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primary cilia spinal cord

Tianjiao Xia, Shuaishuai Chu, Yin Cui, Fangxia Xu, Yue Liu, Jia Song, Yue Qian, Xueming Shao, Xiuxiu Li, Xiaoping Gu, Zhengliang Ma
BACKGROUND: Chronic pain is a debilitating threat to human health, and its molecular mechanism remains undefined. Previous studies have illustrated a key role of cAMP response element-binding protein (CREB) in pain regulation; CREB-regulated transcription coactivator 1 (CRTC1) and microRNA212/132 (miR212/132) are also vital in synaptic plasticity. However, little is known about the interaction among these factors in pain condition. We conducted this experiment mainly to determine the crosstalk between CREB, CRTC1, and miR212/132 in vitro...
June 2017: Anesthesia and Analgesia
Laura I Hudish, Domenico F Galati, Andrew M Ravanelli, Chad G Pearson, Peng Huang, Bruce Appel
The transition of dividing neuroepithelial progenitors to differentiated neurons and glia is essential for the formation of a functional nervous system. Sonic hedgehog (Shh) is a mitogen for spinal cord progenitors, but how cells become insensitive to the proliferative effects of Shh is not well understood. Because Shh reception occurs at primary cilia, which are positioned within the apical membrane of neuroepithelial progenitors, we hypothesized that loss of apical characteristics reduces the Shh signaling response, causing cell cycle exit and differentiation...
July 1, 2016: Development
Carmen Cifuentes-Diaz, Stefano Marullo, Stéphane Doly
Prenylated Rab acceptor family, member 2 (PRAF2) is a four transmembrane domain protein of 19 kDa that is highly expressed in particular areas of mammalian brains. PRAF2 is mostly found in the endoplasmic reticulum (ER) of neurons where it plays the role of gatekeeper for the GB1 subunit of the GABAB receptor, preventing its progression in the biosynthetic pathway in the absence of hetero-dimerization with the GB2 subunit. However, PRAF2 can interact with several receptors and immunofluorescence studies indicate that PRAF2 distribution is larger than the ER, suggesting additional biological functions...
November 2016: Brain Structure & Function
Helly Rachel Goez, Ori Scott, Basma Al-Jabri, Matthew Prowse, Wendy Beaudoin, Stacey Hall, Vivek Mehta, Israel Amirav
OBJECTIVES: Given the involvement of cilia in midline neurodevelopment, we set to determine whether children with midline neuroanatomical defects have increased prevalence of ciliary dysfunction, using nasal nitric oxide measurement, a screening test for primary ciliary dyskinesia. STUDY DESIGN: We measured the nasal nitric oxide levels of 26 children ages 6-17, with congenital midline central nervous system defects, who are otherwise healthy. We evaluated the effect of variables including: age, gender, and anomaly (brain, spinal cord, or combined) on our measurements...
October 2015: Pediatric Neurology
Jennifer H Kong, Linlin Yang, Eric Dessaud, Katherine Chuang, Destaye M Moore, Rajat Rohatgi, James Briscoe, Bennett G Novitch
Throughout the developing nervous system, neural stem and progenitor cells give rise to diverse classes of neurons and glia in a spatially and temporally coordinated manner. In the ventral spinal cord, much of this diversity emerges through the morphogen actions of Sonic hedgehog (Shh). Interpretation of the Shh gradient depends on both the amount of ligand and duration of exposure, but the mechanisms permitting prolonged responses to Shh are not well understood. We demonstrate that Notch signaling plays an essential role in this process, enabling neural progenitors to attain sufficiently high levels of Shh pathway activity needed to direct the ventral-most cell fates...
May 26, 2015: Developmental Cell
Mi-Sun Lee, Kyu-Seok Hwang, Hyun-Woo Oh, Kim Ji-Ae, Hyun-Taek Kim, Hyun-Soo Cho, Jeong-Ju Lee, Je Yeong Ko, Jung-Hwa Choi, Yun-Mi Jeong, Kwan-Hee You, Joon Kim, Doo-Sang Park, Ki-Hoan Nam, Shinichi Aizawa, Hiroshi Kiyonari, Go Shioi, Jong-Hoon Park, Weibin Zhou, Nam-Soon Kim, Cheol-Hee Kim
Cilia are microtubule-based structures that project into the extracellular space. Ciliary defects are associated with several human diseases, including polycystic kidney disease, primary ciliary dyskinesia, left-right axis patterning, hydrocephalus and retinal degeneration. However, the genetic and cellular biological control of ciliogenesis remains poorly understood. The IFT46 is one of the highly conserved intraflagellar transport complex B proteins. In zebrafish, ift46 is expressed in various ciliated tissues such as Kupffer׳s vesicle, pronephric ducts, ears and spinal cord...
April 15, 2015: Developmental Biology
Adeline Orts-Del'Immagine, Anne Kastner, Vanessa Tillement, Catherine Tardivel, Jérôme Trouslard, Nicolas Wanaverbecq
The mammalian spinal cord and medulla oblongata harbor unique neurons that remain in contact with the cerebrospinal fluid (CSF-cNs). These neurons were shown recently to express a polycystin member of the TRP channels family (PKD2L1) that potentially acts as a chemo- or mechanoreceptor. Recent studies carried out in young rodents indicate that spinal CSF-cNs express immature neuronal markers that appear to persist even in adult cells. Nevertheless, little is known about the phenotype and morphological properties of medullar CSF-cNs...
2014: PloS One
Katarina Vukojevic, Tanja Janjic, Mirna Saraga-Babic
The aim of this study was to analyze immunohistochemically the relationships between factors involved in processes of cell proliferation (Ki-67), differentiation (Oct-4) and primary cilia formation (α-tubulin) in the two parts of the developing human spinal cord (SC) of different origin in 11 human concepti (developmental weeks 5-10). Proliferation was highest in weeks 7-8 in the dorsal ventricular zones of the cranial (85.5%) and caudal (12.1%) SC. In the ventricular (VZ), intermediate (IZ) and marginal zones (MZ) of the cranial SC, α-tubulin and Oct-4 were moderately to strongly expressed...
May 2014: Acta Histochemica
Gordana Juric-Sekhar, Jonathan Adkins, Dan Doherty, Robert F Hevner
Joubert syndrome (JS) is an autosomal recessive ciliopathy characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability. The brain is malformed, with severe vermian hypoplasia, fourth ventriculomegaly, and "molar tooth" appearance of the cerebral and superior cerebellar peduncles visible as consistent features on neuroimaging. Neuropathological studies, though few, suggest that several other brain and spinal cord structures, such as the dorsal cervicomedullary junction, may also be affected in at least some patients...
May 2012: Acta Neuropathologica
Xiaoxing Ma, Randy Peterson, John Turnbull
BACKGROUND: The primary cilium is a solitary organelle important in cellular signaling, that projects from the cell surface of most growth-arrested or post-mitotic cells including neurons in the central nervous system. We hypothesized that primary cilial dysfunction might play a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), and as a first step, report on the prevalence of primary cilial markers on cultured motor neurons from the lumbar spinal cord of embryonic wildtype (WT) and transgenic G93A SOD1 mice, and on motor neurons in situ in the lumbar spinal cord...
2011: BMC Neuroscience
Saikat Mukhopadhyay, Peter K Jackson
The tubby mouse shows a tripartite syndrome characterized by maturity-onset obesity, blindness and deafness. The causative gene Tub is the founding member of a family of related proteins present throughout the animal and plant kingdoms, each characterized by a signature carboxy-terminal tubby domain. This domain consists of a β barrel enclosing a central α helix and binds selectively to specific membrane phosphoinositides. The vertebrate family of tubby-like proteins (TULPs) includes the founding member TUB and the related TULPs, TULP1 to TULP4...
2011: Genome Biology
Vanessa L Horner, Tamara Caspary
In the embryonic neural tube, multiple signaling pathways work in concert to create functional neuronal circuits in the adult spinal cord. In the ventral neural tube, Sonic hedgehog (Shh) acts as a graded morphogen to specify neurons necessary for movement. In the dorsal neural tube, bone morphogenetic protein (BMP) and Wnt signals cooperate to specify neurons involved in sensation. Several signaling pathways, including Shh, rely on primary cilia in vertebrates. In this study, we used a mouse mutant with abnormal cilia, Arl13b(hnn), to study the relationship between cilia, cell signaling, and neural tube patterning...
July 1, 2011: Developmental Biology
Yesser H Belgacem, Laura N Borodinsky
Evolutionarily conserved hedgehog proteins orchestrate the patterning of embryonic tissues, and dysfunctions in their signaling can lead to tumorigenesis. In vertebrates, Sonic hedgehog (Shh) is essential for nervous system development, but the mechanisms underlying its action remain unclear. Early electrical activity is another developmental cue important for proliferation, migration, and differentiation of neurons. Here we demonstrate the interplay between Shh signaling and Ca(2+) dynamics in the developing spinal cord...
March 15, 2011: Proceedings of the National Academy of Sciences of the United States of America
Nathan E Hellman, Yan Liu, Erin Merkel, Christina Austin, Stephanie Le Corre, David R Beier, Zhaoxia Sun, Neeraj Sharma, Bradley K Yoder, Iain A Drummond
Cilia are essential for normal organ function and developmental patterning, but their role in injury and regeneration responses is unknown. To probe the role of cilia in injury, we analyzed the function of foxj1, a transcriptional regulator of cilia genes, in response to tissue damage and renal cyst formation. Zebrafish foxj1a, but not foxj1b, was rapidly induced in response to epithelial distension and stretch, kidney cyst formation, acute kidney injury by gentamicin, and crush injury in spinal cord cells...
October 26, 2010: Proceedings of the National Academy of Sciences of the United States of America
Julie C Kiefer
On the surface, the Hedgehog (Hh) pathway and primary cilia make strange bedfellows. Hh is a dynamic regulator of a myriad of developmental processes, ranging from spinal cord and limb patterning to lung branching morphogenesis. By contrast, immotile primary cilia were long considered ancestral holdovers with no known function. Considering the disparate perceptions of these two phenomena, the relatively recent discovery that there is a symbiotic-like relationship between Hh and cilia was unexpected. This primer covers the basics of primary cilia and Hh signaling, highlighting variations in ways they are connected across species, and also discusses the evolutionary implications of these findings...
April 2010: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Amir M Ashique, Youngshik Choe, Mattias Karlen, Scott R May, Khanhky Phamluong, Mark J Solloway, Johan Ericson, Andrew S Peterson
Regulatory factor X (Rfx) homologs regulate the transcription of genes necessary for ciliogenesis in invertebrates and vertebrates. Primary cilia are necessary for Hedgehog signaling and regulation of the activity of the transcriptional regulators known as Gli proteins, which are targets of Hedgehog signaling. Here, we describe an Rfx4(L298P) mouse mutant with distinct dorsoventral patterning defects in the ventral spinal cord and telencephalon due to aberrant Sonic hedgehog (Shh) signaling and Gli3 activity...
November 3, 2009: Science Signaling
Ryan X Norman, Hyuk W Ko, Viola Huang, Christine M Eun, Lisa L Abler, Zhen Zhang, Xin Sun, Jonathan T Eggenschwiler
Tubby-like protein 3 (TULP3) is required for proper embryonic development in mice. Disruption of mouse Tulp3 results in morphological defects in the embryonic craniofacial regions, the spinal neural tube and the limbs. Here, we show that TULP3 functions as a novel negative regulator of Sonic hedgehog (Shh) signaling in the mouse. In Tulp3 mutants, ventral cell types in the lumbar neural tube, which acquire their identities in response to Shh signaling, are ectopically specified at the expense of dorsal cell types...
May 15, 2009: Human Molecular Genetics
Pamela V Tran, Courtney J Haycraft, Tatiana Y Besschetnova, Annick Turbe-Doan, Rolf W Stottmann, Bruce J Herron, Allyson L Chesebro, Haiyan Qiu, Paul J Scherz, Jagesh V Shah, Bradley K Yoder, David R Beier
Characterization of previously described intraflagellar transport (IFT) mouse mutants has led to the proposition that normal primary cilia are required for mammalian cells to respond to the sonic hedgehog (SHH) signal. Here we describe an N-ethyl-N-nitrosourea-induced mutant mouse, alien (aln), which has abnormal primary cilia and shows overactivation of the SHH pathway. The aln locus encodes a novel protein, THM1 (tetratricopeptide repeat-containing hedgehog modulator-1), which localizes to cilia. aln-mutant cilia have bulb-like structures at their tips in which IFT proteins (such as IFT88) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants...
April 2008: Nature Genetics
E I Chumasov
This article provides a critical analysis of the concepts of the sensory innervation of the brain and spinal cord presented in Sotnikov's articles in issues 2 and 3 of this volume. Criteria for the identification of intracerebral primary sensory neurons and the possible roles of neuronal cilia are discussed. The significance of asynaptic dendrites and bipolar cells is considered. The importance of the correct use of a variety of terms is emphasized, and the need for using combined morphological and electrophysiological analysis in investigating sensory intracerebral exteroceptors is noted...
June 2006: Neuroscience and Behavioral Physiology
O S Sotnikov
Published data and our own studies on the sensory innervation of the brain are summarized. Primary interoceptive sensory neurons were analyzed: brain neurons bearing cilia; supraependymal plexuses and intraependymal neurons in contact with the cerebrospinal fluid; Cajal-Retzius neurons in the boundary layer of the cerebral cortex; Dolgo-Saburov paravasal neurons in the brain and spinal cord; Lugaro cells in the cerebellum; and various synaptically NO-positive neurons in the cerebral cortex, whose asynaptic dendrites innervate the precapillary space...
June 2006: Neuroscience and Behavioral Physiology
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