Specific regulation of cyclins D1 and D2 by FGF and Shh signaling coordinates cell cycle progression, patterning, and differentiation during early steps of spinal cord development

Lobjois, Valérie; Bénazéraf, Bertrand; Bertrand, Nicolas; Médevielle, François; Pituello, Fabienne

doi:10.1016/j.ydbio.2004.05.031

Cited by 85 publications

(86 citation statements)

References 53 publications

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“…Our findings that the Hh pathway is activated in acute lymphoblastic leukemia cells broadens the growing list of Hh-associated cancers. Although the mechanism underlying Hh-mediated tumorigenesis is poorly understood, several studies indicate a role for Hh as a regulator of the cell cycle machinery (23,(43)(44)(45)(46). These studies are in agreement with our observations that inhibition of Hh pathway by a SMO inhibitor KAAD-cyclopamine leads to cell cycle arrest in G 1 /S, whereas a structurally related analog, tomatidine, shows no effect on the cell cycle progression.…”

Section: Discussionsupporting

confidence: 92%

Protein Kinase A, not Epac, Suppresses Hedgehog Activity and Regulates Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia Cells

Mei

Johnson

et al. 2007

Journal of Biological Chemistry

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Cyclic AMP synergizes strongly with glucocorticoids (GC) to induce apoptosis in normal or malignant lymphoid cells. We examined the individual roles that cAMP-dependent protein kinase (PKA) and Epac (exchange protein directly activated by cAMP), two intracellular cAMP receptors, play in this synergistic effect. Our studies demonstrate that PKA is responsible for the observed synergism with GC, whereas Epac exerts a weak antagonistic effect against GC-induced apoptosis. We find that endogenous PKA activity is higher in the GC-sensitive clone than in the GC-resistant clone. In the GC-sensitive clone, higher PKA activity is associated with lower Hedgehog (Hh) activity. Moreover, inhibition of Hh activity by Hh pathway-specific inhibitors leads to cell cycle arrest and apoptosis in CEM (human acute lymphoblastic leukemia, T lineage) cells, and the GC-sensitive clone is more sensitive to Hh inhibition. These results suggest that Hh activity is critical for leukemia cell growth and survival and that the level of Hh activity is in part responsible for the synergism between cAMP and GC.

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Section: Discussionsupporting

confidence: 92%

Protein Kinase A, not Epac, Suppresses Hedgehog Activity and Regulates Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia Cells

Mei

Johnson

et al. 2007

Journal of Biological Chemistry

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“…Their occurrence coincides with the onset of altered Shh signaling at E10.5 (Ueta et al, 2008) and the regionalization and growth defects in the Pdn/Pdn ventral telencephalon are consistent with known roles of Shh in regulating ventral telencephalic gene expression (Shimamura and Rubenstein, 1997;Rallu et al, 2002;Fuccillo et al, 2004;Xu et al, 2005;Yu et al, 2009b) and the expression of cell cycle regulators in neural tissues (Kenney and Rowitch, 2000;Ishibashi and McMahon, 2002;Kenney et al, 2003;Oliver et al, 2003;Lobjois et al, 2004;Cayuso et al, 2006;Alvarez-Medina et al, 2009). Also, ectopic Shh expression in the dorsal spinal cord results in reduced neurogenesis (Rowitch et al, 1999).…”

Section: Discussionsupporting

confidence: 76%

TheGli3Hypomorphic MutationPdnCauses Selective Impairment in the Growth, Patterning, and Axon Guidance Capability of the Lateral Ganglionic Eminence

Magnani¹,

Hasenpusch‐Theil²,

Jacobs³

et al. 2010

J. Neurosci.

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Previous studies have defined a requirement for Sonic hedgehog (Shh) signaling in patterning the ventral telencephalon, a major source of the neuronal diversity found in the mature telencephalon. The zinc finger transcription factor Gli3 is a critical component of the Shh signaling pathway and its loss causes major defects in telencephalic development. Gli3 is expressed in a graded manner along the dorsoventral axis of the telencephalon but it is unknown whether Gli3 expression levels are important for dorsoventral telencephalic patterning. To address this, we used the Gli3 hypomorphic mouse mutant Polydactyly Nagoya (Pdn). We show that in Pdn/Pdn embryos, the telencephalic expression of Gli3 remains graded, but Gli3 mRNA and protein levels are reduced, resulting in an upregulation of Shh expression and signaling. These changes mainly affect the development of the lateral ganglionic eminence (LGE), with some disorganization of the medial ganglionic eminence mantle zone. The pallial/subpallial boundary is shifted dorsally and the production of postmitotic neurons is reduced. Moreover, LGE pioneer neurons that guide corticofugal axons into the LGE do not form properly, delaying the entry of corticofugal axons into the ventral telencephalon. Pdn/Pdn mutants also show severe pathfinding defects of thalamocortical axons in the ventral telencephalon. Transplantation experiments demonstrate that the intrinsic ability of the Pdn ventral telencephalon to guide thalamocortical axons is compromised. We conclude that correct Gli3 levels are particularly important for the LGE's growth, patterning, and development of axon guidance capabilities.

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“…20,25 In addition, consistent with its proliferative activity, FGF signalling maintains Cyclin D2 expression in the caudal neural plate. 26 How FGF signaling inhibits the expression of genes involved in DV patterning of the neural tube is not clear. It is notable however, that in the cerebellum, FGF signalling inhibits Shh signalling.…”

Section: Fgf Signaling and The Establishment Of Spinal Cord Progenitorsmentioning

confidence: 99%

Morphogens and the Control of Cell Proliferation and Patterning in the Spinal Cord

Ulloa¹,

Briscoe²

2007

Cell Cycle

180

137

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The development of animal embryos depends on accurate coordination of the growth and specification of precursor cells. Morphogens, extracellular signals that act at a distance to control cell fate, are crucial in the patterning of embryonic tissues. One of the most extensively studied examples of a morphogen patterned tissue is the developing vertebrate spinal cord. The distribution of distinct neuronal subtypes along the dorsoventral (DV) axis of the spinal cord is determined by counteracting gradients of long-range signals. Wnt and BMP signals promote dorsal identities, while Shh signaling induces ventral identities. Simultaneous to their specification, neural progenitors proliferate, facilitating the growth of the neural tube. In this review we discuss evidence indicating that the signals governing progenitor specification also control proliferation and survival of progenitor cells. Moreover, evidence of reciprocal transcriptional interactions and cross-talk between the signaling pathways has emerged from recent studies. Together these studies suggest ways in which patterning and growth may be coordinated in the spinal cord. One level of interaction is an inhibitory regulation of repressor forms of the transcription factor Gli3-generated in the absence of Shh-on b-catenin activity, the transcription factor activated by Wnt signaling. This interaction may also be relevant in other tissues and situations in which the two signaling pathways are known to participate.

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Specific regulation of cyclins D1 and D2 by FGF and Shh signaling coordinates cell cycle progression, patterning, and differentiation during early steps of spinal cord development

Cited by 85 publications

References 53 publications

Protein Kinase A, not Epac, Suppresses Hedgehog Activity and Regulates Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia Cells

Protein Kinase A, not Epac, Suppresses Hedgehog Activity and Regulates Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia Cells

TheGli3Hypomorphic MutationPdnCauses Selective Impairment in the Growth, Patterning, and Axon Guidance Capability of the Lateral Ganglionic Eminence

Morphogens and the Control of Cell Proliferation and Patterning in the Spinal Cord

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