C Bernard, Z Ye, D Acampora, A Simeone, A Prochiantz, A A Di Nardo, T K Hensch
No abstract text is available yet for this article.
April 4, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28348423/otx1-and-otx2-as-possible-molecular-markers-of-sinonasal-carcinomas-and-olfactory-neuroblastomas
#17
Cristina Pirrone, Anna M Chiaravalli, Alessandro Marando, Andrea Conti, Alessia Rainero, Andrea Pistochini, Francesco Lo Curto, Francesco Pasquali, Paolo Castelnuovo, Carlo Capella, Giovanni Porta
OTX Homeobox genes are involved in embryonic morphogenesis and in the development of olfactory epithelium in adult. Mutations occurring in the OTX genes are reported to be associated to tumorigenisis in human. No reports correlate the expression of OTX genes and neoplasms of the nasal cavity. Thus, through immunohistochemical and Real-time PCR analysis we investigated OTX1 and OTX2 expression in the more frequent types of nasal and sinonasal tumours. Variable expression of both genes were found in normal sinonasal mucosa and in tumours...
February 9, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28297587/efficiently-specified-ventral-midbrain-dopamine-neurons-from-human-pluripotent-stem-cells-under-xeno-free-conditions-restore-motor-deficits-in-parkinsonian-rodents
#18
Jonathan C Niclis, Carlos W Gantner, Walaa F Alsanie, Stuart J McDougall, Chris R Bye, Andrew G Elefanty, Edouard G Stanley, John M Haynes, Colin W Pouton, Lachlan H Thompson, Clare L Parish
Recent studies have shown evidence for the functional integration of human pluripotent stem cell (hPSC)-derived ventral midbrain dopamine (vmDA) neurons in animal models of Parkinson's disease. Although these cells present a sustainable alternative to fetal mesencephalic grafts, a number of hurdles require attention prior to clinical translation. These include the persistent use of xenogeneic reagents and challenges associated with scalability and storage of differentiated cells. In this study, we describe the first fully defined feeder- and xenogeneic-free protocol for the generation of vmDA neurons from hPSCs and utilize two novel reporter knock-in lines (LMX1A-eGFP and PITX3-eGFP) for in-depth in vitro and in vivo tracking...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28288836/temporal-profiling-of-photoreceptor-lineage-gene-expression-during-murine-retinal-development
#19
Tooka Aavani, Nobuhiko Tachibana, Valerie Wallace, Jeffrey Biernaskie, Carol Schuurmans
Rod and cone photoreceptors are photosensitive cells in the retina that convert light to electrical signals that are transmitted to visual processing centres in the brain. During development, cones and rods are generated from a common pool of multipotent retinal progenitor cells (RPCs) that also give rise to other retinal cell types. Cones and rods differentiate in two distinct waves, peaking in mid-embryogenesis and the early postnatal period, respectively. As RPCs transition from making cones to generating rods, there are changes in the expression profiles of genes involved in photoreceptor cell fate specification and differentiation...
January 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28285945/hanging-drop-culture-enhances-differentiation-of-human-adipose-derived-stem-cells-into-anterior-neuroectodermal-cells-using-small-molecules
#20
Noushin Amirpour, Shahnaz Razavi, Ebrahim Esfandiari, Batoul Hashemibeni, Mohammad Kazemi, Hossein Salehi
Inspired by in vivo developmental process, several studies were conducted to design a protocol for differentiating of mesenchymal stem cells into neural cells in vitro. Human adipose-derived stem cells (hADSCs) as mesenchymal stem cells are a promising source for this purpose. At current study, we applied a defined neural induction medium by using small molecules for direct differentiation of hADSCs into anterior neuroectodermal cells. Anterior neuroectodermal differentiation of hADSCs was performed by hanging drop and monolayer protocols...
March 7, 2017: International Journal of Developmental Neuroscience
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