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Fgfr3 regulates development of the caudal telencephalon

Randal X. Moldrich, Cecilia Mezzera, William M. Holmes, Sailaja Goda, Sam J. Brookfield, Alastair J. Rankin, Emily Barr, Nyoman Kurniawan, Deborah Dewar, Linda J. Richards, Guillermina López-Bendito, Tomoko Iwata
2011 Developmental Dynamics  
MOLDRICH ET AL. MOLDRICH ET AL. MOLDRICH ET AL.  ...  TrackVis.org, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA) according to high angular resolution diffusion (HARDI) and Q-ball models (Moldrich et al. 2010; Tuch,  ... 
doi:10.1002/dvdy.22636 pmid:21491541 fatcat:ab6muvqcsfh2fanwkzp2nqsrhy

Nuclear factor I gene expression in the developing forebrain

Céline Plachez, Charlotta Lindwall, Nana Sunn, Michael Piper, Randal X. Moldrich, Christine E. Campbell, Jason M. Osinski, Richard M. Gronostajski, Linda J. Richards
2008 Journal of Comparative Neurology  
For the Western blot analysis we used JEG-3 choriocarcinoma cells transfected with vectors expressing HA-tagged NFIA, NFIB, NFI-C, or NFI-X (Chaudhry et al., 1997) .  ...  Immunocytochemistry on fixed, cultured cells was performed by first blocking and permeabilizing the cells in 1ϫ PBS containing 2% normal goat serum and 0.5% Triton X-100.  ... 
doi:10.1002/cne.21645 pmid:18335562 fatcat:5ly4qgivajftjhwedvydpnjsru

Nuclear factor I gene expression in the developing forebrain

Céline Plachez, Charlotta Lindwall, Nana Sunn, Michael Piper, Randal X. Moldrich, Christine E. Campbell, Jason M. Osinski, Richard M. Gronostajski, Linda J. Richards
2008 Journal of Comparative Neurology  
For the Western blot analysis we used JEG-3 choriocarcinoma cells transfected with vectors expressing HA-tagged NFIA, NFIB, NFI-C, or NFI-X (Chaudhry et al., 1997) .  ...  Immunocytochemistry on fixed, cultured cells was performed by first blocking and permeabilizing the cells in 1ϫ PBS containing 2% normal goat serum and 0.5% Triton X-100.  ... 
doi:10.1002/cne.21724 fatcat:nbwkomtsu5df7kbfh3eqv2m5fe

Nuclear factor I gene expression in the developing forebrain

Céline Plachez, Charlotta Lindwall, Nana Sunn, Michael Piper, Randal X. Moldrich, Christine E. Campbell, Jason M. Osinski, Richard M. Gronostajski, Linda J. Richards
2008 Journal of Comparative Neurology  
For the Western blot analysis we used JEG-3 choriocarcinoma cells transfected with vectors expressing HA-tagged NFIA, NFIB, NFI-C, or NFI-X (Chaudhry et al., 1997) .  ...  Immunocytochemistry on fixed, cultured cells was performed by first blocking and permeabilizing the cells in 1ϫ PBS containing 2% normal goat serum and 0.5% Triton X-100.  ... 
doi:10.1002/cne.21722 fatcat:6fksctd6nfdi7ansodll57xhwi

Multiple non-cell-autonomous defects underlie neocortical callosal dysgenesis in Nfib-deficient mice

Michael Piper, Randal X Moldrich, Charlotta Lindwall, Erica Little, Guy Barry, Sharon Mason, Nana Sunn, Nyoman Kurniawan, Richard M Gronostajski, Linda J Richards
2009 Neural Development  
Agenesis of the corpus callosum is associated with many human developmental syndromes. Key mechanisms regulating callosal formation include the guidance of axons arising from pioneering neurons in the cingulate cortex and the development of cortical midline glial populations, but their molecular regulation remains poorly characterised. Recent data have shown that mice lacking the transcription factor Nfib exhibit callosal agenesis, yet neocortical callosal neurons express only low levels of
more » ... . Therefore, we investigate here how Nfib functions to regulate non-cell-autonomous mechanisms of callosal formation. Results: Our investigations confirmed a reduction in glial cells at the midline in Nfib -/mice. To determine how this occurs, we examined radial progenitors at the cortical midline and found that they were specified correctly in Nfib mutant mice, but did not differentiate into mature glia. Cellular proliferation and apoptosis occurred normally at the midline of Nfib mutant mice, indicating that the decrease in midline glia observed was due to deficits in differentiation rather than proliferation or apoptosis. Next we investigated the development of callosal pioneering axons in Nfib -/mice. Using retrograde tracer labelling, we found that Nfib is expressed in cingulate neurons and hence may regulate their development. In Nfib -/mice, neuropilin 1-positive axons fail to cross the midline and expression of neuropilin 1 is diminished. Tract tracing and immunohistochemistry further revealed that, in late gestation, a minor population of neocortical axons does cross the midline in Nfib mutants on a C57Bl/6J background, forming a rudimentary corpus callosum. Finally, the development of other forebrain commissures in Nfib-deficient mice is also aberrant. Conclusion: The formation of the corpus callosum is severely delayed in the absence of Nfib, despite Nfib not being highly expressed in neocortical callosal neurons. Our results indicate that in addition to regulating the development of midline glial populations, Nfib also regulates the expression of neuropilin 1 within the cingulate cortex. Collectively, these data indicate that defects in midline glia and cingulate cortex neurons are associated with the callosal dysgenesis seen in Nfib-deficient mice, and provide insight into how the development of these cellular populations is controlled at a molecular level.
doi:10.1186/1749-8104-4-43 pmid:19961580 pmcid:PMC2802587 fatcat:byexzp7d5neupkflwmw3v4336m

Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder

Laura R Fenlon, Sha Liu, Ilan Gobius, Nyoman D Kurniawan, Skyle Murphy, Randal X Moldrich, Linda J Richards
2015 Neural Development  
After 3 × 20-min washes with PBS, the sections were incubated with the secondary antibody diluted in 0.2% v/v Triton-X 100 in PBS for 1 h.  ...  in 0.9% v/v hydrogen peroxide in blocking solution: 2% v/v normal goat serum (Vector Laboratories, Burlingame, USA) or normal donkey serum (Jackson Laboratories, Bar Harbor, USA) and 0.2% v/v Triton-X  ... 
doi:10.1186/s13064-015-0033-y pmid:25879444 pmcid:PMC4412039 fatcat:t3tbezlyrjhwdjmm5t64262dle

Multiple Slits regulate the development of midline glial populations and the corpus callosum

Divya K. Unni, Michael Piper, Randal X. Moldrich, Ilan Gobius, Sha Liu, Thomas Fothergill, Amber-Lee S. Donahoo, John M. Baisden, Helen M. Cooper, Linda J. Richards
2012 Developmental Biology  
The Slit molecules are chemorepulsive ligands that regulate axon guidance at the midline of both vertebrates and invertebrates. In mammals, there are three Slit genes, but only Slit2 has been studied in any detail with regard to mammalian brain commissure formation. Here, we sought to understand the relative contributions that Slit proteins make to the formation of the largest brain commissure, the corpus callosum. Slit ligands bind Robo receptors, and previous studies have shown that Robo1 −/−
more » ... mice have defects in corpus callosum development. However, whether the Slit genes signal exclusively through Robo1 during callosal formation is unclear. To investigate this, we compared the development of the corpus callosum in both Slit2 −/− and Robo1 −/− mice using diffusion magnetic resonance imaging. This analysis demonstrated similarities in the phenotypes of these mice, but crucially also highlighted subtle differences, particularly with regard to the guidance of post-crossing axons. Analysis of single mutations in Slit family members revealed corpus callosum defects (but not complete agenesis) in 100% of Slit2 −/− mice and 30% of Slit3 −/− mice, whereas 100% of Slit1 −/− ; Slit2 −/− mice displayed complete agenesis of the corpus callosum. These results revealed a role for Slit1 in corpus callosum development, and demonstrated that Slit2 was necessary but not sufficient for midline crossing in vivo. However, co-culture experiments utilising Robo1 −/− tissue versus Slit2 expressing cell blocks demonstrated that Slit2 was sufficient for the guidance activity mediated by Robo1 in pre-crossing neocortical axons. This suggested that Slit1 and Slit3 might also be involved in regulating other mechanisms that allow the corpus callosum to form, such as the establishment of midline glial populations. Investigation of this revealed defects in the development and dorso-ventral positioning of the indusium griseum glia in multiple Slit mutants. These findings indicate that Slits regulate callosal development via both classical chemorepulsive mechanisms, and via a novel role in mediating the correct positioning of midline glial populations. Finally, our data also indicate that some of the roles of Slit proteins at the midline may be independent of Robo signalling, suggestive of additional receptors regulating Slit signalling during development. The corpus callosum is the largest axon tract in the brain, yet the molecular mechanisms regulating its formation remain poorly understood. The corpus callosum is made up of axons from neurons predominantly located in layers II, III and V of the neocortex. These neurons extend axons across the cortical midline via the corpus callosum and into the contralateral hemisphere, where they form homotopic connections (Wise and Jones, 1976) . In humans, the rostral (rostrum and genu) and middle (body) regions of the corpus callosum develop embryonically, whereas the caudal (splenium) corpus callosum develops largely during the perinatal period through to adolescence (Paul et al., 2007) . In mice, formation of the corpus callosum is initiated at approximately embryonic day 16 (E16) and concludes around postnatal day 15 (P15; Ozaki and Wahlsten, 1992; Richards, 2002) . The environment through which callosal axons navigate during the formation of the corpus callosum is complex, with a number of different axonal guidance families implicated in regulating their guidance, including members of the Slit, Semaphorin, Wnt, and Ephrin families, as well as Draxin (Bagri et al.
doi:10.1016/j.ydbio.2012.02.004 pmid:22349628 fatcat:tlm53ijmy5dh7mikcq2dgtqkt4

Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development

Julien Laffaire, Isabelle Rivals, Luce Dauphinot, Fabien Pasteau, Rosine Wehrle, Benoit Larrat, Tania Vitalis, Randal X Moldrich, Jean Rossier, Ralph Sinkus, Yann Herault, Isabelle Dusart (+1 others)
2009 BMC Genomics  
Julien Laffaire, Isabelle Rivals, Luce Dauphinot, Fabien Pasteau, Rosine Wehrle, Benoît Larrat, Tania Vitalis, Randal X Moldrich, Jean Rossier, Ralph Sinkus, et al.  ...  Genes are ordered on the x axis according to their expression ratio.  ... 
doi:10.1186/1471-2164-10-138 pmid:19331679 pmcid:PMC2678156 fatcat:fibhw6urxvgnlhknpfqvmiikhq

Clathrin-dependent APP endocytosis and Aβ secretion are highly sensitive to the level of plasma membrane cholesterol

Jack-Christophe Cossec, Anne Simon, Catherine Marquer, Randal X. Moldrich, Christophe Leterrier, Jean Rossier, Charles Duyckaerts, Zsolt Lenkei, Marie-Claude Potier
2010 Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids  
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
doi:10.1016/j.bbalip.2010.05.010 pmid:20580937 fatcat:q5ghutwy6rai7iutkoai74bt4a

Inactivation of Anandamide Signaling: A Continuing Debate

Hesham Khairy, Wael E. Houssen
2010 Pharmaceuticals  
Wenger, T.; Moldrich, G. The role of endocannabinoids in the hypothalamic regulation of visceral function. Prostaglandins Leukot. Essent. Fatty Acids 2002, 66, 301307. 33. Randall, M.  ...  Tian, X.; Guo, J.; Yao, F.; Yang D. P.; Makriyannis A. The conformation, location, and dynamic properties of the endocannabinoid ligand anandamide in a membrane bilayer. J. Biol.  ... 
doi:10.3390/ph3113355 fatcat:ilfoqa2uozajhnlu3omn4tpxpa

Homodimerization of Amyloid Precursor Protein at the Plasma Membrane: A homoFRET Study by Time-Resolved Fluorescence Anisotropy Imaging

Viviane Devauges, Catherine Marquer, Sandrine Lécart, Jack-Christophe Cossec, Marie-Claude Potier, Emmanuel Fort, Klaus Suhling, Sandrine Lévêque-Fort, Andrew Francis Hill
2012 PLoS ONE  
Acknowledgments The authors thank Randal X Moldrich (The Queensland Brain Institute, St. Lucia, Australia) for the APP-eGFP constructs. The authors also thank James A.  ...  We found x NA to be 1.2 (Fig.  ...  Since the NA of the objective 106 is 0.3, x NA equalled 2.  ... 
doi:10.1371/journal.pone.0044434 pmid:22973448 pmcid:PMC3433432 fatcat:e6j34ghuhndcnimnwcn6nuctmm

Mechanism-based approaches to treating fragile X

Gül Dölen, Randall L. Carpenter, Timothy D. Ocain, Mark F. Bear
2010 Pharmacology and Therapeutics  
a r t i c l e i n f o Keywords: Fragile X Metabotropic glutamate receptor (mGluR) Plasticity Autism Long-term depression (LTD) Fragile X mental retardation protein (FMRP) Fragile X is the leading inherited  ...  Although it remains to be seen if mGluR5 antagonists or related approaches will succeed in humans with fragile X, the progress in fragile X stands as a strong testament to the power of applying knowledge  ...  term=fragile+X&rank=7).  ... 
doi:10.1016/j.pharmthera.2010.02.008 pmid:20303363 fatcat:dtftnfpjqzaz3j7ra4xcmtc7zu

Wiring the Brain: The Biology of Neuronal Guidance

A. Chedotal, L. J. Richards
2010 Cold Spring Harbor Perspectives in Biology  
Images in C-E courtesy of Dr Nyoman Kurniawan and Dr Randal Moldrich (The University of Queensland). Scale bar in E ¼ 400 mm in A, 80 mm in B, 2 mm in C and E and 1.35 mm in D.  ...  Abbreviations: IV, trochlear nucleus; V, trigeminal nucleus; VI, abducens nucleus; VII, facial nucleus; IX, glossopharyngeal nucleus; X, vagus nucleus; XII, hypoglossus nucleus; MHB midbrain hindbrain  ... 
doi:10.1101/cshperspect.a001917 pmid:20463002 pmcid:PMC2869517 fatcat:ovk33qifynfcjlya6cybrmv7au

Prenatal pharmacotherapy rescues brain development in a Down's syndrome mouse model

Sandra Guidi, Fiorenza Stagni, Patrizia Bianchi, Elisabetta Ciani, Andrea Giacomini, Marianna De Franceschi, Randal Moldrich, Nyoman Kurniawan, Karine Mardon, Alessandro Giuliani, Laura Calzà, Renata Bartesaghi
2013 Brain  
., 1995) were obtained from Jackson Laboratories and maintained on the original genetic background by mating them with C57BL/6JEi x C3SnHeSnJ (B6EiC3) F1 males.  ...  Experimental protocol Ts65Dn females (n = 29) were bred with C57BL/6JEi x C3SnHeSnJ (B6EiC3) F1 males (n = 29). Conception was determined by examining the vaginal plug.  ... 
doi:10.1093/brain/awt340 pmid:24334313 fatcat:2ywct7udq5fc5pkeotn7k4gf44

The Endocannabinoid Antagonist AM251 as a Method of Protection Prior to Global Cerebral Ischemia: Implications for Dopamine Function, Neuronal Survival and Behaviour

Megan Dunbar, Université D'Ottawa / University Of Ottawa, Université D'Ottawa / University Of Ottawa
2013
The test consisted of an X shaped plexiglass structure, all four arms measured 50cm x 10cm, the open arm had a 5mm plexiglass lip and the closed arm had 40 cm walls.  ...  Rats treated with AM251 had significantly reduced lever pressing, similar results were seen with rats given a direct dopamine antagonist (Randall et al, 2012) .  ... 
doi:10.20381/ruor-3115 fatcat:r7o4qpncqjevfmrtfw22hvmwsy
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