scholarly journals Expression Profile of Sonic Hedgehog Pathway Members in the Developing Human Fetal Brain

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Julia Tichy ◽  
Jenny Zinke ◽  
Benedikt Bunz ◽  
Richard Meyermann ◽  
Patrick N. Harter ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Subventricular Zone ◽  
Granular Layer ◽  
Ventricular Zone ◽  
Fetal Brain ◽  
Cortical Plate ◽  
Temporal Expression ◽  
Spatiotemporal Expression ◽  
Pathway Expression ◽  
Proliferation And Differentiation

The Sonic Hedgehog (SHH) pathway plays a central role in the developing mammalian CNS. In our study, we aimed to investigate the spatiotemporalSHHpathway expression pattern in human fetal brains. We analyzed 22 normal fetal brains for Shh, Patched, Smoothened, and Gli1-3 expression by immunohistochemistry. In the telencephalon, strongest expression of Shh, Smoothened, and Gli2 was found in the cortical plate (CP) and ventricular zone. Patched was strongly upregulated in the ventricular zone and Gli1 in the CP. In the cerebellum,SHHpathway members were strongly expressed in the external granular layer (EGL).SHHpathway members significantly decreased over time in the ventricular and subventricular zone and in the cerebellar EGL, while increasing levels were found in more superficial telencephalic layers. Our findings show thatSHHpathway members are strongly expressed in areas important for proliferation and differentiation and indicate a temporal expression gradient in telencephalic and cerebellar layers probably due to decreased proliferation of progenitor cells and increased differentiation. Our data about the spatiotemporal expression ofSHHpathway members in the developing human brain serves as a base for the understanding of both normal and pathological CNS development.

scholarly journals A Comparison of the Patterns of Migration and the Destinations of Homotopically Transplanted Neonatal Subventricular Zone Cells and Heterotopically Transplanted Telencephalic Ventricular Zone Cells

1996 ◽  
Vol 173 (2) ◽  
pp. 459-474 ◽  
Author(s):  
Tanja Zigova ◽  
Ranjita Betarbet ◽  
Betty Jean Soteres ◽  
Susannah Brock ◽  
Roy A.E. Bakay ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Ventricular Zone

Spatiotemporal expression of NDRG2 in the human fetal brain

2019 ◽  
Vol 221 ◽  
pp. 148-155 ◽  
Author(s):  
Peng-Peng Jin ◽  
Feng Xia ◽  
Bin-Fang Ma ◽  
Zhen Li ◽  
Guo-Feng Zhang ◽  
...  
Keyword(s):  
Fetal Brain ◽  
Human Fetal Brain ◽  
Spatiotemporal Expression

scholarly journals Neuroprotective effects of dexmedetomidine on the ketamine-induced disruption of the proliferation and differentiation of developing neural stem cells in the subventricular zone

2020 ◽  
Author(s):  
Huanhuan Sha ◽  
Peipei Peng ◽  
Bing Li ◽  
Guohua Wei ◽  
Juan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Pediatric Anesthesia ◽  
Brdu Incorporation ◽  
Control Group ◽  
Neuroprotective Effects ◽  
Proliferation And Differentiation ◽  
Ketamine Anesthesia ◽  
Β Tubulin

Abstract Background: Recently, the number of neonatal patients receiving surgery under general anesthesia has increased. Ketamine disrupts the proliferation and differentiation of developing neural stem cells (NSCs). Therefore, the safe use of ketamine in pediatric anesthesia has been an issue of increasing concern among anesthesiologists and the children’s parents. Dexmedetomidine (DEX) is widely used in sedation, as an antianxiety agent and for analgesia. DEX has recently been shown to provide neuroprotection against anesthetic-induced neurotoxicity in the developing brain. The aim of this in vivo study was to investigate whether DEX exerted neuroprotective effects on the proliferation and differentiation of NSCs in the subventricular zone (SVZ) following neonatal ketamine exposure. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley rats were equally divided into the following 5 groups: Control group (n=8), Ketamine group (n=8), 1 μg/kg DEX+Ketamine group (n=8), 5 μg/kg DEX+Ketamine group (n=8) and 10 μg/kg DEX+Ketamine group (n=8). The proliferation and differentiation of NSCs in the SVZ were assessed using immunostaining with BrdU incorporation. The levels of Nestin and β-tubulin III in the SVZ were measured using Western blot analyses. Apoptosis was assessed by detecting the levels of the cleaved caspase-3 protein using Western blotting. Results: Neonatal ketamine exposure significantly inhibited NSC proliferation and astrocytic differentiation in the SVZ, and neuronal differentiation was markedly increased. Furthermore, pretreatment with moderate (5 μg/kg) or high doses (10 μg/kg) of DEX reversed the ketamine-induced disturbances in the proliferation and differentiation of NSCs. Meanwhile, neonatal ketamine exposure significantly decreased the expression of Nestin and increased the expression of β-tubulin III in the SVZ compared with the Control group. Treatment with 10 μg/kg DEX notably reversed the ketamine-induced changes in the levels of Nestin and β-tubulin III. In addition, a pretreatment with 10 μg/kg DEX before ketamine anesthesia prevented apoptosis in the SVZ induced by neonatal ketamine exposure. Conclusions: Based on our findings, DEX may exert neuroprotective effects on the proliferation and differentiation of NSCs in the SVZ of neonatal rats in a repeated ketamine anesthesia model.

scholarly journals Dab2IP Regulates Neuronal Positioning, Rap1 Activity and Integrin Signaling in the Developing Cortex

2015 ◽  
Vol 37 (2) ◽  
pp. 131-141 ◽  
Author(s):  
Shuhong Qiao ◽  
Ramin Homayouni
Keyword(s):  
Brain Development ◽  
Cortical Neurons ◽  
Ventricular Zone ◽  
Physiological Role ◽  
Immunohistochemical Analysis ◽  
Superficial Layer ◽  
Tumor Formation ◽  
Intermediate Zone ◽  
Cortical Plate ◽  
Integrin Signaling

Dab2IP (DOC-2/DAB2 interacting protein) is a GTPase-activating protein which is involved in various aspects of brain development in addition to its roles in tumor formation and apoptosis in other systems. In this study, we carefully examined the expression profile of Dab2IP and investigated its physiological role during brain development using a Dab2IP-knockdown (KD) mouse model created by retroviral insertion of a LacZ-encoding gene-trapping cassette. LacZ staining revealed that Dab2IP is expressed in the ventricular zone as well as the cortical plate and the intermediate zone. Immunohistochemical analysis showed that Dab2IP protein is localized in the leading process and proximal cytoplasmic regions of migrating neurons in the intermediate zone. Bromodeoxyuridine birth dating experiments in combination with immunohistochemical analysis using layer-specific markers showed that Dab2IP is important for proper positioning of a subset of layer II-IV neurons in the developing cortex. Notably, neuronal migration was not completely disrupted in the cerebral cortex of Dab2IP-KD mice and disruption of migration was not strictly layer specific. Previously, we found that Dab2IP regulates multipolar transition in cortical neurons. Others have shown that Rap1 regulates the transition from multipolar to bipolar morphology in migrating postmitotic neurons through N-cadherin signaling and somal translocation in the superficial layer of the cortical plate through integrin signaling. Therefore, we examined whether Rap1 and integrin signaling were affected in Dab2IP-KD brains. We found that Dab2IP-KD resulted in higher levels of activated Rap1 and integrin in the developing cortex. Taken together, our results suggest that Dab2IP plays an important role in the migration and positioning of a subpopulation of later-born (layers II-IV) neurons, likely through the regulation of Rap1 and integrin signaling.

Neutralization of Nerve Growth Factor Impairs Proliferation and Differentiation of Adult Neural Progenitors in the Subventricular Zone

Stem Cells ◽  
2014 ◽  
Vol 32 (9) ◽  
pp. 2516-2528 ◽  
Author(s):  
Raffaella Scardigli ◽  
Paolo Capelli ◽  
Domenico Vignone ◽  
Rossella Brandi ◽  
Marcello Ceci ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Subventricular Zone ◽  
Neural Progenitors ◽  
Nerve Growth ◽  
Proliferation And Differentiation

Hedgehog signals regulate multiple aspects of gastrointestinal development

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2763-2772 ◽  
Author(s):  
M. Ramalho-Santos ◽  
D.A. Melton ◽  
A.P. McMahon
Keyword(s):  
Gastrointestinal Tract ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Target Genes ◽  
Critical Role ◽  
Indian Hedgehog ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mesodermal Origin ◽  
Gut Endoderm

The gastrointestinal tract develops from the embryonic gut, which is composed of an endodermally derived epithelium surrounded by cells of mesodermal origin. Cell signaling between these two tissue layers appears to play a critical role in coordinating patterning and organogenesis of the gut and its derivatives. We have assessed the function of Sonic hedgehog and Indian hedgehog genes, which encode members of the Hedgehog family of cell signals. Both are expressed in gut endoderm, whereas target genes are expressed in discrete layers in the mesenchyme. It was unclear whether functional redundancy between the two genes would preclude a genetic analysis of the roles of Hedgehog signaling in the mouse gut. We show here that the mouse gut has both common and separate requirements for Sonic hedgehog and Indian hedgehog. Both Sonic hedgehog and Indian hedgehog mutant mice show reduced smooth muscle, gut malrotation and annular pancreas. Sonic hedgehog mutants display intestinal transformation of the stomach, duodenal stenosis (obstruction), abnormal innervation of the gut and imperforate anus. Indian hedgehog mutants show reduced epithelial stem cell proliferation and differentiation, together with features typical of Hirschsprung's disease (aganglionic colon). These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations.

scholarly journals Impact of Sonic Hedgehog Pathway Expression on Outcome in HPV Negative Head and Neck Carcinoma Patients after Surgery and Adjuvant Radiotherapy

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0167665 ◽  
Author(s):  
Elisabeth Enzenhofer ◽  
Thomas Parzefall ◽  
Georg Haymerle ◽  
Sven Schneider ◽  
Lorenz Kadletz ◽  
...  
Keyword(s):  
Head And Neck ◽  
Sonic Hedgehog ◽  
Adjuvant Radiotherapy ◽  
Head And Neck Carcinoma ◽  
Hedgehog Pathway ◽  
Sonic Hedgehog Pathway ◽  
Pathway Expression ◽  
Neck Carcinoma

scholarly journals Maternal Leukemia Inhibitory Factor (LIF) Promotes Fetal Neurogenesis via a LIF-ACTH-LIF Signaling Relay Pathway

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1853-1862 ◽  
Author(s):  
Eriko Simamura ◽  
Hiroki Shimada ◽  
Nobuaki Higashi ◽  
Maimi Uchishiba ◽  
Hiroki Otani ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Leukemia Inhibitory Factor ◽  
Ventricular Zone ◽  
Fetal Brain ◽  
Inhibitory Factor ◽  
Neuronal Progenitor ◽  
Nucleated Red Blood Cells ◽  
Show Evidence

Leukemia inhibitory factor (LIF) promotes the proliferation of neuronal progenitor cells in the cerebrum. However, it remains unclear how fetal LIF level is regulated. Here we show evidence that maternal LIF signals drive fetal LIF levels via the placenta, thereby promoting neurogenesis in the fetal brain in rats. Chronological changes showed that LIF concentration in fetal sera (FS) and fetal cerebrospinal fluid peaked at gestational day (GD) 15.5, after the peak of maternal LIF at GD14.5. LIF injection into rat dams at GD15.5 increased the level of ACTH in FS and subsequently increased LIF levels in FS and fetal cerebrospinal fluid. The elevation of fetal LIF after LIF injection into dams was inhibited by in utero injection of anti-ACTH antibody into fetuses. Cultured syncytiotrophoblasts, which express the LIF receptor and glycoprotein 130, were induced to secrete ACTH and up-regulate Pomc expression by the addition of LIF. Nucleated red blood cells from fetuses at GD15.5, but not GD13.5 or GD17.5, displayed LIF secretion in response to ACTH. Moreover, injection of LIF into dams at GD13.5 or GD17.5 did not result in elevation of ACTH or LIF in fetuses. The labeling index of 5-bromo-2′-deoxyuridine-positive cells in the ventricular zone of the cerebral neocortex increased 24 h after injection of LIF into dams at GD15.5 but not GD13.5 or GD17.5. These results suggest that in rats maternal LIF induces ACTH from the placenta, which in turn induces fetal nucleated red blood cells to secrete LIF that finally increases neurogenesis in fetuses around GD15.

scholarly journals Smoothened Signal Transduction Is Promoted by G Protein-Coupled Receptor Kinase 2

2006 ◽  
Vol 26 (20) ◽  
pp. 7550-7560 ◽  
Author(s):  
Alison R. Meloni ◽  
Gregory B. Fralish ◽  
Patrick Kelly ◽  
Ali Salahpour ◽  
James K. Chen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Sonic Hedgehog ◽  
Cellular Proliferation ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Positive Role ◽  
Proliferation And Differentiation ◽  
Hedgehog Proteins ◽  
G Protein Coupled

ABSTRACT Deregulation of the Sonic hedgehog pathway has been implicated in an increasing number of human cancers. In this pathway, the seven-transmembrane (7TM) signaling protein Smoothened regulates cellular proliferation and differentiation through activation of the transcription factor Gli. The activity of mammalian Smoothened is controlled by three different hedgehog proteins, Indian, Desert, and Sonic hedgehog, through their interaction with the Smoothened inhibitor Patched. However, the mechanisms of signal transduction from Smoothened are poorly understood. We show that a kinase which regulates signaling by many “conventional” 7TM G-protein-coupled receptors, G protein-coupled receptor kinase 2 (GRK2), participates in Smoothened signaling. Expression of GRK2, but not catalytically inactive GRK2, synergizes with active Smoothened to mediate Gli-dependent transcription. Moreover, knockdown of endogenous GRK2 by short hairpin RNA (shRNA) significantly reduces signaling in response to the Smoothened agonist SAG and also inhibits signaling induced by an oncogenic Smoothened mutant, Smo M2. We find that GRK2 promotes the association between active Smoothened and β-arrestin 2. Indeed, Gli-dependent signaling, mediated by coexpression of Smoothened and GRK2, is diminished by β-arrestin 2 knockdown with shRNA. Together, these data suggest that GRK2 plays a positive role in Smoothened signaling, at least in part, through the promotion of an association between β-arrestin 2 and Smoothened.

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