Bestman JE , Cline HT .

R01 EY011261 NEI NIH HHS

	Fig. 1. CPEB is required for dendritic arbor growth in vivo. (A–D) Time-lapse in vivo two-photon images of tectal neurons and their three-dimensional (3D) reconstructions, collected daily over 3 days. (E-G) Quantification of dendritic morphology showing total dendritic branch length (TDBL) (E), branch-tip number (F), and 3D Sholl analysis (G). (E) Compared to control cells, the dendritic growth of delCPEB-expressing neurons, but not CPEB or rbdCPEB-expressing neurons, is significantly impaired by day 2 and 3. (F) By day 3, only delCPEB-expressing neurons have significantly fewer branch tips compared to control neurons. (G) Sholl analysis of 3-day cells illustrating the radial distribution of the branches of the dendritic arbor. Shown are the average number of branch intersections at 10-μm intervals beyond the soma. Control, n = 11; CPEB, n = 12; delCPEB n = 10; rbdCPEB = 12; *, P ≤ 0.05. Values given in Table S2.
	Fig. 2. CPEB function is required for experience-dependent increased dendritic growth. (A-D) Time-lapse in vivo two photon images collected at 4-h intervals over 8 h, and 3D reconstructions showing terminal branches that are lost (pink), appeared transiently at the fourth hour (green), and are gained (blue) over the 4-h periods without or with visual stimulation (indicated with light-bulb icon) for tectal neurons. (E–H) Quantification of dendritic morphology. During the 4 h of light stimulation, control and CPEB-expressing neurons show a significant increase in TDBL (E) and branch-tip number (F). Individual cell's changes in TDBL (G) and branch-tip number (H) are plotted in gray, averages are plotted in black. Control and CPEB-expressing cells show significant changes in TDBL. Only CPEB-expressing cells show a significant change in branch-tip number. (I–L) Quantification of identified branch dynamics. Proportion of branches newly added (I) and lost (J) during each 4-h. (I) delCPEB-expressing cells add significantly fewer branches during the light-stimulation period compared to control neurons. There were no differences in the proportion of branches lost between groups (J). (K) The average increase in branch length of delCPEB cells is less than that of control cells in both the dark and during the light stimulus. CPEB cells also added significantly less average branch length during the visual stimulation period. (L) The average amount that delCPEB-retracting branches lost was less than control cells in both the dark and during the light stimulation. Control, n = 12; CPEB, n = 10; delCPEB, n = 14; rbdCPEB = 11; *, P < 0.05. Values given in Tables S3–S5.
	Fig. 3. Altering CPEB function reduces amplitude but not frequency of AMPA receptor mEPSCs. (A) Representative traces and examples of average mEPSCs. (B) Quantification of mEPSC amplitude (*, P < Control, n = 32; CPEB, n = 28; delCPEB n = 31.
	Fig. 4. Altering CPEB expression interferes with tectal cell performance in the visual circuit. (A–C) Whole-cell recordings of visual responses over the complete 2.5 s of the off responses. Each column shows recordings from the same cell for each 10-dB increase in intensity. Twenty responses are superimposed in gray with the average response in black. (D–F) Spontaneous activity recorded during the dark-adaptation period. Gray areas are expanded in the insets. Bursting activity is only seen in control cells. (G) Quantification of average charge transferred (Q) over 500 ms following light off for each stimulus intensity. Compared to control neurons, delCPEB-expressing cells showed significantly lower Q for each intensity tested. CPEB cells were significantly different at the stronger relative intensities. n = 6–10 cells for each intensity for control, CPEB and delCPEB groups. (H and I) Quantification of spontaneous synaptic activity recorded in the absence of TTX. Distribution and means (inset) for the single event amplitudes (H) and inter-event intervals (IEI) (I) were significantly shifted toward smaller values for both delCPEB and CPEB-expressing neurons compared to control cells. n = 1,190 events and 10 neurons per cell group. *, P < 0.05. Values given in Tables S6 and S7.

Aizenman, Enhanced visual activity in vivo forms nascent synapses in the developing retinotectal projection. 2007, Pubmed, Xenbase

Aizenman, Enhanced visual activity in vivo forms nascent synapses in the developing retinotectal projection. 2007, Pubmed , Xenbase
Alarcon, Selective modulation of some forms of schaffer collateral-CA1 synaptic plasticity in mice with a disruption of the CPEB-1 gene. 2004, Pubmed , Xenbase
Atkins, Cytoplasmic polyadenylation element binding protein-dependent protein synthesis is regulated by calcium/calmodulin-dependent protein kinase II. 2004, Pubmed
Berger-Sweeney, Reduced extinction of hippocampal-dependent memories in CPEB knockout mice. 2006, Pubmed
Bestman, In vivo single-cell electroporation for transfer of DNA and macromolecules. 2006, Pubmed , Xenbase
Bramham, Dendritic mRNA: transport, translation and function. 2007, Pubmed
Costa, The Drosophila fragile X protein functions as a negative regulator in the orb autoregulatory pathway. 2005, Pubmed
Derkach, Regulatory mechanisms of AMPA receptors in synaptic plasticity. 2007, Pubmed
Di Nardo, Dendritic localization and activity-dependent translation of Engrailed1 transcription factor. 2007, Pubmed
Du, Activity-dependent polyadenylation in neurons. 2005, Pubmed , Xenbase
Ewald, Roles of NR2A and NR2B in the development of dendritic arbor morphology in vivo. 2008, Pubmed , Xenbase
Ferrari, The fragile X mental retardation protein-RNP granules show an mGluR-dependent localization in the post-synaptic spines. 2007, Pubmed
Gao, Posttranscriptional control of neuronal development by microRNA networks. 2008, Pubmed
Haas, AMPA receptors regulate experience-dependent dendritic arbor growth in vivo. 2006, Pubmed , Xenbase
Haas, Targeted electroporation in Xenopus tadpoles in vivo--from single cells to the entire brain. 2002, Pubmed , Xenbase
Huang, N-methyl-D-aspartate receptor signaling results in Aurora kinase-catalyzed CPEB phosphorylation and alpha CaMKII mRNA polyadenylation at synapses. 2002, Pubmed , Xenbase
Huang, Facilitation of dendritic mRNA transport by CPEB. 2003, Pubmed
Huang, CPEB3 and CPEB4 in neurons: analysis of RNA-binding specificity and translational control of AMPA receptor GluR2 mRNA. 2006, Pubmed , Xenbase
Keene, RNA regulons: coordination of post-transcriptional events. 2007, Pubmed
Keleman, Function of the Drosophila CPEB protein Orb2 in long-term courtship memory. 2007, Pubmed
Kelleher, Translational regulatory mechanisms in persistent forms of synaptic plasticity. 2004, Pubmed
Kiebler, Neuronal RNA granules: movers and makers. 2006, Pubmed
Lisman, The molecular basis of CaMKII function in synaptic and behavioural memory. 2002, Pubmed
Liu, The cytoplasmic polyadenylation element binding protein and polyadenylation of messenger RNA in Aplysia neurons. 2003, Pubmed
McEvoy, Cytoplasmic polyadenylation element binding protein 1-mediated mRNA translation in Purkinje neurons is required for cerebellar long-term depression and motor coordination. 2007, Pubmed
Mendez, Translational control by CPEB: a means to the end. 2001, Pubmed , Xenbase
Moore, From birth to death: the complex lives of eukaryotic mRNAs. 2005, Pubmed
Ouyang, Tetanic stimulation leads to increased accumulation of Ca(2+)/calmodulin-dependent protein kinase II via dendritic protein synthesis in hippocampal neurons. 1999, Pubmed
Pfeiffer, Current advances in local protein synthesis and synaptic plasticity. 2006, Pubmed
Rajan, Glutamate receptor activity is required for normal development of tectal cell dendrites in vivo. 1998, Pubmed , Xenbase
Reverte, CPEB degradation during Xenopus oocyte maturation requires a PEST domain and the 26S proteasome. 2001, Pubmed , Xenbase
Richter, CPEB: a life in translation. 2007, Pubmed , Xenbase
Ruthazer, Stabilization of axon branch dynamics by synaptic maturation. 2006, Pubmed , Xenbase
Sanchez, BDNF increases synapse density in dendrites of developing tectal neurons in vivo. 2006, Pubmed , Xenbase
Shin, Rapid, activity-induced increase in tissue plasminogen activator is mediated by metabotropic glutamate receptor-dependent mRNA translation. 2004, Pubmed
SHOLL, Dendritic organization in the neurons of the visual and motor cortices of the cat. 1953, Pubmed
Si, A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia. 2003, Pubmed , Xenbase
Sin, Dendrite growth increased by visual activity requires NMDA receptor and Rho GTPases. 2002, Pubmed , Xenbase
Sutton, Dendritic protein synthesis, synaptic plasticity, and memory. 2006, Pubmed
Ule, RNA binding proteins and the regulation of neuronal synaptic plasticity. 2006, Pubmed
Van Keuren-Jensen, Visual experience regulates metabotropic glutamate receptor-mediated plasticity of AMPA receptor synaptic transmission by homer1a induction. 2006, Pubmed , Xenbase
Weiler, Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses. 2004, Pubmed
Wells, A role for the cytoplasmic polyadenylation element in NMDA receptor-regulated mRNA translation in neurons. 2001, Pubmed
Wong, Activity-dependent regulation of dendritic growth and patterning. 2002, Pubmed
Wu, CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of alpha-CaMKII mRNA at synapses. 1998, Pubmed , Xenbase
Wu, Stabilization of dendritic arbor structure in vivo by CaMKII. 1998, Pubmed , Xenbase
Wu, Maturation of a central glutamatergic synapse. 1996, Pubmed , Xenbase
Zhang, Visual input induces long-term potentiation of developing retinotectal synapses. 2000, Pubmed , Xenbase