Down‐regulation of protocadherin‐α A isoforms in mice changes contextual fear conditioning and spatial working memory

Fukuda, Emi; Hamada, Shin; Hasegawa, Sonoko; Katori, Shota; Sanbo, Makoto; Miyakawa, Tsuyoshi; Yamamoto, Toshiyuki; Yamamoto, Hiroyuki; Hirabayashi, Takahiro; Yagi, Takeshi

doi:10.1111/j.1460-9568.2008.06428.x

Cited by 63 publications

(58 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3) is denoted by a pair of protocadherin genes (PCDHA1 and PCDHB4), which establish and maintain specific neuronal connections and have implications for synaptic specificity, serotonergic innervation of the brain, and fear conditioning (43). PCDHB4 was also identified in the d N /d S analyses.…”

Section: Resultsmentioning

confidence: 99%

Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

Montague

Gandolfi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

285

269

View full text Add to dashboard Cite

Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.Felis catus | domestication | genome T he domestic cat (Felis silvestris catus) is a popular pet species, with as many as 600 million individuals worldwide (1). Cats and other members of Carnivora last shared a common ancestor with humans ∼92 million years ago (2, 3). The cat family Felidae includes ∼38 species that are widely distributed across the world, inhabiting diverse ecological niches that have resulted in divergent morphological and behavioral adaptations (4). The earliest archaeological evidence for human coexistence with cats dates to ∼9.5 kya in Cyprus and ∼5 kya in central China (5, 6), during periods when human populations adopted more agricultural lifestyles. Given their sustained beneficial role surrounding vermin control since the human transition to agriculture, any selective forces acting on cats may have been minimal subsequent to their domestication. Unlike many other domesticated mammals bred for food, herding, hunting, or security, most of the 30-40 cat breeds originated recently, within the past 150 y, largely due to selection for aesthetic rather than functional traits.Previous studies have assessed breed differentiation (6, 7), phylogenetic origins of the domestic cat (8), and the extent of recent introgression between domestic cats and wildcats (9, 10). However, little is known regarding the impact of the domestication process within the genomes of modern cats and how this compares with genetic changes accompanying selection identified...

show abstract

Section: Resultsmentioning

confidence: 99%

Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

Montague

Gandolfi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

285

269

View full text Add to dashboard Cite

show abstract

“…Recent studies on Pcdh␣ knockout mice show that Pcdh␣ is involved in the axonal coalescence of olfactory neurons into glomeruli (117), and in serotonergic projections (159). Moreover, downregulation of Pcdh␣ isoforms leads to learning abnormalities (99). On the other hand, the molecular properties of Pcdh␣ are not fully understood.…”

Section: Clustered Protocadherins: Protocadherin ␣ ␤ and ␥mentioning

confidence: 99%

Cadherins in Brain Morphogenesis and Wiring

Hirano

Takeichi

2012

Physiological Reviews

274

312

View full text Add to dashboard Cite

LHirano S, Takeichi M. Cadherins in Brain Morphogenesis and Wiring. Physiol Rev 92: 597-634, 2012; doi:10.1152/physrev.00014.2011 -dependent cell-cell adhesion molecules that play critical roles in animal morphogenesis. Various cadherin-related molecules have also been identified, which show diverse functions, not only for the regulation of cell adhesion but also for that of cell proliferation and planar cell polarity. During the past decade, understanding of the roles of these molecules in the nervous system has significantly progressed. They are important not only for the development of the nervous system but also for its functions and, in turn, for neural disorders. In this review, we discuss the roles of cadherins and related molecules in neural development and function in the vertebrate brain.

show abstract

“…The amounts of monoamines and their metabolites were measured using HPLC with electrochemical detection (described by Fukuda et al, 2008). Mice were killed by decapitation at 10 weeks of age, and the brain regions were rapidly dissected out and frozen at Ϫ80°C, until assayed.…”

Section: Measurement Of Monoamines By High Performance Liquid Chromatmentioning

confidence: 99%

Protocadherin-α Family Is Required for Serotonergic Projections to Appropriately Innervate Target Brain Areas

Katori¹,

Hamada²,

Noguchi³

et al. 2009

J. Neurosci.

152

160

View full text Add to dashboard Cite

Serotonergic axons from the raphe nuclei in the brainstem project to every region of the brain, where they make connections through their extensive terminal arborizations. This serotonergic innervation contributes to various normal behaviors and psychiatric disorders. The protocadherin-␣ (Pcdha) family of clustered protocadherins consists of 14 cadherin-related molecules generated from a single gene cluster. We found that the Pcdhas were strongly expressed in the serotonergic neurons. To elucidate their roles, we examined serotonergic fibers in a mouse mutant (Pcdha ⌬CR/⌬CR ) lacking the Pcdha cytoplasmic region-encoding exons, which are common to the gene cluster. In the first week after birth, the distribution pattern of serotonergic fibers in Pcdha ⌬CR/⌬CR mice was similar to wild-type, but by 3 weeks of age, when the serotonergic axonal termini complete their arborizations, the distribution of the projections was abnormal. In some target regions, notably the globus pallidus and substantia nigra, the normally even distribution of serotonin axonal terminals was, in the mutants, dense at the periphery of each region, but sparse in the center. In the stratum lacunosum-moleculare of the hippocampus, the mutants showed denser serotonergic innervation than in wild-type, and in the dentate gyrus of the hippocampus and the caudateputamen, the innervation was sparser. Together, the abnormalities suggested that Pcdha proteins are important in the late-stage maturation of serotonergic projections. Further examination of alternatively spliced exons encoding the cytoplasmic tail showed that the A-type (but not the B-type) cytoplasmic tail was essential for the normal development of serotonergic projections.

show abstract

Down‐regulation of protocadherin‐α A isoforms in mice changes contextual fear conditioning and spatial working memory

Cited by 63 publications

References 39 publications

Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

Cadherins in Brain Morphogenesis and Wiring

Protocadherin-α Family Is Required for Serotonergic Projections to Appropriately Innervate Target Brain Areas

Contact Info

Product

Resources

About