Protocadherin a gene cluster is required for myelination and oligodendrocyte development

Yu, Yu; Suo, Lun; Wu, Qiang

doi:10.3724/sp.j.1141.2012.04362

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…Mapping contact densities using 100-1,000 kb insulation squares showed that the locus is generally open above 500 kb. Higher expression of Pcdha and Pcdhb coincides with increased long-range contacts between the three clusters in neurons 16 and OLGs 17 and with additional long-range contacts with the highly expressed Fgf1 gene in OLGs. We also discovered contacts spanning tens of megabases in brain cells.…”

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confidence: 88%

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Cell-type specialization is encoded by specific chromatin topologies

Winick-Ng

Kukalev

Harabula

et al. 2021

Nature

149

139

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The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1–3. Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated cell sorting from cortical tissues pooled from different animals and from dissociated whole hippocampi4–6. However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation7, are invisible with such approaches8. Here we developed immunoGAM, an extension of genome architecture mapping (GAM)2,9, to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals. GAM is a ligation-free technology that maps genome topology by sequencing the DNA content from thin (about 220 nm) nuclear cryosections. Chromatin interactions are identified from the increased probability of co-segregation of contacting loci across a collection of nuclear slices. ImmunoGAM expands the scope of GAM to enable the selection of specific cell types using low cell numbers (approximately 1,000 cells) within a complex tissue and avoids tissue dissociation2,10. We report cell-type specialized 3D chromatin structures at multiple genomic scales that relate to patterns of gene expression. We discover extensive ‘melting’ of long genes when they are highly expressed and/or have high chromatin accessibility. The contacts most specific of neuron subtypes contain genes associated with specialized processes, such as addiction and synaptic plasticity, which harbour putative binding sites for neuronal transcription factors within accessible chromatin regions. Moreover, sensory receptor genes are preferentially found in heterochromatic compartments in brain cells, which establish strong contacts across tens of megabases. Our results demonstrate that highly specific chromatin conformations in brain cells are tightly related to gene regulation mechanisms and specialized functions.

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confidence: 88%

“…> 3). PGN-selected TFs (33) are shown in blue, DNselected TFs (17) are shown in green. A list of selected TFs are shown below, with TF motifs continuing after the TF enrichment analysis in (f) coloured in blue (PGNs) or green (DNs).…”

Section: Reporting Summarymentioning

confidence: 99%

Cell-type specialization is encoded by specific chromatin topologies

Winick-Ng

Kukalev

Harabula

et al. 2021

Nature

149

139

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“…Specifically, Pcdhα expression is negatively correlated with the increasing expression levels of myelination markers during development (Morishita et al, 2004). In addition, deletion of the Pcdhα cluster in mice results in delayed oligodendrocyte maturation and defects in myelination (Yu et al, 2012). Moreover, imaging by transmission electron microscopy revealed the reduced ratio of myelinated nerve fibers and abnormal myelin sheaths in the Pcdhα deletion mice (Lu et al, 2018).…”

Section: A Role Of Pcdhα In Myelinationmentioning

confidence: 99%

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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“…The γ--Pcdhs are the only family of the clustered Pcdhs to exhibit a severe knockout phenotype: Pcdha KOs have only exhibited minor abnormalities: enhanced contextual fear conditioning and spatial working memory [this work was done with two Pcdha knockdown lines; (Fukuda et al, 2008)]; minor axon pathfinding errors such as aberrant distribution of serotonergic projection, abnormal sorting of olfactory sensory neuron axons into the glomeruli of the olfactory bulb, and impaired retinogeniculate axonal terminals in the lateral geniculate (Hasegawa et al, 2008;Katori et al, 2009;Meguro et al, 2015); reduction of myelin basic protein through the central nervous system (Yu et al, 2012); and perturbation in orientation and direction selectivity within the visual system (Meguro et al, 2015). For this reason, we have focused on γ--Pcdhs in our work.…”

Section: What Is the Actual Diversity Of Pcdh Tetramers?mentioning

confidence: 99%

Branching out by sticking together

Keeler¹

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Department of Biology, for all the work they did, often hidden behind the scenes, vital to the running of these programs. I thank the members of my thesis committee. Josh, thank you for the years of mentorship and gracious support through the highs and lows of research and life. Drs. DeMali, Frank, Green, and Stipp, thank you for the advice and questions over the years; they have helped strengthen my projects.

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Protocadherin a gene cluster is required for myelination and oligodendrocyte development

Cited by 4 publications

References 9 publications

Cell-type specialization is encoded by specific chromatin topologies

Cell-type specialization is encoded by specific chromatin topologies

Clustered Protocadherins Emerge as Novel Susceptibility Loci for Mental Disorders

Branching out by sticking together

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