Dact1 Is a Postsynaptic Protein Required for Dendrite, Spine, and Excitatory Synapse Development in the Mouse Forebrain

Okerlund, Nathan D.; Kivimäe, Saul; Tong, Cheuk Ka; Peng, I-Feng; Ullian, Erik M.; Cheyette, Benjamin N.R.

doi:10.1523/jneurosci.0354-10.2010

Cited by 35 publications

(51 citation statements)

References 36 publications

(51 reference statements)

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“…Dact1 is expressed in differentiating forebrain neurons, and its loss causes reductions in dendrite arbor complexity, dendritic spine maturity and glutamatergic synapse formation [30] similar to the Vangl2 mutant phenotypes reported here. Nonetheless, neurons from Vangl2 Lp/+ ; Dact1 -/- mice had no rescue of dendrite complexity (fig.…”

Section: Resultsmentioning

confidence: 55%

“…Genetic disruption of other PCP genes in mammals, including Dvl1 [35] and Dact1 [30], causes similar phenotypes. Given the widespread neural expression of Vangl2 and several other PCP genes during prenatal development, postnatal development and in the mature brain, it is plausible that the neural functions of these molecules are similarly widespread and continuous over the lifespan.…”

Section: Discussionmentioning

confidence: 99%

“…Dissociated neurons were obtained from embryos, fixed, transfected with pEGFP-C1 (Clontech) and immunostained for synaptic markers as previously described [29,30]. Hippocampal cultures were used where possible because of the ease of producing populations of predominantly pyramidal neurons and prior validation as a model system relevant to dendrite, spine and synapse formation in the forebrain [31].…”

Section: Methodsmentioning

confidence: 99%

“…Images were analyzed with ImageJ software (NIH). Sholl analysis, dendritic spine binning and spine and synapse quantification were performed as previously described [30]. …”

Section: Methodsmentioning

confidence: 99%

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The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain

Okerlund

Stanley²,

Cheyette³

2016

Complex Psychiatry

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The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice. Given increasing evidence linking psychiatric pathophysiology to these subneuronal sites and structures, our findings underscore the relevance of core PCP proteins including Vangl2 to the underlying biology of major mental illnesses and their treatment.

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Section: Resultsmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Images were analyzed with ImageJ software (NIH). Sholl analysis, dendritic spine binning and spine and synapse quantification were performed as previously described [30]. …”

Section: Methodsmentioning

confidence: 99%

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The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain

Okerlund

Stanley²,

Cheyette³

2016

Complex Psychiatry

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“…Canonical Wnt signaling is mediated through itnracellular β-catenin whereas, the non-canonical Wnt pathway is β-catenin-independent and signals through core planar cell polarity (PCP) proteins including Prickle (19,20). Transgenic mice with manipulations in Wnt genes display a variety of behavioral abnormalities including seizures, abnormal learning, and repetitive behaviors (18,(21)(22)(23). Accordingly, ASD-like phenotypes in mice were linked to mutations in genes of the Wnt/PCP pathway (21,22).…”

Section: Introductionmentioning

confidence: 99%

Erratum: Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction

Sowers¹,

Loo²,

Wu³

et al. 2013

Mol Psychiatry

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Author Contributions: LPS contributed to all experiments, planning, and writing of the paper. LL performed all in vitro electrophysiology. YW performed in vivo electrophysiology. LL, LPS and DPM analyzed all the electrophysiology data. EC performed mouse behavioral experiments. YMU and JU performed a part of primary hippocampal neuron cultures. SW performed western blot experiments. JRM, HEL, LP, TW, XY and KM aided in the collection and sequencing of human DNA. PF, NU and SW conducted production and breeding of mice of different genotypes used in this study. AJS assisted in all immunocytochemistry experiments and analysis. GBR, DPM, and JM provided reagents, supervised experiments and analysis, and aided in manuscript writing. JAW provided all behavioral equipment. JAW and DPM provided scientific input to the study design. BWD provided statistical analysis for whole exome sequencing data. All authors contributed to the writing of this manuscript. AGB supervised all aspects of the project design, execution and writing of the paper. The datasets used for the analysis described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000298.v1.p1, under dbGAP Research Project #4357 (Variation in PRICKLE2 and related Genes in Autism) to AGB. The data set(s) were deposited by the ARRA Autism Sequencing Collaborative, an ARRA funded research initiative. AbstractAutism spectrum disorders (ASDs) have been suggested to arise from abnormalities in the canonical and non-canonical Wnt signaling pathways. However, a direct connection between a human variant in a Wnt pathway gene and ASD-relevant brain pathology has not been established. Prickle2 (Pk2) is a post-synaptic non-canonical Wnt signaling protein shown to interact with post synaptic density 95 (PSD-95). Here we show that mice with disruption in Prickle2 display behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility. Prickle2 disruption in mouse hippocampal neurons led to reductions in dendrite branching, synapse number, and post-synaptic density size. Consistent with these findings, Prickle2 null neurons show decreased frequency and size of spontaneous miniature synaptic currents. These behavioral and physiological abnormalities in Prickle2 disrupted mice are consistent with ASD-like phenotypes present in other mouse models of ASDs. In 384 individuals with autism, we identified two with distinct, heterozygous, rare, non-synonymous PRICKLE2 variants (p.E8Q and p.V153I) that were shared by their affected siblings and inherited paternally. Unlike wild-type PRICKLE2, the PRICKLE2 variants found in ASD patients exhibit deficits in morphological and electrophysiological assays. These data suggest that these PRICKLE2 variants cause a critical loss of PRICKLE2 function. The data presented here provide new insight into the biological roles of Prickle2, its behavioral importance, and suggest disruptions in non-canonical Wnt genes such as PRICKLE2 may contribu...

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As above, so below: Whole transcriptome profiling demonstrates strong molecular similarities between avian dorsal and ventral pallial subdivisions

Gedman

Haase

Durieux

et al. 2021

J of Comparative Neurology

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Over the last two decades, beginning with the Avian Brain Nomenclature Forum in 2000, major revisions have been made to our understanding of the organization and nomenclature of the avian brain. However, there are still unresolved questions on avian pallial organization, particularly whether the cells above the vestigial ventricle represent distinct populations to those below it or similar populations. To test these two hypotheses, we profiled the transcriptomes of the major avian pallial subdivisions dorsal and ventral to the vestigial ventricle boundary using RNA sequencing and a new zebra finch genome assembly containing about 22,000 annotated, complete genes. We found that the transcriptomes of neural populations above and below the ventricle were remarkably similar. Each subdivision in dorsal pallium (Wulst) had a corresponding molecular counterpart in the ventral pallium (dorsal ventricular ridge). In turn, each corresponding subdivision exhibited shared gene co‐expression modules that contained gene sets enriched in functional specializations, such as anatomical structure development, synaptic transmission, signaling, and neurogenesis. These findings are more in line with the continuum hypothesis of avian brain subdivision organization above and below the vestigial ventricle space, with the pallium as a whole consisting of four major cell populations (intercalated pallium, mesopallium, hyper‐nidopallium, and arcopallium) instead of seven (hyperpallium apicale, interstitial hyperpallium apicale, intercalated hyperpallium, hyperpallium densocellare, mesopallium, nidopallium, and arcopallium). We suggest adopting a more streamlined hierarchical naming system that reflects the robust similarities in gene expression, neural connectivity motifs, and function. These findings have important implications for our understanding of overall vertebrate brain evolution.

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Dact1 Is a Postsynaptic Protein Required for Dendrite, Spine, and Excitatory Synapse Development in the Mouse Forebrain

Cited by 35 publications

References 36 publications

The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain

The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain

Erratum: Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction

As above, so below: Whole transcriptome profiling demonstrates strong molecular similarities between avian dorsal and ventral pallial subdivisions

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