2006
DOI: 10.1016/j.cell.2006.07.037
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Presenilin-Dependent ErbB4 Nuclear Signaling Regulates the Timing of Astrogenesis in the Developing Brain

Abstract: Embryonic multipotent neural precursors are exposed to extracellular signals instructing them to adopt different fates, neuronal or glial. However, the mechanisms by which precursors integrate these signals to make timely fate choices remained undefined. Here we show that direct nuclear signaling by a receptor tyrosine kinase inhibits the responses of precursors to astrocyte differentiation factors while maintaining their neurogenic potential. Upon neuregulin-induced activation and presenilin-dependent cleavag… Show more

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Cited by 324 publications
(290 citation statements)
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References 41 publications
(45 reference statements)
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“…21, 55, 60 and 180 kDa) (unpublished data); 2) the ErbB4 proteins we studied were previously detected in non-human primate brains with minimal PMIs (Thompson et al 2007); 3) prefrontal cortical quantities of the examined smaller NRG1 and ErbB4 immunoreactive bands rarely correlated with PMI among the entire cohort or in any individual diagnostic group. We speculate the additional fragments detected for NRG1 and ErbB4 represent novel intracellular cleavage products, since the antibodies used recognize intracellular portions of NRG1 and ErbB4, both of which can be cleaved to release intracellular molecules (Bao et al 2004;Ni et al 2001;Sardi et al 2006;Zhang et al 2006). Alternatively, these smaller immunoreactive fragments may represent NRG1-like or ErbB4-like proteins, though the presence of multiple immunoreactive bands for both NRG1 and ErbB4 is not unexpected (Bao et al 2004;Carroll et al 1997;Cote et al 2005;Frenzel and Falls 2001;Hahn et al 2006;Hirata et al 2007;Law et al 2004;Lebrasseur et al 2003;Thompson et al 2007).…”
Section: Effects Of Possible Confounding Variables On the Examined Nrmentioning
confidence: 91%
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“…21, 55, 60 and 180 kDa) (unpublished data); 2) the ErbB4 proteins we studied were previously detected in non-human primate brains with minimal PMIs (Thompson et al 2007); 3) prefrontal cortical quantities of the examined smaller NRG1 and ErbB4 immunoreactive bands rarely correlated with PMI among the entire cohort or in any individual diagnostic group. We speculate the additional fragments detected for NRG1 and ErbB4 represent novel intracellular cleavage products, since the antibodies used recognize intracellular portions of NRG1 and ErbB4, both of which can be cleaved to release intracellular molecules (Bao et al 2004;Ni et al 2001;Sardi et al 2006;Zhang et al 2006). Alternatively, these smaller immunoreactive fragments may represent NRG1-like or ErbB4-like proteins, though the presence of multiple immunoreactive bands for both NRG1 and ErbB4 is not unexpected (Bao et al 2004;Carroll et al 1997;Cote et al 2005;Frenzel and Falls 2001;Hahn et al 2006;Hirata et al 2007;Law et al 2004;Lebrasseur et al 2003;Thompson et al 2007).…”
Section: Effects Of Possible Confounding Variables On the Examined Nrmentioning
confidence: 91%
“…The ErbB4 antibody also reacts with a carboxy terminal region present in the intracellular portion of ErbB4 and can recognize full-length ErbB4 and intracellular cleavage products of the receptor (Garcia et al 2000;Hahn et al 2006;Sardi et al 2006;Thompson et al 2007). Among the samples, this antibody detected ErbB4 immunoreactive bands at roughly 180 and 80kDa ( Figure 2B), which correspond to full-length ErbB4 and the cleaved ErbB4 intracellular domain, respectively (Elenius et al 1997;Elenius et al 1999;Hahn et al 2006;Plowman et al 1993;Vecchi et al 1996).…”
Section: Detected Nrg1 and Erbb4 Immunoreactive Bandsmentioning
confidence: 99%
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“…This process is balanced by the WW domain protein WWOX that can sequester s80 in the cytosol [78]. Supporting the in vivo role for s80 in transcriptional regulation, s80 has been shown to form a complex with the adaptor protein TAB2 and the nuclear co-repressor N-CoR causing repression of genes involved in astrogenesis [79].…”
Section: Nuclear Translocation Of Erbb Membersmentioning
confidence: 95%