The ExDression Pattern of the Orphan Nuclear Receptor RORβ in the Developing and Adult Rat Nervous System Suggests a Role in the Processing of Sensory Information and in Circadian Rhythm

Schaeren-Wiemers, Nicole; André, Élisabeth; Kapfhammer, Josef P.; Becker‐André, Michael

doi:10.1111/j.1460-9568.1997.tb01698.x

Cited by 147 publications

(130 citation statements)

References 25 publications

(17 reference statements)

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“…We next examined the expression profile of Rorb in detail, as this protein is well known to be specifically expressed in L4 neurons of the mature neocortex (13,14). Interestingly, Rorb expression on E16.5 and E18.5 was mainly restricted to LCP neurons, as judged by almost no [on E16.5 ( Fig.…”

Section: Significancementioning

confidence: 99%

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Mutually repressive interaction between Brn1/2 and Rorb contributes to the establishment of neocortical layer 2/3 and layer 4

Oishi

Aramaki

Nakajima

2016

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

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Although several molecules have been shown to play important roles in subtype specification of neocortical neurons, the entire mechanism involved in the specification, in particular, of upper cortical plate (UCP) neurons still remains unclear. The UCP, which is responsible for intracortical connections in the neocortex, comprises histologically, functionally, and molecularly different layer 2/3 (L2/3) and L4. Here, we report the essential interactions between two types of transcription factors, Rorb (RAR-related orphan receptor beta) and Brn1/2 (Brain-1/Brain-2), for UCP specification. We found that Brn2 expression was detected in all upper layers in the immature UCP, but was subsequently restricted to L2/3, accompanied by up-regulation of Rorb in L4, suggesting demarcation of L2/3 and L4 during cortical maturation. Rorb indeed inhibited Brn2 expression and the expression of other L2/3 characteristics, revealed by ectopic expression and knockdown studies. Moreover, this inhibition occurred through direct binding of Rorb to the Brn2 locus. Conversely, Brn1/2 also inhibited Rorb expression and the expression of several L4 characteristics. Together, these results suggest that a mutually repressive mechanism exists between Brn1/2 and Rorb expression and that the established expression of Brn1/2 and Rorb further specifies those neurons into L2/3 and L4, respectively, during UCP maturation.cerebral cortex | cell fate | transcription factor | layer formation T he mammalian neocortex consists of six anatomically distinct layers, each of which contains one or more subtype of neurons, and is characterized by a specific cell morphology, birth date, molecular identity, and connectivity to other regions of the central nervous system. The cortical plate (CP) can be categorized into two populations: lower and upper cortical plate (LCP and UCP). Neurons in the LCP, which consists of layer 5 (L5) and L6, send axons to subcortical targets such as the thalamus, pons, and spinal cord, whereas the UCP, which is known to be much thicker in primates than in rodents, is characterized by corticocortical (intracortical) connections (1-3). The UCP, in rodents, can be further divided into L2/3 and L4. Many L2/3 neurons show a typical pyramidal morphology and send axons to the contralateral cortex, whereas L4 neurons, showing a round shape and granular morphology, receive inputs from the thalamus and transmit the thalamic inputs to local cortical networks (4). Thus, although UCP neurons share at least some features (e.g., intracortical connections), there are apparent differences (e.g., long vs. local projections and cell morphologies). However, how these differences arise during development is poorly understood.Previous studies have revealed the important roles of subtype-or lineage-specific transcription factors (TFs) in the specification of different neuronal subtypes (5-11). One of the intriguing features of how TFs specify neuronal subtypes is that a crucial TF for a given subtype sometimes suppresses other subtypes (3,12). This mechan...

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Section: Significancementioning

confidence: 99%

“…Rorb belongs to the orphan nuclear receptor family and is preferentially expressed in L4 of the mature neocortex (13,14). Brn1/2 are members of the class III POU (Pit1-Oct1/Oct2-UNC86) domain transcription factors and are preferentially expressed in L2/3 and L5 of the mature neocortex (15-17).…”

mentioning

confidence: 99%

Mutually repressive interaction between Brn1/2 and Rorb contributes to the establishment of neocortical layer 2/3 and layer 4

Oishi

Aramaki

Nakajima

2016

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

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“…Levels of RORβ mRNA were determined by competitive RT-PCR and normalized to total RNA. published in situ hybridization data (Schaeren-Wiemers et al, 1997).…”

Section: Generation Of Transgenic Mice Carrying Rorβ Null Allelesmentioning

confidence: 99%

Disruption of retinoid-related orphan receptor β changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice

André¹,

Conquet²,

Steinmayr³

et al. 1998

EMBO J

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The orphan nuclear receptor RORβ is expressed in areas of the central nervous system which are involved in the processing of sensory information, including spinal cord, thalamus and sensory cerebellar cortices. Additionally, RORβ localizes to the three principal anatomical components of the mammalian timing system, the suprachiasmatic nuclei, the retina and the pineal gland. RORβ mRNA levels oscillate in retina and pineal gland with a circadian rhythm that persists in constant darkness. RORβ -/-mice display a ducklike gait, transient male incapability to sexually reproduce, and a severely disorganized retina that suffers from postnatal degeneration. Consequently, adult RORβ -/-mice are blind, yet their circadian activity rhythm is still entrained by light-dark cycles. Interestingly, under conditions of constant darkness, RORβ -/-mice display an extended period of free-running rhythmicity. The overall behavioral phenotype of RORβ -/-mice, together with the chromosomal localization of the RORβ gene, suggests a close relationship to the spontaneous mouse mutation vacillans described Ͼ40 years ago.

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“…Rorb is expressed in all neural retina layers from early stages with a peak at neonatal stages, suggestive of a role in many differentiating retinal cell types including both cones and rods (21)(22)(23). We previously reported that Rorb and Crx synergistically induce the S opsin promoter (24), indicating a role for Rorb in cone differentiation.…”

mentioning

confidence: 94%

Retinoid-related orphan nuclear receptor RORβ is an early-acting factor in rod photoreceptor development

et al. 2009

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

113

105

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Rods and cones are morphologically and developmentally distinct photoreceptor types with different functions in vision. Cones mediate daylight and color vision and in most mammals express M and S opsin photopigments for sensitivity to medium-long and short light wavelengths, respectively. Rods mediate dim light vision and express rhodopsin photopigment. The transcription factor networks that direct differentiation of each photoreceptor type are incompletely defined. Here, we report that Rorb ؊/؊ mice lacking retinoid-related orphan nuclear receptor ␤ lose rods but overproduce primitive S cones that lack outer segments. The phenotype reflects pronounced plasticity between rod and cone lineages and resembles that described for Nrl ؊/؊ mice lacking neural retina leucine zipper factor. Rorb ؊/؊ mice lack Nrl expression and reexpression of Nrl in Rorb ؊/؊ mice converts cones to rod-like cells. Thus, Rorb directs rod development and does so at least in part by inducing the Nrl-mediated pathway of rod differentiation.cone ͉ differentiation R ods and cones are distinct receptor cell types that mediate dim and bright light vision, respectively. In the mouse, cones are generated between midgestation and birth (1) and subpopulations differentially express M and S opsin photopigments for sensitivity to medium-long and short light wavelengths, respectively (2). Rods express rhodopsin and greatly outnumber cones in mice. Rod generation lags behind that of cones and is more protracted, lasting until about a week after birth. Rods, cones, and other retinal cell types are generated in a stereotypical order from multipotent progenitors, and it has been proposed that a combination of transcription factor activities and external signals at a given developmental stage prompts progenitors to enter specific differentiation pathways (3, 4).The transcription factors that direct the generation of rod and cone precursors and the terminal differentiation of these cell types are incompletely defined. During terminal differentiation of cones, thyroid hormone receptor TR␤2 is required for M opsin induction such that without TR␤2, cones express only S opsin (5). Factors that promote rod differentiation and survival include leucine zipper protein Nrl (6), orphan nuclear receptor Nr2e3 (7, 8), homeodomain proteins Crx and Otx2 (9-11), and retinoblastoma protein Rb (12,13). Nrl induces Nr2e3 expression and these two genes define a transcriptional hierarchy for rod differentiation. Nrl Ϫ/Ϫ mice overproduce S cones at the expense of rods (6) whereas ectopic Nrl expression converts cones to rods (14). Nr2e3 deficiency causes an enhanced cone phenotype and misexpression of cone genes in rods, suggesting that Nr2e3 represses cone genes to maintain the rod phenotype (15-19). Human NRL and NR2E3 mutations result in retinopathy phenotypes (8,20). The above findings suggest that rod and cone precursors share a default differentiation program as cones and that rod differentiation requires the action of additional transcription factors.The Rorb gene encodin...

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The ExDression Pattern of the Orphan Nuclear Receptor RORβ in the Developing and Adult Rat Nervous System Suggests a Role in the Processing of Sensory Information and in Circadian Rhythm

Cited by 147 publications

References 25 publications

Mutually repressive interaction between Brn1/2 and Rorb contributes to the establishment of neocortical layer 2/3 and layer 4

Mutually repressive interaction between Brn1/2 and Rorb contributes to the establishment of neocortical layer 2/3 and layer 4

Disruption of retinoid-related orphan receptor β changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice

Retinoid-related orphan nuclear receptor RORβ is an early-acting factor in rod photoreceptor development

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