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Shh and cerebral cortex

Fani Memi, Nada Zecevic, Nevena Radonjić
Sonic Hedgehog (Shh) plays an instrumental role in brain development, fine-tuning processes such as cell proliferation, patterning, and fate specification. Although, mutations in the SHH pathway in humans are associated with various neurodevelopmental disorders, ranging from holoprosencephaly to schizophrenia, its expression pattern in the developing human brain is not well established. We now determined the previously not reported wide expression of SHH in the human fetal cerebral cortex during most of the gestation period (10-40 gestational weeks)...
February 28, 2018: Brain Structure & Function
Almudena Martinez-Ferre, Cosme Lloret-Quesada, Nilima Prakash, Wolfgang Wurst, John L R Rubenstein, Salvador Martinez
The establishment of the brain structural complexity requires a precisely orchestrated interplay between extrinsic and intrinsic signals modulating cellular mechanisms to guide neuronal differentiation. However, little is known about the nature of these signals in the diencephalon, a complex brain region that processes and relays sensory and motor information to and from the cerebral cortex and subcortical structures. Morphogenetic signals from brain organizers regulate histogenetic processes such as cellular proliferation, migration, and differentiation...
July 2016: Brain Structure & Function
O V Chechneva, F Mayrhofer, D J Daugherty, R G Krishnamurty, P Bannerman, D E Pleasure, W Deng
Ischemic stroke occurs as a result of blood supply interruption to the brain causing tissue degeneration, patient disabilities or death. Currently, treatment of ischemic stroke is limited to thrombolytic therapy with a narrow time window of administration. The sonic hedgehog (Shh) signaling pathway has a fundamental role in the central nervous system development, but its impact on neural cell survival and tissue regeneration/repair after ischemic stroke has not been well investigated. Here we report the neuroprotective properties of a small-molecule agonist of the Shh co-receptor Smoothened, purmorphamine (PUR), in the middle cerebral artery occlusion model of ischemic stroke...
October 23, 2014: Cell Death & Disease
Amanda J Mierzwa, Genevieve M Sullivan, Laurel A Beer, Sohyun Ahn, Regina C Armstrong
The regenerative capacity of the central nervous system must be optimized to promote repair following traumatic brain injury (TBI) and may differ with the site and form of damage. Sonic hedgehog (Shh) maintains neural stem cells and promotes oligodendrogenesis. We examined whether Shh signaling contributes to neuroblast (doublecortin) or oligodendrocyte progenitor (neural/glial antigen 2 [NG2]) responses in two distinct TBI models. Shh-responsive cells were heritably labeled in vivo using Gli1-CreER(T2);R26-YFP bitransgenic mice with tamoxifen administration on Days 2 and 3 post-TBI...
2014: ASN Neuro
Nevena V Radonjić, Juan A Ortega, Fani Memi, Krista Dionne, Igor Jakovcevski, Nada Zecevic
The complex structure and function of the cerebral cortex critically depend on the balance of excitation and inhibition provided by the pyramidal projection neurons and GABAergic interneurons, respectively. The calretinin-expressing (CalR(+)) cell is a subtype of GABAergic cortical interneurons that is more prevalent in humans than in rodents. In rodents, CalR(+) interneurons originate in the caudal ganglionic eminence (CGE) from Gsx2(+) progenitors, but in humans it has been suggested that a subpopulation of CalR(+) cells can also be generated in the cortical ventricular/subventricular zone (VZ/SVZ)...
2014: Frontiers in Neuroanatomy
Alfonso Massimiliano Ferrara, Xiao-Hui Liao, Pilar Gil-Ibáñez, Juan Bernal, Roy E Weiss, Alexandra M Dumitrescu, Samuel Refetoff
Monocarboxylate transporter 8 (MCT8) deficiency causes severe X-linked intellectual and neuropsychological impairment associated with abnormal thyroid function tests (TFTs) producing thyroid hormone (TH) deprivation in brain and excess in peripheral tissues. The TH analog diiodothyropropionic acid (DITPA) corrected the TFTs abnormalities and hypermetabolism of MCT8-deficient children but did not improve the neurological phenotype. The latter result was attributed to the late initiation of treatment. Therefore, we gave DITPA to pregnant mice carrying Mct8-deficient embryos to determine whether DITPA, when given prenatally, crosses the placenta and affects the serum TFTs and cerebral cortex of embryos...
October 2014: Endocrinology
Qing-Shan Liu, Shu-Juan Zhuang, Ke-Qin Li, Xu Li
Neural stem cells in brains have capacities of proliferation and differentiation, which is very critical to rebuild the cerebral cortex functions. Therefore, it is of great importance to find key targets and network pathways that regulate the proliferation of neural stem cells, which is also a pressing problem in the medical circle. With the Notch pathway as the core of the network, this paper summarized the advance of the bimolecular network system composed of Wnt, Shh, EGFR, cytokines and Notch signal, and analyzed such key nodes as Notch receptor, CBF1, NICD, Hesl, which may become potential targets of new-type drugs in the future...
February 2014: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Sabrina Mioranzza, Fernanda Nunes, Daniela M Marques, Gabriela T Fioreze, Andréia S Rocha, Paulo Henrique S Botton, Marcelo S Costa, Lisiane O Porciúncula
Caffeine is the psychostimulant most consumed worldwide. However, little is known about its effects during fetal brain development. In this study, adult female Wistar rats received caffeine in drinking water (0.1, 0.3 and 1.0 g/L) during the active cycle in weekdays, two weeks before mating and throughout pregnancy. Cerebral cortex and hippocampus from embryonic stages 18 or 20 (E18 or E20, respectively) were collected for immunodetection of the following synaptic proteins: brain-derived neurotrophic factor (BDNF), TrkB receptor, Sonic Hedgehog (Shh), Growth Associated Protein 43 (GAP-43) and Synaptosomal-associated Protein 25 (SNAP-25)...
August 2014: International Journal of Developmental Neuroscience
Heejung Moon, Jieun Song, Jeong-Oh Shin, Hankyu Lee, Hong-Kyung Kim, Jonathan T Eggenschwiller, Jinwoong Bok, Hyuk Wan Ko
Endocrine-cerebro-osteodysplasia (ECO) syndrome is a recessive genetic disorder associated with multiple congenital defects in endocrine, cerebral, and skeletal systems that is caused by a missense mutation in the mitogen-activated protein kinase-like intestinal cell kinase (ICK) gene. In algae and invertebrates, ICK homologs are involved in flagellar formation and ciliogenesis, respectively. However, it is not clear whether this role of ICK is conserved in mammals and how a lack of functional ICK results in the characteristic phenotypes of human ECO syndrome...
June 10, 2014: Proceedings of the National Academy of Sciences of the United States of America
Geissy L L Araújo, Jessica A M Araújo, Timm Schroeder, Adriano B L Tort, Marcos R Costa
The morphogen Sonic Hedgehog (SHH) plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro...
2014: Frontiers in Cellular Neuroscience
Pilar Gil-Ibáñez, Juan Bernal, Beatriz Morte
The effects of thyroid hormone on brain development and function are largely mediated by the binding of 3,5,3'-triiodo-L-thyronine (T3) to its nuclear receptors (TR) to regulate positively or negatively gene expression. We have analyzed by quantitative polymerase chain reaction the effect of T3 on primary cultured cells from the embryonic mouse cerebral cortex, on the expression of Hr, Klf9, Shh, Dio3, Aldh1a1, and Aldh1a3. In particular we focused on T3 receptor specificity, and on the crosstalk between T3, retinoic acid and dexamethasone...
2014: PloS One
Xiaoli Wang, Yansong Zhao, Xin Wang
Transplantation of umbilical cord blood mononuclear cells (UCBMC) promotes the proliferation of endogenous neural stem cells (NSCs), but it has been unclear whether the proliferating NSCs can differentiate into mature neural cells. Therefore, we explored the effects of UCBMC transplantation on the differentiation of endogenous NSCs and their underlying mechanisms. Seven-day-old Sprague-Dawley rats underwent left carotid ligation followed by hypoxic stress. UCBMC were transplanted 24h after hypoxia ischemia (HI)...
April 29, 2014: Brain Research
Mallika Chatterjee, Qiuxia Guo, Sabrina Weber, Steffen Scholpp, James Yh Li
BACKGROUND: The habenula and the thalamus are two critical nodes in the forebrain circuitry and they connect the midbrain and the cerebral cortex in vertebrates. The habenula is derived from the epithalamus and rests dorsally to the thalamus. Both epithalamus and thalamus arise from a single diencephalon segment called prosomere (p)2. Shh is expressed in the ventral midline of the neural tube and in the mid-diencephalic organizer (MDO) at the zona limitans intrathalamica between thalamus and prethalamus...
February 14, 2014: BMC Biology
Sandrine L Anne, Eve-Ellen Govek, Olivier Ayrault, Jee Hae Kim, Xiaodong Zhu, David A Murphy, Linda Van Aelst, Martine F Roussel, Mary E Hatten
During normal cerebellar development, the remarkable expansion of granule cell progenitors (GCPs) generates a population of granule neurons that outnumbers the total neuronal population of the cerebral cortex, and provides a model for identifying signaling pathways that may be defective in medulloblastoma. While many studies focus on identifying pathways that promote growth of GCPs, a critical unanswered question concerns the identification of signaling pathways that block mitogenic stimulation and induce early steps in differentiation...
2013: PloS One
José Javier Otero, Ilona Kalaszczynska, Wojciech Michowski, Michael Wong, Patrick Edwin Gygli, Hamza Numan Gokozan, Amélie Griveau, Junko Odajima, Catherine Czeisler, Fay Patsy Catacutan, Alice Murnen, Ulrich Schüller, Piotr Sicinski, David Rowitch
The mammalian genome encodes two A-type cyclins, which are considered potentially redundant yet essential regulators of the cell cycle. Here, we tested requirements for cyclin A1 and cyclin A2 function in cerebellar development. Compound conditional loss of cyclin A1/A2 in neural progenitors resulted in severe cerebellar hypoplasia, decreased proliferation of cerebellar granule neuron progenitors (CGNP), and Purkinje (PC) neuron dyslamination. Deletion of cyclin A2 alone showed an identical phenotype, demonstrating that cyclin A1 does not compensate for cyclin A2 loss in neural progenitors...
January 15, 2014: Developmental Biology
Tandis Vazin, K Aurelia Ball, Hui Lu, Hyungju Park, Yasaman Ataeijannati, Teresa Head-Gordon, Mu-ming Poo, David V Schaffer
Alzheimer's disease (AD) is among the most prevalent forms of dementia affecting the aging population, and pharmacological therapies to date have not been successful in preventing disease progression. Future therapeutic efforts may benefit from the development of models that enable basic investigation of early disease pathology. In particular, disease-relevant models based on human pluripotent stem cells (hPSCs) may be promising approaches to assess the impact of neurotoxic agents in AD on specific neuronal populations and thereby facilitate the development of novel interventions to avert early disease mechanisms...
February 2014: Neurobiology of Disease
Tao Li, Jie Zhang, Rong-Yao Liu, Zhi-Gang Lian, Xiao-Lin Chen, Li Ma, Hao-Min Sun, Yuan-Li Zhao
Previous studies have demonstrated that the sonic hedgehog (Shh) pathway plays a neuro-protective role. However, whether the Shh pathway is induced by subarachnoid hemorrhage (SAH) has not been investigated. We sought to investigate Shh activation in the cortex in the early stage of SAH, and assessed the effect of cyclopamine (a specific inhibitor of the Shh pathway) on Shh pathway regulation and evaluated the impact of cyclopamine on SAH. We found that the Shh pathway was up-regulated in the cortex after SAH, and that blocking the Shh pathway increased cell apoptosis...
September 27, 2013: Neuroscience Letters
Muriel Kmet, Chao Guo, Carina Edmondson, Bin Chen
Understanding how neuronal diversity is achieved within the cerebral cortex remains a major challenge in neuroscience. The advent of human embryonic stem cells (hESCs) as a model system provides a unique opportunity to study human corticogenesis in vitro and to identify the mechanisms that promote neuronal differentiation to achieve neuronal diversity in human brain. The transcription factor Fezf2 is necessary and sufficient for the specification of subcerebral projection neurons in mouse. However, its function during human corticogenesis is poorly understood...
2013: PloS One
Asif M Maroof, Sotirios Keros, Jennifer A Tyson, Shui-Wang Ying, Yosif M Ganat, Florian T Merkle, Becky Liu, Adam Goulburn, Edouard G Stanley, Andrew G Elefanty, Hans Ruedi Widmer, Kevin Eggan, Peter A Goldstein, Stewart A Anderson, Lorenz Studer
Human pluripotent stem cells are a powerful tool for modeling brain development and disease. The human cortex is composed of two major neuronal populations: projection neurons and local interneurons. Cortical interneurons comprise a diverse class of cell types expressing the neurotransmitter GABA. Dysfunction of cortical interneurons has been implicated in neuropsychiatric diseases, including schizophrenia, autism, and epilepsy. Here, we demonstrate the highly efficient derivation of human cortical interneurons in an NKX2...
May 2, 2013: Cell Stem Cell
Swetlana Sirko, Gwendolyn Behrendt, Pia Annette Johansson, Pratibha Tripathi, Marcos Costa, Sarah Bek, Christophe Heinrich, Steffen Tiedt, Dilek Colak, Martin Dichgans, Isabel Rebekka Fischer, Nikolaus Plesnila, Matthias Staufenbiel, Christian Haass, Marina Snapyan, Armen Saghatelyan, Li-Huei Tsai, André Fischer, Kay Grobe, Leda Dimou, Magdalena Götz
As a result of brain injury, astrocytes become activated and start to proliferate in the vicinity of the injury site. Recently, we had demonstrated that these reactive astrocytes, or glia, can form self-renewing and multipotent neurospheres in vitro. In the present study, we demonstrate that it is only invasive injury, such as stab wounding or cerebral ischemia, and not noninvasive injury conditions, such as chronic amyloidosis or induced neuronal death, that can elicit this increase in plasticity. Furthermore, we find that Sonic hedgehog (SHH) is the signal that acts directly on the astrocytes and is necessary and sufficient to elicit the stem cell response both in vitro and in vivo...
April 4, 2013: Cell Stem Cell
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