Intrastriatal sonic hedgehog injection increases Patched transcript levels in the adult rat subventricular zone

Charytoniuk, Dorota; Traiffort, Élisabeth; Hantraye, P.; Hermel, Jean‐Michel; Galdes, Alphonse; Ruat, Martial

doi:10.1046/j.1460-9568.2002.02412.x

Cited by 41 publications

(37 citation statements)

References 34 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…phenotype of conditional Shh signaling mutants (Machold et al, 2003) and with the increase in Ptch1 expression observed after injection of Shh into the striatum (Charytoniuk et al, 2002). However, we further show that in vitro addition of Shh results in an increase in SVZ cell proliferation and in the number of cells with stem cell properties and resulting neurons, while blocking its function decreases their number.…”

Section: Introductionmentioning

confidence: 47%

Sonic hedgehog controls stem cell behavior in the postnatal and adult brain

Palma¹,

Lim

Dahmane³

et al. 2005

Development

551

437

View full text Add to dashboard Cite

Sonic hedgehog (Shh) signaling controls many aspects of ontogeny, orchestrating congruent growth and patterning. During brain development, Shh regulates early ventral patterning while later on it is critical for the regulation of precursor proliferation in the dorsal brain, namely in the neocortex, tectum and cerebellum. We have recently shown that Shh also controls the behavior of cells with stem cell properties in the mouse embryonic neocortex, and additional studies have implicated it in the control of cell proliferation in the adult ventral forebrain and in the hippocampus. However, it remains unclear whether it regulates adult stem cell lineages in an equivalent manner. Similarly, it is not known which cells respond to Shh signaling in stem cell niches. Here we demonstrate that Shh is required for cell proliferation in the mouse forebrain's subventricular zone (SVZ) stem cell niche and for the production of new olfactory interneurons in vivo. We identify two populations of Gli1+ Shh signaling responding cells: GFAP+ SVZ stem cells and GFAP- precursors. Consistently, we show that Shh regulates the self-renewal of neurosphere-forming stem cells and that it modulates proliferation of SVZ lineages by acting as a mitogen in cooperation with epidermal growth factor (EGF). Together, our data demonstrate a critical and conserved role of Shh signaling in the regulation of stem cell lineages in the adult mammalian brain, highlight the subventricular stem cell astrocytes and their more abundant derived precursors as in vivo targets of Shh signaling, and demonstrate the requirement for Shh signaling in postnatal and adult neurogenesis

show abstract

Section: Introductionmentioning

confidence: 47%

Sonic hedgehog controls stem cell behavior in the postnatal and adult brain

Palma¹,

Lim

Dahmane³

et al. 2005

Development

551

437

View full text Add to dashboard Cite

show abstract

“…2,3,7,9,12,20,24,26 The introduction of the somewhat responsive cellular phenotype into our study design increased its analytical precision and may have eliminated some of the well-known methodical limitations associated with cell culture studies.…”

Section: Discussionmentioning

confidence: 99%

Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib

Halatsch

Low

Mursch

et al. 2009

JNS

View full text Add to dashboard Cite

Object The authors have previously reported that erlotinib, an EGFR tyrosine kinase inhibitor, exerts widely variable antiproliferative effects on 9 human glioblastoma multiforme (GBM) cell lines in vitro and in vivo. These effects were independent of EGFR baseline expression levels, raising the possibility that more complex genetic properties form the molecular basis of the erlotinib-sensitive and erlotinib-resistant GBM phenotypes. The aim of the present study was to determine candidate genes for mediating the cellular response of human GBMs to erlotinib. Methods Complementary RNA obtained in cell lines selected to represent the sensitive, somewhat responsive, and resistant phenotypes were hybridized to CodeLink Human Whole Genome Bioarrays. Results Expression analysis of 814 prospectively selected genes involved in major proliferation and apoptosis signaling pathways identified 19 genes whose expression significantly correlated with phenotype. Functional annotation analysis revealed that 2 genes (DUSP4 and STAT1) were significantly associated with sensitivity to erlotinib, and 10 genes (CACNG4, FGFR4, HSPA1B, HSPB1, NFATC1, NTRK1, RAC1, SMO, TCF7L1, and TGFB3) were associated with resistance to erlotinib. Moreover, 5 genes (BDNF, CARD6, FOSL1, HSPA9B, and MYC) involved in antiapoptotic pathways were unexpectedly found to be associated with sensitivity. Gene expressions were confirmed by quantitative polymerase chain reaction. Conclusions Based on an analysis of gene expressions in cell lines with sensitive, somewhat responsive, and resistant phenotypes, the authors propose candidate genes for GBM response to erlotinib. The 10 gene candidates for conferring GBM resistance to erlotinib may represent therapeutic targets for enhancing the efficacy of erlotinib against GBMs. Five additional genes warrant further investigation into their role as putative cotargets of erlotinib.

show abstract

“…Reverse transcription-PCR experiments have located Shh mRNA in the cortex and tectum of E-13.5 mice, with continued expression through P5. Shh is expressed in progenitors of the subventricular zone (Charytoniuk et al, 2002) and stimulates proliferation of precursor cells in the ventricular zones of the telencephalon and mesencephalon and normal levels of proliferation can be attenuated with Shh inhibitors (Dahmane et al, 2001). More recent experiments have directly linked Shh signaling to proliferation of adult neural stem cells in the rat hippocampus.…”

Section: Shh Is An Important Mitogen In the Cnsmentioning

confidence: 99%

Persistent Progenitors at the Retinal Margin ofptc+/- Mice

Moshiri¹,

Reh²

2004

J. Neurosci.

132

View full text Add to dashboard Cite

The hedgehog signaling pathway is a key regulator of neural development, affecting both proliferation and differentiation of neural progenitors. Sonic hedgehog (Shh) is a mitogenic factor for retinal progenitors in vitro. To determine whether this signaling system is important in vivo for regulating retinal progenitor proliferation, we analyzed mice with a single functional allele of the Shh receptor patched ( ptc). We found that ptc؉/؊ mice had increased numbers of neural progenitors at every stage of retinal development that we examined. In addition, these mice had persistent progenitors at the retinal margin for up to 3 months of age, reminiscent of the ciliary marginal zone of lower vertebrates. To test whether the progenitors at the retinal margin of ptc؉/؊ mice could be induced to regenerate retinal neurons in response to damage, we bred ptc؉/؊ mice onto a retinal degeneration background (pro23his rhodopsin transgenic) and labeled newly generated cells with combined immunohistochemistry for bromodeoxyuridine and retinal neuron and photoreceptorspecific markers. We found newly generated neurons and photoreceptors at the retinal margin in ptc؉/؊;pro23his mice. We propose that the Shh pathway may act as a regulator of both prenatal and postnatal retinal growth.

show abstract

Intrastriatal sonic hedgehog injection increases Patched transcript levels in the adult rat subventricular zone

Cited by 41 publications

References 34 publications

Sonic hedgehog controls stem cell behavior in the postnatal and adult brain

Sonic hedgehog controls stem cell behavior in the postnatal and adult brain

Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib

Persistent Progenitors at the Retinal Margin ofptc+/- Mice

Contact Info

Product

Resources

About