The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex

Larsen, Rachel A.; Proue, Alatheia; Christiansen, Matthew; Nakagawa, Yasushi

doi:10.1101/272427

Cited by 6 publications

(7 citation statements)

References 89 publications

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“…18a). Consistent with previous findings in humans 21 and mice 24 , whole-mount and serial tissue section in situ hybridization revealed that Cyp26b1 is upregulated in the prospective motor cortex (MOs and MOp) and anterior insula compared to the mPFC and OFC, defined by high expression of Cbln2, and SSp, defined by Rorb (Fig. 5a, b, Extended Data Fig.…”

Section: Articlesupporting

confidence: 91%

“…RA signalling has previously been shown to be involved in the regulation of proliferation, cell cycle timing and cortical laminar development [22][23][24] , which could underlie our findings. Thus, we assessed whether the constitutive deletion of Rarb and Rxrg leads to changes in cortical size and laminar organization.…”

Section: Articlesupporting

confidence: 68%

“…RA is a diffusible biologically active derivative of vitamin A that is involved in neural tube patterning, neurogenesis, cell differentiation and synaptic function 12,13,[22][23][24][25][26][27] . Moreover, alterations in RA signalling have been implicated in the pathophysiology of ASD [28][29][30] and SCZ 14,31,32 .…”

Section: Mid-fetal Pfc-enriched Gradient Of Ramentioning

confidence: 99%

“…18b). Although mice with constitutive deletion of Cyp26b1 died perinatally, it has previously been shown that genetic deletion of Cyp26b1 in mice resulted in the expansion of RA signalling in multiple organs prenatally 38 and post-natally in the mouse mPFC 24 . To investigate the possible role of CYP26B1 in restricting RA signalling to the mouse medial frontal cortex, we generated Cyp26b1 KO mice that also contained the RARE-lacZ transgene.…”

Section: Articlementioning

confidence: 99%

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Regulation of prefrontal patterning and connectivity by retinoic acid

Shibata

Pattabiraman

Lorente-Galdós

et al. 2021

Nature

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The prefrontal cortex (PFC) and its connections with the mediodorsal thalamus are crucial for cognitive flexibility and working memory 1 and are thought to be altered in disorders such as autism 2,3 and schizophrenia 4,5 . Although developmental mechanisms that govern the regional patterning of the cerebral cortex have been characterized in rodents [6][7][8][9] , the mechanisms that underlie the development of PFCmediodorsal thalamus connectivity and the lateral expansion of the PFC with a distinct granular layer 4 in primates 10,11 remain unknown. Here we report an anterior (frontal) to posterior (temporal), PFC-enriched gradient of retinoic acid, a signalling molecule that regulates neural development and function [12][13][14][15] , and we identify genes that are regulated by retinoic acid in the neocortex of humans and macaques at the early and middle stages of fetal development. We observed several potential sources of retinoic acid, including the expression and cortical expansion of retinoic-acid-synthesizing enzymes specifically in primates as compared to mice. Furthermore, retinoic acid signalling is largely confined to the prospective PFC by CYP26B1, a retinoic-acid-catabolizing enzyme, which is upregulated in the prospective motor cortex. Genetic deletions in mice revealed that retinoic acid signalling through the retinoic acid receptors RXRG and RARB, as well as CYP26B1-dependent catabolism, are involved in proper molecular patterning of prefrontal and motor areas, development of PFC-mediodorsal thalamus connectivity, intra-PFC dendritic spinogenesis and expression of the layer 4 marker RORB. Together, these findings show that retinoic acid signalling has a critical role in the development of the PFC and, potentially, in its evolutionary expansion.The PFC reaches its greatest complexity in anthropoid primates (monkeys and apes), which appear to uniquely have many prefrontal areas that cover the entire anterior two-thirds of the frontal lobe and a well-defined granular layer 4 10,11 . Previous analyses revealed that the transcriptomic differences between neocortical areas are most prominent in primates during the middle stages of fetal development, corresponding to post-conception weeks (PCW) 13 to 24 (hereafter referred to as 'mid-fetal') 16,17 -a crucial period for neuronal specification and the initial assembly of neocortical neural circuits 18 . Thus, we hypothesized that the molecular processes that govern the development and evolutionary diversification of the PFC could be revealed by differential regional gene expression analysis of the primate mid-fetal neocortex. Fetal frontal upregulation of RA-related genesUsing human BrainSpan RNA-sequencing (RNA-seq) data 17 , we screened for genes that are differentially upregulated in the mid-fetal frontal lobe. The mid-fetal data consisted of tissue-level samples ranging in age from PCW 16 to 22, which included four prospective PFC areas (medial, mPFC or MFC; orbital, oPFC or OFC; dorsolateral, dlPFC or DFC; and ventrolateral, vlPFC or VFC) and the primar...

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Section: Articlesupporting

confidence: 91%

Section: Articlesupporting

confidence: 68%

Section: Mid-fetal Pfc-enriched Gradient Of Ramentioning

confidence: 99%

Section: Articlementioning

confidence: 99%

See 2 more Smart Citations

Regulation of prefrontal patterning and connectivity by retinoic acid

Shibata

Pattabiraman

Lorente-Galdós

et al. 2021

Nature

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“…Anxiety symptoms are common in schizophrenia patients [40,41]. Cyp26b1 is is expressed in parvalbumin-positive interneurons [42]. Most interestingly, knockdown Cyp26b1 in the nucleus accumbens shell decreased anxiety-like behavior [43].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of open field behavior in outbred heterogeneous stock rats identifies multiple loci implicated in psychiatric disorders

Gunturkun

Wang

Chitre

et al. 2021

Preprint

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Many personality traits are influenced by genetic factors. Rodents models provide an efficient system for analyzing genetic contribution to these traits. Using 1,246 adolescent heterogeneous stock (HS) male and female rats, we conducted a genome-wide association study (GWAS) of behaviors measured in an open field, including locomotion, novel object interaction, and social interaction. We identified 30 genome-wide significant quantitative trait loci (QTL). Using multiple criteria, including the presence of high impact genomic variants and co-localization of cis-eQTL, we identified 13 candidate genes (Adarb2, Ankrd26, Cacna1c, Clock, Crhr1, Ctu2, Cyp26b1, Eva1a, Fam114a1, Kcnj9, Mlf2, Rab27b, Sec11a) for these traits. Most of these genes have been implicated by human GWAS of various psychiatric traits. For example, Cacna1c, a gene known to be critical for social behavior in rodents and implicated in human schizophrenia and bipolar disorder, is a candidate gene for distance to the social zone. In addition, the QTL region for total distance to the novel object zone, on Chr1 at 144 Mb, is syntenic to a hotspot on human Chr15 (82.5-90.8 Mb) that contains 14 genes associated with psychiatric or substance abuse traits. Although some of the genes identified by this study appear to replicate findings from prior human GWAS, others likely represent novel findings that can be the catalyst for future molecular and genetic insights into human psychiatric diseases. Together, these findings provide strong support for the use of the HS population to study psychiatric disorders.

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Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior

et al. 2022

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Cortical neural circuits are complex but very precise networks of balanced excitation and inhibition. Yet, the molecular and cellular mechanisms that form the balance are just beginning to emerge. Here, using conditional γ-aminobutyric acid receptor B1- deficient mice we identify a γ-aminobutyric acid/tumor necrosis factor superfamily member 12-mediated bidirectional communication pathway between parvalbumin-positive fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing medial prefrontal cortex. Interruption of the GABAergic signaling to oligodendrocyte precursor cells results in reduced myelination and hypoactivity of interneurons, strong changes of cortical network activities and impaired social cognitive behavior. In conclusion, glial transmitter receptors are pivotal elements in finetuning distinct brain functions.

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The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex

Cited by 6 publications

References 89 publications

Regulation of prefrontal patterning and connectivity by retinoic acid

Regulation of prefrontal patterning and connectivity by retinoic acid

Genome-wide association study of open field behavior in outbred heterogeneous stock rats identifies multiple loci implicated in psychiatric disorders

Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior

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