Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly

Mountoufaris, George; Chen, Weisheng V.; Hirabayashi, Yusuke; O’Keeffe, Sean; Chevée, Maxime; Nwakeze, Chiamaka L.; Polleux, Franck; Maniatis, Tom

doi:10.1126/science.aai8801

Cited by 148 publications

(201 citation statements)

References 33 publications

Supporting

Mentioning

181

Contrasting

Order By: Relevance

“…The neuronal self-avoidance and tiling functions are consistent with Pcdhs initiating repulsion [2–4], while Pcdhs also play other roles such as promoting the complexity of a neuron’s dendritic arbor [44]. We note that although this review focuses on the role of Pcdhs in neuronal self-avoidance in promoting repulsion, the cis and trans interactions formed between Pcdhs that we have described here are also relevant to the adhesive functions of Pcdhs.…”

Section: Two Models Of the Pcdh Recognition Complex And Associatedmentioning

confidence: 69%

“…For example, recent studies have shown that unique interaction of PcdhγC3 with Axin1 inhibits Wnt signaling [70]. In general, a more complex picture of Pcdh gene expression is emerging, in which distinct Pcdh gene clusters are expressed in different types of neurons, and the alternate and C-type isoforms are differentially expressed during the development of neural circuits [4, 16, 60]. …”

Section: Discussionmentioning

confidence: 99%

“…The formation of such complex neural circuits depends on a limited repertoire of guidance cues and cell surface receptors. Clustered protocadherins (Pcdhs) are a family of highly diverse cell-surface receptors that are thought to provide individual neurons with single-cell-specific molecular “barcodes”, which provide unique cell surface identities required for neurite self-avoidance [2–4]. Although recent studies have demonstrated that Pcdhs have additional roles in regulating neuronal survival, synaptogenesis, dendritic arborization, and neuronal tiling [2–17] —this review focuses primarily on the role of Pcdhs in neuronal self-avoidance that in turn requires that neurons be able to distinguish “self” from “non-self”.…”

Section: Introductionmentioning

confidence: 99%

“…In the fly neuronal identity is defined by the expression of single-cell-specific subsets of Dscam1 protein isoforms, generated by stochastic alternative RNA splicing [31–34]. In vertebrates, neuronal identity is provided by stochastic expression of single-cell-specific subsets of Pcdh isoforms [4, 22–24]. …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Structural origins of clustered protocadherin-mediated neuronal barcoding

Rubinstein¹,

Goodman²,

Maniatis³

et al. 2017

Seminars in Cell & Developmental Biology

Self Cite

View full text Add to dashboard Cite

Clustered protocadherins mediate neuronal self-recognition and non-self discrimination—neuronal “barcoding”—which underpin neuronal self-avoidance in vertebrate neurons. Recent structural, biophysical, computational, and cell-based studies on protocadherin structure and function have led to a compelling molecular model for the barcoding mechanism. Protocadherin isoforms assemble into promiscuous cis-dimeric recognition units and mediate cell-cell recognition through homophilic trans-interactions. Each recognition unit is composed of two arms extending from the membrane proximal EC6 domains. A cis-dimeric recognition unit with each arm coding adhesive trans homophilic specificity can generate a zipper-like assembly that in turn suggests a chain termination mechanism for self-vs-non-self-discrimination among vertebrate neurons.

show abstract

Section: Two Models Of the Pcdh Recognition Complex And Associatedmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Structural origins of clustered protocadherin-mediated neuronal barcoding

Rubinstein¹,

Goodman²,

Maniatis³

et al. 2017

Seminars in Cell & Developmental Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Whereas mature serotonergic neurons predominately express Pcdh α c2 (and Pcdh γ c3 and Pcdh γ c4 at lower levels) but not the alternate Pcdh isoforms, mature olfactory sensory neurons (OSNs) predominantly express alternate isoforms but not C-type isoforms (28). These cell type–specific patterns of expression correlate with the distinct axonal-arborization patterns of the two types of neurons.…”

Section: Discussionmentioning

confidence: 99%

Pcdhαc2 is required for axonal tiling and assembly of serotonergic circuitries in mice

Chen

Nwakeze

Denny

et al. 2017

Science

Self Cite

136

149

View full text Add to dashboard Cite

Serotonergic neurons project their axons pervasively throughout the brain and innervate various target fields in a space-filling manner, leading to tiled arrangements of their axon terminals to allow optimal allocation of serotonin among target neurons. Here we show that conditional deletion of the mouse protocadherin α (Pcdhα) gene cluster in serotonergic neurons disrupts local axonal tiling and global assembly of serotonergic circuitries and results in depression-like behaviors. Genetic dissection and expression profiling revealed that this role is specifically mediated by Pcdhαc2, which is the only Pcdhα isoform expressed in serotonergic neurons. We conclude that, in contrast to neurite self-avoidance, which requires single-cell identity mediated by Pcdh diversity, a single cell-type identity mediated by the common C-type Pcdh isoform is required for axonal tiling and assembly of serotonergic circuitries.

show abstract

Expression of protocadherin‐γC4 protein in the rat brain

Miralles

Taylor

Bear

et al. 2019

J of Comparative Neurology

View full text Add to dashboard Cite

It has been proposed that the combinatorial expression of γ‐protocadherins (Pcdh‐γs) and other clustered protocadherins (Pcdhs) provides a code of molecular identity and individuality to neurons, which plays a major role in the establishment of specific synaptic connectivity and formation of neuronal circuits. Particular attention has been directed to the Pcdh‐γ family, for which experimental evidence derived from Pcdh‐γ‐deficient mice shows that they are involved in dendrite self‐avoidance, synapse development, dendritic arborization, spine maturation, and prevention of apoptosis of some neurons. Moreover, a triple‐mutant mouse deficient in the three C‐type members of the Pcdh‐γ family (Pcdh‐γC3, Pcdh‐γC4, and Pcdh‐γC5) shows a phenotype similar to the mouse deficient in whole Pcdh‐γ family, indicating that the latter is largely due to the absence of C‐type Pcdh‐γs. The role of each individual C‐type Pcdh‐γ is not known. We have developed a specific antibody to Pcdh‐γC4 to reveal the expression of this protein in the rat brain. The results show that although Pcdh‐γC4 is expressed at higher levels in the embryo and earlier postnatal weeks, it is also expressed in the adult rat brain. Pcdh‐γC4 is expressed in both neurons and astrocytes. In the adult brain, the regional distribution of Pcdh‐γC4 immunoreactivity is similar to that of Pcdh‐γC4 mRNA, being highest in the olfactory bulb, dentate gyrus, and cerebellum. Pcdh‐γC4 forms puncta that are frequently apposed to glutamatergic and GABAergic synapses. They are also frequently associated with neuron‐astrocyte contacts. The results provide new insights into the cell recognition function of Pcdh‐γC4 in neurons and astrocytes.

show abstract

Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly

Cited by 148 publications

References 33 publications

Structural origins of clustered protocadherin-mediated neuronal barcoding

Structural origins of clustered protocadherin-mediated neuronal barcoding

Pcdhαc2 is required for axonal tiling and assembly of serotonergic circuitries in mice

Expression of protocadherin‐γC4 protein in the rat brain

Contact Info

Product

Resources

About