Wnt5a regulates ventral midbrain morphogenesis and the development of A9-A10 dopaminergic cells in vivo.
Andersson ER, Prakash N, Cajanek L, Minina E, Bryja V, Bryjova L, Yamaguchi TP, Hall AC, Wurst W, Arenas E
Wnt5a helps shape the midbrain and guide the development of dopamine-producing brain cells, including those involving the NR4A2 gene. In mice without Wnt5a, dopamine cell precursors form too early and fail to mature properly, leading to brain shape defects and temporary changes in neuron numbers.
- Wnt5a controls brain cell shape and positioning during development
- Wnt5a regulates NR4A2+ dopamine cell precursors
- Loss of Wnt5a causes delayed dopamine neuron maturation
- Wnt5a deficiency disrupts midbrain structure and cell alignment
- Wnt5a acts through the PCP pathway to guide brain development
Inhibition of adipocyte differentiation by Nur77, Nurr1, and Nor1.
Chao LC, Bensinger SJ, Villanueva CJ, Wroblewski K, Tontonoz P
NR4A2 (Nurr1) and related proteins block fat cell formation in laboratory models, likely by interfering with early steps in fat cell development and by activating genes that prevent differentiation. This suggests that NR4A2 activity may naturally limit fat accumulation, which could be relevant to metabolic issues in NR4A2-related syndrome.
- NR4A2/Nurr1 blocks fat cell development in lab models
- It acts early by stopping cell division needed for fat formation
- NR4A2 affects genes linked to cell communication and structure
- Its activity is boosted by inflammation and fasting
- Overcoming this block is not possible with standard fat cell signals
Repeated developmental exposure to chlorpyrifos and methyl parathion causes persistent alterations in nicotinic acetylcholine subunit mRNA expression with chlorpyrifos altering dopamine metabolite levels.
Eells JB, Brown T
Exposure to the pesticide chlorpyrifos during early development alters dopamine metabolism and nicotinic receptor expression in the brain, with effects lasting into adulthood. Methyl parathion also changed receptor expression, but did not affect dopamine levels.
- Chlorpyrifos increased dopamine breakdown markers in young rats
- Changes in brain receptor levels persisted into adulthood
- Both pesticides altered nicotinic receptor subunits in dopamine-related brain areas
- No changes in key dopamine gene regulators were found
- Effects were seen even after stopping exposure for weeks
Chemically defined sequential culture media for TH+ cell derivation from human embryonic stem cells.
Song T, Chen G, Wang Y, Mao G, Wang Y, Bai H
This study developed a reliable method to grow large numbers of dopamine-producing brain cells from human stem cells, which can release dopamine and improve symptoms in Parkinson's disease model rats. These cells show key markers of midbrain dopamine neurons and function similarly to natural ones.
- Produces over 90% dopamine-producing cells from stem cells
- Cells release dopamine when stimulated
- Cells survive and reduce symptoms in Parkinson's rats
- Uses a defined, consistent culture system
- Potential for future Parkinson's cell therapy
Target identification for CNS diseases by transcriptional profiling.
Altar CA, Vawter MP, Ginsberg SD
This review identifies key genes and pathways involved in brain disorders like Alzheimer's, Parkinson's, schizophrenia, and depression, highlighting targets related to neurotrophins, dopamine signaling, synaptic function, and oxidative stress that could lead to new treatments.
- NR4A2 (Nurr-1) is a key target in Parkinson's disease pathways
- Dopamine and neurotrophic signaling are central to brain health
- Antioxidant and synaptic repair pathways may help aging-related decline
- Gene changes in depression and schizophrenia point to treatable biological mechanisms
- Drug effects on brain gene expression reveal promising therapeutic targets
Expression of dopamine-associated genes on conjunctiva stromal-derived human mesenchymal stem cells.
Nadri S, Soleimani M, Mobarra Z, Amini S
Conjunctiva-derived stem cells can be turned into dopamine-producing cells, which may offer a new source for treating Parkinson's disease and other brain disorders involving dopamine loss.
- Stem cells from eye tissue become dopamine-making cells
- They express key genes and proteins needed for dopamine production
- Higher cell passage levels increase dopamine-related protein levels
- These cells could potentially be used in brain disease therapies
mRNA expression of the Nurr1 and NGFI-B nuclear receptor families following acute and chronic administration of methamphetamine.
Akiyama K, Isao T, Ide S, Ishikawa M, Saito A
Methamphetamine exposure increases Nurr1 and NGFI-B mRNA levels in key brain regions involved in movement, reward, and cognition, with lasting changes after repeated use. These changes suggest that NR4A2 (Nurr1) and related genes may be disrupted in ways relevant to neurodevelopmental and psychiatric conditions.
- Methamphetamine raises Nurr1 and NGFI-B mRNA in brain areas linked to behavior and movement
- Chronic meth use leads to long-term changes in gene expression in the brain
- The brain's ability to respond to meth changes after repeated exposure
- These genes are involved in pathways that may be relevant to NR4A2-related syndrome
- Findings may inform future treatments targeting gene regulation
Alterations in amphetamine-stimulated dopamine overflow due to the Nurr1-null heterozygous genotype and postweaning isolation.
Moore TM, Brown T, Cade M, Eells JB
A single missing copy of the NR4A2 gene (Nurr1) combined with early-life isolation stress causes major disruptions in dopamine signaling in the brain's reward pathway, which may increase the risk for disorders like schizophrenia or ADHD. This effect is not seen with either factor alone, showing how genes and environment interact to affect brain function.
- One missing NR4A2 gene copy alters dopamine in the reward center
- Isolation after weaning worsens dopamine problems in genetically vulnerable mice
- Combined genetic and environmental stress causes big changes in dopamine release
- This interaction may explain some cases of schizophrenia or ADHD
- The findings highlight the importance of early-life environment for gene-related brain disorders
Anterior-posterior graded response to Otx2 controls proliferation and differentiation of dopaminergic progenitors in the ventral mesencephalon.
Omodei D, Acampora D, Mancuso P, Prakash N, Di Giovannantonio LG, Wurst W, Simeone A
Otx2 controls the growth and development of dopamine-producing brain cells in the midbrain by regulating how progenitor cells divide and turn into mature neurons. This effect varies along the front-to-back axis of the brain, with higher Otx2 levels boosting cell production and lower levels causing premature maturation and reduced development.
- Otx2 regulates dopamine neuron development in the midbrain
- Otx2 levels control how long progenitor cells keep dividing
- Low Otx2 leads to early maturation and fewer dopamine neurons
- Otx2 acts in a front-to-back gradient across the midbrain
- This process could inform stem cell therapies for Parkinson’s
Analysis of area-specific expression patterns of RORbeta, ER81 and Nurr1 mRNAs in rat neocortex by double in situ hybridization and cortical box method.
Hirokawa J, Watakabe A, Ohsawa S, Yamamori T
This study mapped the expression of three genes—Nurr1, ER81, and RORbeta—in the rat neocortex and found that their patterns align with brain areas and functional hierarchy. The findings suggest that these genes help define distinct cortical regions and may reflect how brain areas process information. The method used allows precise comparison across brain regions and individuals.
- Nurr1, ER81, and RORbeta have distinct, complementary patterns in the rat cortex
- Their expression matches known brain area boundaries and functional levels
- Nurr1 and ER81 are not coexpressed, but RORbeta and ER81 are in some layer 5 neurons
- Gene expression profiles correlate with cortical processing hierarchy
- The method enables statistical analysis of gene patterns across brain regions
Identification of a novel nurr1-interacting protein.
Luo Y, Xing F, Guiliano R, Federoff HJ
A new protein called NuIP binds to and boosts the activity of Nurr1, a key protein for dopamine neuron development. This interaction enhances Nurr1's ability to turn on genes important for dopamine function and neuron health, and reducing NuIP weakens these effects.
- NuIP boosts Nurr1 activity in dopamine neurons
- NuIP helps control genes needed for dopamine production
- Lower NuIP levels reduce neuron function and gene expression
- NuIP and Nurr1 are found together in adult brain dopamine cells
- This interaction may affect how dopamine neurons develop and survive
NR4A2 controls the differentiation of selective dopaminergic nuclei in the zebrafish brain.
Blin M, Norton W, Bally-Cuif L, Vernier P
NR4A2 is essential for the development of specific dopamine-producing brain cells in zebrafish, and its reduction leads to lifelong hyperactivity, mirroring symptoms seen in humans with NR4A2-related disorders.
- NR4A2 controls dopamine neuron development in zebrafish brain regions
- Loss of NR4A2 causes persistent hyperactivity
- NR4A2 guides dopamine cell maturation, not just enzyme production
- Zebrafish model closely reflects human NR4A2 syndrome features
- Findings support NR4A2's role in motor control and brain development
FGF-8 stimulates the expression of NR4A orphan nuclear receptors in osteoblasts.
Lammi J, Aarnisalo P
FGF-8b boosts the activity of NR4A nuclear receptors in bone-forming cells, which helps drive their growth. These receptors, including Nurr1, are involved in how FGF-8b promotes bone cell development.
- FGF-8b increases NR4A receptor levels in bone cells
- NR4A receptors help mediate FGF-8b’s growth effects
- Nurr1 and NGFI-B support bone cell proliferation
- Signaling pathways like MAPK and PI-3K are involved
- Findings may inform bone development and repair
Decreased NURR1 gene expression in patients with Parkinson's disease.
Le W, Pan T, Huang M, Xu P, Xie W, Zhu W, Zhang X, Deng H, Jankovic J
People with Parkinson's disease have lower levels of NURR1 gene expression in blood cells, especially those with a family history of the disease, suggesting a possible systemic link to the condition. This finding may help identify individuals at higher risk and could inform future treatments targeting NURR1.
- NURR1 levels are lower in Parkinson’s patients’ blood cells
- Low NURR1 is linked to higher Parkinson’s risk in women and older adults
- NURR1 reduction is seen even without medication
- Blood NURR1 levels may serve as a biomarker for Parkinson’s
- Suggests systemic involvement beyond the brain
Effect of the co-administration of vitamin C and vitamin E on tyrosine hydroxylase and Nurr1 expression in the prenatal rat ventral mesencephalon.
Lee HY, Naha N, Ullah N, Jin GZ, Kong IK, Koh PO, Seong HH, Kim MO
Vitamin C and vitamin E together boost the levels of tyrosine hydroxylase and Nurr1 in developing rat brain cells, with vitamin E enhancing vitamin C's effect. This suggests a potential benefit for early intervention in conditions involving dopamine neuron loss, such as Parkinsonism.
- Vitamins C and E together increase dopamine-related proteins
- Vitamin C alone boosts tyrosine hydroxylase
- Both vitamins raise Nurr1 levels individually
- Vitamin E enhances vitamin C's effect synergistically
- Findings may inform early treatment strategies for dopamine disorders
Expression of the LRRK2 gene in the midbrain dopaminergic neurons of the substantia nigra.
Han BS, Iacovitti L, Katano T, Hattori N, Seol W, Kim KS
LRRK2 is highly expressed in the A9 midbrain dopaminergic neurons of the substantia nigra, the same neurons lost in Parkinson's disease, suggesting LRRK2 dysfunction may directly contribute to their degeneration. This finding highlights LRRK2's potential role in the selective vulnerability of these neurons.
- LRRK2 is expressed in A9 neurons, which are lost in Parkinson's disease
- LRRK2 is also found in surrounding non-dopaminergic cells
- LRRK2 levels are higher in the substantia nigra than in other dopamine regions
- Mutant LRRK2 may directly cause A9 neuron degeneration
- This supports LRRK2 as a key player in Parkinson's disease pathology
Nr4a2 is essential for the differentiation of dopaminergic neurons during zebrafish embryogenesis.
Luo GR, Chen Y, Li XP, Liu TX, Le WD
Nr4a2 is crucial for turning dopamine-producing brain cells into mature, functional neurons during early zebrafish development, not for keeping the precursor cells alive. Without Nr4a2, fewer dopamine neurons form and they produce less dopamine, but the precursor cells actually increase in number. Restoring Nr4a2 with mouse mRNA can fix these problems.
- Nr4a2 drives dopamine neuron maturation, not survival
- Lack of Nr4a2 reduces dopamine neurons and dopamine levels
- Precursor cells increase when Nr4a2 is missing
- Mouse Nr4a2 mRNA can rescue the defects
- Zebrafish model shows Nr4a2's role in early brain development
Orphan nuclear receptor NR4A2 expressed in T cells from multiple sclerosis mediates production of inflammatory cytokines.
Doi Y, Oki S, Ozawa T, Hohjoh H, Miyake S, Yamamura T
NR4A2 is a key driver of inflammation in multiple sclerosis by boosting the production of harmful cytokines in immune cells. Blocking NR4A2 reduces inflammation and disease severity in animal models, suggesting it could be a promising treatment target.
- NR4A2 is overactive in immune cells from MS patients
- It increases production of inflammatory cytokines IL-17 and IFN-gamma
- Reducing NR4A2 activity lowers inflammation and disease in models
- NR4A2 may be a treatable target for MS
- Findings are directly relevant to immune-driven neurological disease
Expression of functional dopaminergic phenotype in purified cultured Müller cells from vertebrate retina.
Kubrusly RC, Panizzutti R, Gardino PF, Stutz B, Reis RA, Ventura AL, de Mello MC, de Mello FG
Müller cells, a type of retinal glial cell, can produce and release dopamine in culture, showing neuron-like dopaminergic behavior even without nerve input. This includes making dopamine from precursor molecules, releasing it through a transporter, and activating dopamine receptors, with Nurr1 expression supporting these traits.
- Müller cells make and release dopamine in culture
- They express key dopaminergic proteins like DDC and DAT
- Dopamine release is transporter-dependent and functional
- Nurr1 is present, linking to dopaminergic identity
- Dopamine production increases with cAMP signals
Nurr1 transcriptionally regulates the expression of alpha-synuclein.
Yang YX, Latchman DS
Nurr1 reduces the production of alpha-synuclein, and when Nurr1 levels are low—such as in people with NR4A2-related syndrome—alpha-synuclein increases, which may contribute to neurological problems. This suggests that boosting Nurr1 activity could help lower harmful alpha-synuclein levels.
- Low Nurr1 increases alpha-synuclein production
- Nurr1 normally suppresses alpha-synuclein
- NR4A2 mutations may raise alpha-synuclein
- Targeting Nurr1 could be a treatment strategy
Anabolic effects of PTH in cyclooxygenase-2 knockout osteoblasts in vitro.
Choudhary S, Huang H, Raisz L, Pilbeam C
In lab studies, blocking COX-2 activity allowed PTH to strongly boost bone cell development and mineralization, suggesting that natural prostaglandins normally suppress PTH's bone-building effects. This effect appears linked to improved cAMP signaling and increased expression of the NR4A2 gene.
- COX-2 inhibition enhances PTH's bone-building effects in lab-grown cells
- NR4A2 gene expression increases in response to PTH when COX-2 is blocked
- PTH boosts bone cell maturation and mineralization without COX-2
- cAMP signaling is more effective when COX-2 is absent
- Prostaglandins normally dampen PTH's anabolic response
Nurr1 deficiency predisposes to lactacystin-induced dopaminergic neuron injury in vitro and in vivo.
Pan T, Zhu W, Zhao H, Deng H, Xie W, Jankovic J, Le W
Lower levels of the Nurr1 protein make dopamine-producing brain cells more vulnerable to damage from toxins that impair the cell's waste disposal system, both in lab tests and in mice. This suggests that people with NR4A2-related syndrome may be more sensitive to environmental factors that harm brain cells.
- Nurr1 deficiency increases risk of dopamine neuron damage
- Toxins blocking protein recycling harm Nurr1-lacking cells more
- Mice with low Nurr1 lose more dopamine neurons after toxin exposure
- Nurr1 helps protect brain cells from stress and death
- This may explain why some people with NR4A2 mutations develop symptoms
Comparative analysis of transcriptional profiling of CD3+, CD4+ and CD8+ T cells identifies novel immune response players in T-cell activation.
Wang M, Windgassen D, Papoutsakis ET
This study analyzed gene activity in different types of T cells and found new genes involved in immune responses, including NR4A2, which may play a role in communication between immune cells. The findings reveal unexpected genes and pathways active during T-cell activation, some of which could be relevant to immune-related conditions.
- NR4A2 is identified as a potential player in T-cell communication
- New genes linked to T-cell activation and immune function were discovered
- Some genes previously unknown in T-cell activation are now implicated
- Findings may help understand immune system regulation and dysfunction
Extracellular signal-regulated kinases (ERK) and protein kinase C (PKC) activities are involved in the modulation of Nur77 and Nor-1 expression by dopaminergic drugs.
Bourhis E, Maheux J, Rouillard C, Lévesque D
Dopamine drugs affect the expression of two brain genes, Nur77 and Nor-1, through specific signaling pathways involving MEK and PKC enzymes. These pathways differ between the two genes and are linked to changes in movement behavior, suggesting they play distinct roles in how the brain responds to dopamine-related drugs.
- Dopamine drugs change Nur77 and Nor-1 gene levels via MEK and PKC pathways
- MEK and PKC are key for Nur77, but only PKC affects Nor-1
- Drug-induced movement changes match Nur77 changes, not Nor-1
- These pathways may influence how the brain responds to psychiatric medications
- Understanding these signals helps explain dopamine system function
Preliminary evidence for a modulation of fetal dopaminergic development by maternal immune activation during pregnancy.
Meyer U, Engler A, Weber L, Schedlowski M, Feldon J
Maternal immune activation during pregnancy can alter the development of the fetal dopamine system, increasing dopamine neurons and changing key genes involved in their formation. This may help explain how prenatal infections raise the risk of schizophrenia and autism in offspring.
- Prenatal immune activation increases fetal dopamine neurons
- Changes in genes like Nurr1 and Shh affect dopamine development
- This may underlie increased risk for schizophrenia and autism
- Findings suggest immune exposure disrupts early brain development
- Supports need for further study on neurodevelopmental impacts
Alpha-chemokines regulate proliferation, neurogenesis, and dopaminergic differentiation of ventral midbrain precursors and neurospheres.
Edman LC, Mira H, Erices A, Malmersjö S, Andersson E, Uhlén P, Arenas E
Alpha-chemokines boost the production of dopamine-producing neurons from brain precursor cells, which could help develop cell therapies for Parkinson's disease and may offer insights into treating NR4A2-related disorders involving dopamine neuron development.
- CXCL6 promotes dopamine neuron formation from precursor cells
- CXCL8 and its mouse version CXCL1 increase neuron production and division
- Chemokine-treated neurons function properly, responding to brain signals
- These findings may help create better cell therapies for dopamine-related disorders
- Alpha-chemokines could support regeneration of dopamine neurons
CREB has a context-dependent role in activity-regulated transcription and maintains neuronal cholesterol homeostasis.
Lemberger T, Parkitna JR, Chai M, Schütz G, Engblom D
CREB and CREM are involved in regulating gene activity in response to brain stimulation, but their role depends on the brain region and type of stimulus. In mice without CREB, cholesterol balance in neurons breaks down, leading to abnormal cholesterol buildup in the brain. This suggests CREB helps maintain brain health beyond just gene regulation.
- CREB is needed for some activity-induced genes in the hippocampus
- CREB loss disrupts cholesterol metabolism in neurons
- CREM can compensate for missing CREB in some cases
- Cholesterol accumulates in brain cells when CREB is absent
- CREB's role varies by brain area and stimulus type
Embryonic stem cell-derived Pitx3-enhanced green fluorescent protein midbrain dopamine neurons survive enrichment by fluorescence-activated cell sorting and function in an animal model of Parkinson's disease.
Hedlund E, Pruszak J, Lardaro T, Ludwig W, Viñuela A, Kim KS, Isacson O
This study developed a method to isolate pure midbrain dopamine neurons from stem cells using a fluorescent marker linked to the Pitx3 gene, which successfully improved survival and function of these neurons when transplanted into a Parkinson's disease model. The purified neurons integrated into the brain, restored movement-related behaviors, and maintained their dopamine-producing identity.
- Stem cell-derived dopamine neurons were purified using a fluorescent tag
- Highly pure dopamine neurons survived and functioned after transplantation
- Transplanted neurons restored movement in Parkinson's disease model rats
- Method could lead to safer, more effective stem cell therapies
- Findings support potential for human cell-based treatments
Unrestricted somatic stem cells from human umbilical cord blood can be differentiated into neurons with a dopaminergic phenotype.
Greschat S, Schira J, Küry P, Rosenbaum C, de Souza Silva MA, Kögler G, Wernet P, Müller HW
Unrestricted somatic stem cells from umbilical cord blood can be turned into dopamine-producing neurons that function like real brain cells, which may offer a potential therapy for conditions like NR4A2-related syndrome.
- Umbilical cord stem cells become dopamine-making neurons
- Cells produce and release dopamine, a key brain chemical
- They show electrical activity like real neurons
- Nurr1, a gene linked to dopamine neurons, is activated
- These cells could be used for future treatments
Epigenetic targets for melatonin: induction of histone H3 hyperacetylation and gene expression in C17.2 neural stem cells.
Sharma R, Ottenhof T, Rzeczkowska PA, Niles LP
Melatonin promotes neural stem cell changes that resemble early brain cell development, including growth of neuron-like structures and increased expression of genes important for dopamine neuron health, such as NURR1. It also enhances histone H3 acetylation, a key epigenetic process that turns on genes involved in cell differentiation.
- Melatonin boosts NURR1 gene expression in neural stem cells
- It increases neuron-like growth and key neural markers
- Melatonin raises histone H3 acetylation, activating gene expression
- Effects are likely mediated by the MT1 melatonin receptor
- These changes support neural differentiation via epigenetic mechanisms
The beta-chemokines CCL2 and CCL7 are two novel differentiation factors for midbrain dopaminergic precursors and neurons.
Edman LC, Mira H, Arenas E
CCL2 and CCL7, two beta-chemokines, help midbrain dopamine neurons develop by pushing precursor cells to become mature dopamine neurons, a process linked to the NR4A2/Nurr1 gene. These chemokines do not affect cell survival or growth but boost neuron extension and maturation, suggesting potential for improving stem cell therapies for Parkinson’s disease.
- CCL2 and CCL7 promote dopamine neuron maturation
- They act specifically on Nurr1+ precursor cells
- They enhance neurite growth in dopamine neurons
- Nurr1 regulates CCL7 expression in development
- Potential use in stem cell therapies for Parkinson’s
Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells.
Smith AG, Luk N, Newton RA, Roberts DW, Sturm RA, Muscat GE
MC1R signaling in melanocytes triggers the rapid production of NR4A nuclear receptors, which help repair DNA damage from UV exposure. People with red hair color variants in MC1R have weaker NR4A responses, making them more vulnerable to UV damage.
- MC1R activation boosts NR4A gene expression in skin cells
- NR4A proteins help fix UV-induced DNA damage
- Red-haired MC1R variants impair this protective response
- NR4A2 is part of a key UV defense pathway in melanocytes
Transcriptional regulation of mesencephalic dopaminergic neurons: the full circle of life and death.
Alavian KN, Scholz C, Simon HH
NR4A2 (NURR1) is a key transcription factor that controls the development, function, and long-term survival of dopamine-producing neurons in the midbrain, which are critical for movement and are lost in Parkinson's disease. This review highlights how NR4A2 and other similar factors regulate these neurons throughout life, offering insights into potential treatments for NR4A2-related disorders.
- NR4A2 is essential for dopamine neuron development and survival
- NR4A2 helps maintain neuron function in adulthood
- Dysfunction in NR4A2 may contribute to neurodegeneration
- Understanding NR4A2 aids in developing therapies for related disorders
Corepressor interaction differentiates the permissive and non-permissive retinoid X receptor heterodimers.
Lammi J, Perlmann T, Aarnisalo P
The way Nurr1 and RXR interact with corepressor proteins explains why Nurr1-RXR pairs respond to RXR ligands, while other similar pairs do not. This difference in corepressor behavior determines whether a receptor complex can be activated by certain drugs.
- Nurr1-RXR complexes release corepressors when RXR ligands bind
- Corepressors stay bound in RAR-RXR complexes unless RAR ligands are present
- The Nurr1 protein's structure controls whether corepressors are released
- This mechanism explains why some drug treatments work for Nurr1 but not other receptors
- Understanding this could help design better treatments for NR4A2-related disorders
Gene Ontology-driven transcriptional analysis of CD34+ cell-initiated megakaryocytic cultures identifies new transcriptional regulators of megakaryopoiesis.
Fuhrken PG, Chen C, Apostolidis PA, Wang M, Miller WM, Papoutsakis ET
This study found that NR4A2, a gene linked to neurological disorders, is active during the development of blood platelets from stem cells, suggesting it may play a role in blood cell formation. The results identify several new genes involved in this process, including NR4A2, which may have broader functions beyond the brain.
- NR4A2 is expressed during platelet development from stem cells
- NR4A2 was among 199 newly identified transcription factors in megakaryocytes
- Protein levels and nuclear localization confirm NR4A2 activity in blood cell formation
- Findings suggest NR4A2 may have roles beyond the nervous system
- This expands understanding of how blood cells develop from stem cells
Orphan nuclear receptor NOR-1 enhances 3',5'-cyclic adenosine 5'-monophosphate-dependent uncoupling protein-1 gene transcription.
Kumar N, Liu D, Wang H, Robidoux J, Collins S
The NR4A family of nuclear receptors, especially NOR-1, plays a key role in turning on the UCP1 gene that controls brown fat heat production in response to cold or stress signals. This process is triggered by cAMP and involves NOR-1 binding directly to a specific site in the UCP1 gene promoter to boost its activity.
- NR4A receptors, especially NOR-1, activate UCP1 gene expression
- Cold or stress signals rapidly increase NOR-1 levels before UCP1
- NOR-1 binds directly to the UCP1 gene promoter
- Blocking NR4A activity stops UCP1 activation
- This pathway is critical for brown fat thermogenesis
Proneural bHLH neurogenin 2 differentially regulates Nurr1-induced dopamine neuron differentiation in rat and mouse neural precursor cells in vitro.
Park CH, Kang JS, Yoon EH, Shim JW, Suh-Kim H, Lee SH
Nurr1 and the protein Ngn2 work differently in rat and mouse brain cells to create dopamine neurons, with Ngn2 boosting Nurr1's effect in mice but blocking it in rats, suggesting species-specific development pathways.
- Ngn2 enhances Nurr1's ability to make dopamine neurons in mouse cells
- Ngn2 suppresses Nurr1 in rat cells, reducing dopamine neuron production
- These differences suggest distinct dopamine neuron development between mice and rats
- Findings may affect how we interpret animal studies for NR4A2-related disorders