Distinct and cooperative roles for Nodal and Hedgehog signals during hypothalamic development

Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3055-3065 ◽  
Author(s):  
Juliette Mathieu ◽  
Anukampa Barth ◽  
Frederic M. Rosa ◽  
Stephen W. Wilson ◽  
Nadine Peyriéras
Keyword(s):  
Signaling Pathways ◽  
Hedgehog Signaling ◽  
Evolutionary Conservation ◽  
Neural Plate ◽  
Nodal Signaling ◽  
Functional Importance ◽  
Anterior Dorsal ◽  
Site Of Action ◽  
Prechordal Plate ◽  
Further Development

Despite its evolutionary conservation and functional importance, little is known of the signaling pathways that underlie development of the hypothalamus. Although mutations affecting Nodal and Hedgehog signaling disrupt hypothalamic development, the time and site of action and the exact roles of these pathways remain very poorly understood. Unexpectedly, we show here that cell-autonomous reception of Nodal signals is neither required for the migration of hypothalamic precursors within the neural plate, nor for further development of the anterior-dorsal hypothalamus. Nodal signaling is, however, cell-autonomously required for establishment of the posterior-ventral hypothalamus. Conversely, Hedgehog signaling antagonizes the development of posterior-ventral hypothalamus, while promoting anterior-dorsal hypothalamic fates. Besides their distinct roles in the regionalization of the diencephalon, we reveal cooperation between Nodal and Hedgehog pathways in the maintenance of the anterior-dorsal hypothalamus. Finally we show that it is the prechordal plate and not the head endoderm that provides the early signals essential for establishment of the hypothalamus.

scholarly journals Ancient Origins and Evolutionary Conservation of Intracellular and Neural Signaling Pathways Engaged by the Leptin Receptor

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4202-4214 ◽  
Author(s):  
Melissa Y. Cui ◽  
Caroline K. Hu ◽  
Chris Pelletier ◽  
Adam Dziuba ◽  
Rose H. Slupski ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Leptin Receptor ◽  
Evolutionary Conservation ◽  
Neural Signaling

scholarly journals Trafficking to the primary cilium membrane

2017 ◽  
Vol 28 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Saikat Mukhopadhyay ◽  
Hemant B. Badgandi ◽  
Sun-hee Hwang ◽  
Bandarigoda Somatilaka ◽  
Issei S. Shimada ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Signaling Pathways ◽  
Primary Cilium ◽  
Hedgehog Signaling ◽  
Diffusion Barriers ◽  
Disease Pathogenesis ◽  
Ciliary Membrane ◽  
Multiple Organs ◽  
Sensory Reception

The primary cilium has been found to be associated with a number of cellular signaling pathways, such as vertebrate hedgehog signaling, and implicated in the pathogenesis of diseases affecting multiple organs, including the neural tube, kidney, and brain. The primary cilium is the site where a subset of the cell's membrane proteins is enriched. However, pathways that target and concentrate membrane proteins in cilia are not well understood. Processes determining the level of proteins in the ciliary membrane include entry into the compartment, removal, and retention by diffusion barriers such as the transition zone. Proteins that are concentrated in the ciliary membrane are also localized to other cellular sites. Thus it is critical to determine the particular role for ciliary compartmentalization in sensory reception and signaling pathways. Here we provide a brief overview of our current understanding of compartmentalization of proteins in the ciliary membrane and the dynamics of trafficking into and out of the cilium. We also discuss major unanswered questions regarding the role that defects in ciliary compartmentalization might play in disease pathogenesis. Understanding the trafficking mechanisms that underlie the role of ciliary compartmentalization in signaling might provide unique approaches for intervention in progressive ciliopathies.

Associations of Kras and Hedgehog signaling pathways and their role in pancreatic cancer

Pancreatology ◽  
2014 ◽  
Vol 14 (3) ◽  
pp. S68
Author(s):  
Beatrice Mohelnikova-Duchonova ◽  
Veronika Brynychova ◽  
Ivana Ihnatova ◽  
Martin Oliverius ◽  
Jan Hlavsa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathways ◽  
Hedgehog Signaling

Inductive interactions direct early regionalization of the mouse forebrain

Development ◽  
1997 ◽  
Vol 124 (14) ◽  
pp. 2709-2718 ◽  
Author(s):  
K. Shimamura ◽  
J.L. Rubenstein
Keyword(s):  
Sonic Hedgehog ◽  
Bone Morphogenetic Proteins ◽  
Molecular Mechanisms ◽  
Neural Plate ◽  
Gene Encoding ◽  
Prechordal Plate ◽  
Optic Vesicles ◽  
The Central Nervous System ◽  
Anterior Neural Plate ◽  
Anterior Posterior

The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in neural plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic neural plate. Molecular properties of the medial neural plate are regulated by the prechordal plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral neural plate is regulated by non-neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior neural ridge regulates patterning of the anterior neural plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral neural plate derivatives. Furthermore, we provide evidence that the neural plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal plate, Sonic Hedgehog, the anterior neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the neural plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define the regional organization.

scholarly journals In Vivo Study on the Effects of Xiaoaiping on the Stemness of Hepatocellular Carcinoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Zhan ◽  
Liang-liang Shi ◽  
Yan Wang ◽  
Bai Wei ◽  
Sheng-li Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Nude Mice ◽  
Tumor Size ◽  
Hedgehog Signaling ◽  
Saline Control ◽  
Intragastric Administration ◽  
Antitumor Effects ◽  
Hcc Cells

Aims.The aim of this study was to examine the effects of Xiaoaiping on the stemness of hepatocellular carcinoma (HCC) cellsin vivoand to investigate the underlying molecular mechanism.Methods.A subcutaneous xenograft nude mouse model was established using Hep3B-derived HCC cells. The mice were randomly assigned to the 100 mg/kg Xiaoaiping or 100μL/20 g normal saline (control) groups (n =3/sex/group) for daily intragastric administration for 14 days. The tumor size was closely monitored during the dosing phase. After the treatment period, the tumor tissues were weighed and harvested for mRNA and protein isolation. qPCR and Western blotting were used to evaluate the expression of cancer stemness markers (epithelial cell adhesion molecule [EpCAM], cluster of differentiation [CD13], CD90, aldehyde dehydrogenase 1 [ALDH1], CD44, and CD45), totipotency factors (sex determining region Y-box 2 [Sox2], Nanog, and octamer-binding transcription factor 4 [Oct4]), and genes involved in the Notch, Wnt/β-catenin, Hedgehog, and Hippo signaling pathways.Key Findings.The tumor size and weight were significantly reduced in the nude mice treated with 100 mg/kg Xiaoaiping when compared with the controls. The Xiaoaiping effects on the stemness markers and totipotency factors included decreased expression of EpCAM, CD24, CD47, Sox2, Oct4, and sal-like protein 4 (SALL4), as well as increased expression of CD13 and ALDH1. In addition, Xiaoaiping inhibited the Hippo, Wnt, and Hedgehog signaling pathways.Conclusion.Xiaoaiping significantly inhibited the growth of HCC xenograft in nude mice. These antitumor effects may be mediated by modulating the expression of multiple stemness markers and totipotency factors and inhibition of the Hippo, Wnt, and Hedgehog signaling pathways.

scholarly journals Wingless and Hedgehog signaling pathways regulate orthodenticle and eyes absent during ocelli development in Drosophila

2009 ◽  
Vol 329 (1) ◽  
pp. 104-115 ◽  
Author(s):  
Jorge Blanco ◽  
Makiko Seimiya ◽  
Tobias Pauli ◽  
Heinrich Reichert ◽  
Walter J. Gehring
Keyword(s):  
Signaling Pathways ◽  
Hedgehog Signaling ◽  
Eyes Absent

Discovery of Inhibitors of the Wnt and Hedgehog Signaling Pathways through the Catalytic Enantioselective Synthesis of an Iridoid-Inspired Compound Collection

2013 ◽  
Vol 125 (47) ◽  
pp. 12630-12634 ◽  
Author(s):  
Hiroshi Takayama ◽  
Zhi-Jun Jia ◽  
Lea Kremer ◽  
Jonathan O. Bauer ◽  
Carsten Strohmann ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Hedgehog Signaling ◽  
Enantioselective Synthesis ◽  
Compound Collection

scholarly journals The Roles of Hedgehog Signaling in Upper Lip Formation

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Hiroshi Kurosaka
Keyword(s):  
Signaling Pathways ◽  
Hedgehog Signaling ◽  
Cleft Lip ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Craniofacial Abnormalities ◽  
Facial Growth ◽  
Congenital Diseases ◽  
Orofacial Clefting ◽  
Facial Development

Craniofacial development consists of a highly complex sequence of the orchestrated growth and fusion of facial processes. It is also known that craniofacial abnormalities can be detected in 1/3 of all patients with congenital diseases. Within the various craniofacial abnormalities, orofacial clefting is one of the most common phenotypic outcomes associated with retarded facial growth or fusion. Cleft lip is one of the representative and frequently encountered conditions in the spectrum of orofacial clefting. Despite various mechanisms or signaling pathways that have been proposed to be the cause of cleft lip, a detailed mechanism that bridges individual signaling pathways to the cleft lip is still elusive.Shhsignaling is indispensable for normal embryonic development, and disruption can result in a wide spectrum of craniofacial disorders, including cleft lip. This review focuses on the current knowledge about the mechanisms of facial development and the etiology of cleft lip that are related toShhsignaling.

scholarly journals Zebrafish Dkk1, induced by the pre-MBT Wnt signaling, is secreted from the prechordal plate and patterns the anterior neural plate

2000 ◽  
Vol 98 (1-2) ◽  
pp. 3-17 ◽  
Author(s):  
Minori Shinya ◽  
Cathrin Eschbach ◽  
Matthew Clark ◽  
Hans Lehrach ◽  
Makoto Furutani-Seiki
Keyword(s):  
Wnt Signaling ◽  
Neural Plate ◽  
Prechordal Plate ◽  
Anterior Neural Plate

scholarly journals Mutations in BMP4 Cause Eye, Brain, and Digit Developmental Anomalies: Overlap between the BMP4 and Hedgehog Signaling Pathways

2008 ◽  
Vol 82 (2) ◽  
pp. 304-319 ◽  
Author(s):  
Preeti Bakrania ◽  
Maria Efthymiou ◽  
Johannes C. Klein ◽  
Alison Salt ◽  
David J. Bunyan ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Hedgehog Signaling ◽  
Developmental Anomalies
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