Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2.
Development 143(12):2194 (2016)
Delamination of neural crest (NC) cells is a bona fide physiological model of epithelial-to-mesenchymal transition (EMT), a process that is influenced by Wnt/β-catenin signalling. Using two in vivo models, we show that Wnt/β-catenin signalling is transiently inhibited at the time of NC delaminat...
Ciliary adenylyl cyclases control the Hedgehog pathway.
Journal of Cell Science 128(15):2928 (2015)
Protein kinase A (PKA) accumulates at the base of the cilium where it negatively regulates the Hedgehog (Hh) pathway. Although PKA activity is essentially controlled by the cAMP produced by adenylyl cyclases, the influence of these enzymes on the Hh pathway remains unclear. Here, we show that ad...
Sustained Wnt/β-catenin signalling causes neuroepithelial aberrations through the accumulation of aPKC at the apical pole.
Nature Communications 5:4168 (2014)
β-Catenin mediates the canonical Wnt pathway by stimulating Tcf-dependent transcription and also associates to N-cadherin at the apical complex (AC) of neuroblasts. Here, we show that while β-catenin activity is required to form the AC and to maintain the cell polarity, oncogenic mutations that ...
Smad2 and Smad3 cooperate and antagonize simultaneously in vertebrate neurogenesis.
Journal of Cell Science 126(Pt 23):5335 (2013)
The transforming growth factor beta (TGF-β) pathway plays key roles in development and cancer. TGF-β signaling converges on the Smad2 and Smad3 effectors, which can either cooperate or antagonize to regulate their transcriptional targets. Here we performed in vivo and in silico experiments to st...
MicroRNA 22 regulates cell cycle length in cerebellar granular neuron precursors.
Molecular and Cellular Biology 33(14):2706 (2013)
During cerebellum development, Sonic hedgehog (Shh)-induced proliferation of cerebellar granular neuronal precursors (CGNPs) is potently inhibited by bone morphogenetic proteins (BMPs). We have previously reported the upregulation of TIEG-1 and Mash1, two antimitotic factors that modulate MYCN t...
IRS-2 Deficiency impairs NMDA receptor-dependent long-term potentiation.
Cerebral Cortex 22(8):1717 (2012)
The beneficial effects of insulin and insulin-like growth factor I on cognition have been documented in humans and animal models. Conversely, obesity, hyperinsulinemia, and diabetes increase the risk for neurodegenerative disorders including Alzheimer's disease (AD). However, the mechanisms by w...
Sonic Hedgehog-induced proliferation requires specific Gα inhibitory proteins.
Journal of Biological Chemistry 286(10):8067 (2011)
Proliferation of cerebellar granular neuronal precursors (CGNPs) is mediated by Sonic Hedgehog (Shh), which activates the Patched and Smoothened (Smo) receptor complex. Although its protein sequence suggests that Smo is a G protein coupled receptor (GPCR), the evidence that this receptor utilize...
Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base.
Journal of Cell Science 123(Pt 1):62 (2010)
Cerebellar granular neuronal precursors (CGNPs) proliferate in response to the mitogenic activity of Sonic hedgehog (Shh), and this proliferation is negatively regulated by activation of cAMP-dependent protein kinase (PKA). In the basal state, the PKA catalytic subunits (C-PKA) are inactive beca...
Probucol increases glutathione peroxidase-1 activity and displays long-lasting protection against methylmercury toxicity in cerebellar granule cells.
Toxicological Sciences 112(2):416 (2009)
Methylmercury (MeHg) is an environmental neurotoxicant whose molecular mechanisms underlying toxicity remain elusive. Here, we investigated molecular events involved in MeHg-induced neurotoxicity in cultured cerebellar granule cells (CGCs) as well as potential protective strategies for such toxi...
Expression of the proneural gene encoding Mash1 suppresses MYCN mitotic activity.
Journal of Cell Science 122(Pt 5):595 (2009)
Murine Mash1 (Ascl1) is a member of the basic helix-loop-helix family of transcription factors and has been described to promote differentiation in some neural precursors. The process of differentiation is coordinated with a concomitant cell-cycle arrest, but the molecular mechanism of this proc...
Bone morphogenetic protein 2 opposes Shh-mediated proliferation in cerebellar granule cells through a TIEG-1-based regulation of Nmyc.
Journal of Biological Chemistry 282(51):37170 (2007)
Nmyc is a potent regulator of cell cycle in cerebellar granular neuron precursors (CGNPs) and has been proposed to be the main effector of Shh (Sonic hedgehog) proliferative activity. Nmyc ectopic expression is sufficient to promote cell autonomous proliferation and can lead to tumorigenesis. Bo...
Bmp2 antagonizes sonic hedgehog-mediated proliferation of cerebellar granule neurones through Smad5 signalling.
Development 131(13):3159 (2004)
During development of the cerebellum, sonic hedgehog (Shh) is directly responsible for the proliferation of granule cell precursors in the external germinal layer. We have looked for signals able to regulate a switch from the Shh-mediated proliferative response to one that directs differentiatio...
Beta1-integrins are critical for cerebellar granule cell precursor proliferation.
Journal of Neuroscience 24(13):3402 (2004)
We have previously shown that mice with a CNS restricted knock-out of the integrin beta1 subunit gene (Itgb1-CNSko mice) have defects in the formation of lamina and folia in the cerebral and cerebellar cortices that are caused by disruption of the cortical marginal zones. Cortical structures in ...
Insulin-induced up-regulated uncoupling protein-1 expression is mediated by insulin receptor substrate 1 through the phosphatidylinositol 3-kinase/Akt signaling pathway in fetal brown adipocytes.
Journal of Biological Chemistry 278(12):10221 (2003)
To investigate the role of insulin receptor substrate-1 (IRS-1) and its downstream signaling in insulin-induced thermogenic differentiation of brown adipocytes, we have reconstituted IRS-1-deficient fetal brown adipocytes (IRS-1(-/-)) with wild-type IRS-1 (IRS-1(wt)). The lack of IRS-1 resulted ...
Blockade of cannabinoid CB(1) receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity.
Journal of Neurochemistry 82(1):154 (2002)
The ability of cannabinoid CB(1) receptors to influence glutamatergic excitatory neurotransmission has fueled interest in how these receptors and their endogenous ligands may interact in conditions of excitotoxic insults. The present study characterized the impact of stimulated and inhibited CB(...
Interaction of p59fynwith Interferon-Activated Jak Kinases
Biochemical and Biophysical Research Communicat... 235(1):83 (1997)
During IFNα stimulation, p59
fynassociates with the Type I IFNR-associated Tyk-2 kinase in several human hematopoietic cell lines
in vivo.This interaction is direct, and is mediated by the SH2 domain in p59
fyn, as shown by binding studies using glutathione-S-tranferase fu...
Ontogeny of insulin-like growth factor I, its receptor, and its binding proteins in the rat hypothalamus
Developmental Brain Research 62(2):169 (1991)
A role for the insulin-like growth factors (IGFs) in brain growth and differentiation has recently been suggested. In previous studies on fetal hypothalamic cells we found a trophic influence of IGF-I on in vitro survival and differentiation of both neurons and glia. We have now investigate...
Climbing fiber deafferentation reduces insulin-like growth factor I (IGF-I) content in cerebellum
Brain Research 564(2):348 (1991)
The presence of insulin-like grwoth factor (IGF-I) and its mRNA in adult rat cerebellum has recently been documented. Previous immunocytochemical studies showed prominent IGF-I-like staining in fibers around Purkinje cell somas. To determine the origin of this IGF-I input to the Purkinje ce...