Wiring the Brain by Clustered Protocadherin Neural Codes

Wu, Qiang; Jia, Zhilian

doi:10.1007/s12264-020-00578-4

Cited by 34 publications

(32 citation statements)

References 121 publications

(276 reference statements)

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“…The three Pcdh clusters contain tandem arrays of CTCF binding sites (CBS) in both gene promoters and enhancers ( Figure 1A) (Golan-Mashiach et al, 2012;Guo et al, 2012;Monahan et al, 2012). CTCF/cohesin-mediated long-range chromatin interactions between these CBS elements determine the stochastic and combinatorial expression of diverse cPcdh repertoires on the cell surface (Wu and Jia, 2020). Differential expression of cPcdh genes in individual neurons is regulated by epigenetic modifications, such as DNA methylation and H3K9me3 histone modification in the promoter region (Guo et al, 2012;Toyoda et al, 2014;Chen et al, 2015;Jiang et al, 2017;Wada et al, 2018).…”

Section: Molecular Mechanisms For Generating Diversified Neural Identmentioning

confidence: 99%

“…Without CTCF binding, cPcdh promoters cannot form long-range chromatin contacts with remote enhancers and thus cannot be activated (Guo et al, 2012;Canzio et al, 2019). It is this higher-order chromatin architecture that determines the Pcdh promoter choice in the cell nucleus (Wu and Jia, 2020).…”

Section: Molecular Mechanisms For Generating Diversified Neural Identmentioning

confidence: 99%

“…Isoforms of Pcdhα and Pcdhγ could be cleaved by the metalloproteinase ADAM10 and γ-secretase to release the intracellular domain which translocates into the nucleus to regulate gene expression (Haas et al, 2005;Hambsch et al, 2005;Reiss et al, 2006;Bonn et al, 2007;Buchanan et al, 2010). Thus, diverse extracellular signals can converge on the same intracellular signaling pathway through the common CD shared by members of Pcdhα or Pcdhγ (Wu and Maniatis, 1999;Wu et al, 2001;Schalm et al, 2010;Fan et al, 2018) (reviewed in Wu and Jia, 2020). In addition, the intracellular domains of Pcdhα and Pcdhγ can bind to several kinases including FAK (focal adhesion kinase), Pyk2 (proline-rich tyrosine kinase 2), and Ret (receptor tyrosine kinase rearranged during transformation) ( Figure 2) (Chen et al, 2009;Schalm et al, 2010;Garrett et al, 2012;Suo et al, 2012;Keeler et al, 2015).…”

Section: Self-recognition and Non-self Discrimination On The Cell Surmentioning

confidence: 99%

“…The Pcdh β and γ proteins, on the other hand, do not contain the WIRS motif. However, they may also modulate actin dynamics through forming cis-heterodimers with Pcdhα (Thu et al, 2014;Rubinstein et al, 2015;Goodman et al, 2017), or through the shared downstream effector Pyk2 (Chen et al, 2009;Suo et al, 2012) (reviewed in Wu and Jia, 2020).…”

Section: A Signaling Pathway Linking Clustered Pcdhs To Lamellipodialmentioning

confidence: 99%

“…We propose that epigenetic dysregulation of cPcdhs underlies many mental disorders. We refer interested readers to other recent reviews describing various aspects of cPcdhs (Flaherty and Maniatis, 2020;Honig and Shapiro, 2020;Pancho et al, 2020;Sanes and Zipursky, 2020;Wu and Jia, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Clustered Protocadherins Emerge as Novel Susceptibility Loci for Mental Disorders

Jia

2020

Front. Neurosci.

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The clustered protocadherins (cPcdhs) are a subfamily of type I single-pass transmembrane cell adhesion molecules predominantly expressed in the brain. Their stochastic and combinatorial expression patterns encode highly diverse neural identity codes which are central for neuronal self-avoidance and non-self discrimination in brain circuit formation. In this review, we first briefly outline mechanisms for generating a tremendous diversity of cPcdh cell-surface assemblies. We then summarize the biological functions of cPcdhs in a wide variety of neurodevelopmental processes, such as neuronal migration and survival, dendritic arborization and self-avoidance, axonal tiling and even spacing, and synaptogenesis. We focus on genetic, epigenetic, and 3D genomic dysregulations of cPcdhs that are associated with various neuropsychiatric and neurodevelopmental diseases. A deeper understanding of regulatory mechanisms and physiological functions of cPcdhs should provide significant insights into the pathogenesis of mental disorders and facilitate development of novel diagnostic and therapeutic strategies.

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Section: Molecular Mechanisms For Generating Diversified Neural Identmentioning

confidence: 99%

Section: Molecular Mechanisms For Generating Diversified Neural Identmentioning

confidence: 99%

Section: Self-recognition and Non-self Discrimination On The Cell Surmentioning

confidence: 99%

Section: A Signaling Pathway Linking Clustered Pcdhs To Lamellipodialmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clustered Protocadherins Emerge as Novel Susceptibility Loci for Mental Disorders

Jia

2020

Front. Neurosci.

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Meaning Relies on Codes but Depends on Agents

Prinz

2024

Pathways to the Origin and Evolution of Meanings in the Universe

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Transition to Piscivory Seen Through Brain Transcriptomics in a Juvenile Percid Fish: Complex Interplay of Differential Gene Transcription, Alternative Splicing, and ncRNA Activity

Symonová,

Jůza,

Tesfaye

et al. 2024

J Exp Zool Pt A

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Pikeperch (Sander Lucioperca) belongs to main predatory fish species in freshwater bodies throughout Europe playing the key role by reducing planktivorous fish abundance. Two size classes of the young‐of‐the‐year (YOY) pikeperch are known in Europe and North America. Our long‐term fish survey elucidates late‐summer size distribution of YOY pikeperch in the Lipno Reservoir (Czechia) and recognizes two distinct subcohorts: smaller pelagic planktivores heavily outnumber larger demersal piscivores. To explore molecular mechanisms accompanying the switch from planktivory to piscivory, we compared brain transcriptomes of both subcohorts and identified 148 differentially transcribed genes. The pathway enrichment analyses identified the piscivorous phase to be associated with genes involved in collagen and extracellular matrix generation with numerous Gene Ontology (GO), while the planktivorous phase was associated with genes for non‐muscle‐myosins (NMM) with less GO terms. Transcripts further upregulated in planktivores from the periphery of the NMM network were Pmchl, Pomcl, and Pyyb, all involved also in appetite control and producing (an)orexigenic neuropeptides. Noncoding RNAs were upregulated in transcriptomes of planktivores including three transcripts of snoRNA U85. Thirty genes mostly functionally unrelated to those differentially transcribed were alternatively spliced between the subcohorts. Our results indicate planktivores as potentially driven by voracity to initiate the switch to piscivory, while piscivores undergo a dynamic brain development. We propose a spatiotemporal spreading of juvenile development over a longer period and larger spatial scales through developmental plasticity as an adaptation to exploiting all types of resources and decreasing the intraspecific competition.

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Wiring the Brain by Clustered Protocadherin Neural Codes

Cited by 34 publications

References 121 publications

Clustered Protocadherins Emerge as Novel Susceptibility Loci for Mental Disorders

Clustered Protocadherins Emerge as Novel Susceptibility Loci for Mental Disorders

Meaning Relies on Codes but Depends on Agents

Transition to Piscivory Seen Through Brain Transcriptomics in a Juvenile Percid Fish: Complex Interplay of Differential Gene Transcription, Alternative Splicing, and ncRNA Activity

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