The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function

Pandolfi, Erica C.; Breuer, Joseph; Huu, Viet Anh Nguyen; Talluri, Tulasi; Nguyen, Duong; Lee, Jessica Sora; Hu, Rachael J.; Bharti, Kapil; Skowronska‐Krawczyk, Dorota; Gorman, Michael R.; Mellon, Pamela L.; Hoffmann, Hanne M.

doi:10.1007/s12035-019-01781-9

Cited by 13 publications

(17 citation statements)

References 85 publications

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“…Six3 and Vax1 are important for eye and brain development, whereas their roles in the post‐developmental brain are far less studied. We confirmed that expression of both Six3 and Vax1 is maintained in the adult hypothalamus, and both genes are highly expressed in the SCN (Pandolfi, Breuer, et al, 2019; VanDunk et al., 2011). We recently showed that conditional deletion of Vax1 in the developing SCN impacts circadian rhythms of wheel‐running activity (Pandolfi, Breuer, et al, 2019).…”

Section: Discussionsupporting

confidence: 75%

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The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice

Hoffmann

Meadows

Breuer

et al. 2021

J of Neuroscience Research

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The homeodomain transcription factors sine oculis homeobox 3 (Six3) and ventral anterior homeobox 1 (Vax1) are required for brain development. Their expression in specific brain areas is maintained in adulthood, where their functions are poorly understood. To identify the roles of Six3 and Vax1 in neurons, we conditionally deleted each gene using Synapsin cre , a promoter targeting maturing neurons, and generated

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Section: Discussionsupporting

confidence: 75%

“…in the developing SCN impacts circadian rhythms of wheelrunning activity(Pandolfi, Breuer, et al, 2019). To shed light on TA B L E 5 Circadian parameters in Vax1 syn Analysis of circadian parameters of Vax1 fl/fl and Vax1 syn females on running wheels.…”

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confidence: 99%

The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice

Hoffmann

Meadows

Breuer

et al. 2021

J of Neuroscience Research

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“…Using conditional KO mice (Cre-LoxP system) comes with numerous potential caveats to consider in data interpretation [ 43 , [73] , [74] , [75] , [76] , [77] , [78] ]. We have recently further validated the effectiveness of the Synapsin cre -allele for inducing recombination of the Six3 flox -allele throughout the brain, including the SCN, PVN, and PeVN [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Deletion of Six3 in post-proliferative neurons produces weakened SCN circadian output, improved metabolic function, and dwarfism in male mice

Meadows

Breuer

Lavalle

et al. 2022

Molecular Metabolism

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Objective The increasing prevalence of obesity makes it important to increase the understanding of the maturation and function of the neuronal integrators and regulators of metabolic function. Methods Behavioral, molecular, and physiological analyses of transgenic mice with Sine oculis 3 ( Six3 ) deleted in mature neurons using the Synapsin cre allele. Results Conditional deletion of the homeodomain transcription factor Six3 in mature neurons causes dwarfism and weakens circadian wheel-running activity rhythms but increases general activity at night, and improves metabolic function, without impacting pubertal onset or fertility in males. The reduced growth in 6-week-old Six3 fl/fl :Synapsin cre ( Six3 syn ) males correlates with increased somatostatin (SS) expression in the hypothalamus and reduced growth hormone (GH) in the pituitary. In contrast, 12-week-old Six3 syn males have increased GH release, despite an increased number of the inhibitory SS neurons in the periventricular nucleus. GH is important in glucose metabolism, muscle function, and bone health. Interestingly, Six3 syn males have improved glucose tolerance at 7, 12, and 18 weeks of age, which, in adulthood, is associated with increased % lean mass and increased metabolic rates. Further, 12-week-old Six3 syn males have reduced bone mineralization and a lower bone mineral density, indicating that reduced GH levels during early life cause a long-term reduction in bone mineralization. Conclusion Our study points to the novel role of Six3 in post-proliferative neurons to regulate metabolic function through SS neuron control of GH release.

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“…Six6 is required for early eye development, GnRH neuron, and SCN development in vertebrates [ 32 , 33 ]. The suprachiasmatic nucleus (SCN), the brain’s primary circadian pacemaker, is required to translate day-length and circadian rhythms into neuronal, hormonal, and behavioral rhythms [ 34 ]. Migration is a rhythmic behavior.…”

Section: Discussionmentioning

confidence: 99%

Whole-genome resequencing of three Coilia nasus population reveals genetic variations in genes related to immune, vision, migration, and osmoregulation

Gao

2021

BMC Genomics

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Background Coilia nasus is an important anadromous fish, widely distributed in China, Japan, and Korea. Based on morphological and ecological researches of C. nasus, two ecotypes were identified. One is the anadromous population (AP). The sexually mature fish run thousands of kilometers from marine to river for spawning. Another one is the resident population which cannot migrate. Based on their different habitats, they were classified into landlocked population (LP) and sea population (SP) which were resident in the freshwater lake and marine during the entire lifetime, respectively. However, they have never been systematically studied. Moreover, C. nasus is declining sharply due to overfishing and pollution recently. Therefore, further understandings of C. nasus populations are needed for germplasm protection. Results Whole-genome resequencing of AP, LP, and SP were performed to enrich the understanding of different populations of C. nasus. At the genome level, 3,176,204, 3,307,069, and 3,207,906 single nucleotide polymorphisms (SNPs) and 1,892,068, 2,002,912, and 1,922,168 insertion/deletion polymorphisms (InDels) were generated in AP, LP, and SP, respectively. Selective sweeping analysis showed that 1022 genes were selected in AP vs LP; 983 genes were selected in LP vs SP; 116 genes were selected in AP vs SP. Among them, selected genes related to immune, vision, migration, and osmoregulation were identified. Furthermore, their expression profiles were detected by quantitative real-time PCR. Expression levels of selected genes related to immune, and vision in LP were significantly lower than AP and SP. Selected genes related to migration in AP were expressed significantly more highly than LP. Expression levels of selected genes related to osmoregulation were also detected. The expression of NKAα and NKCC1 in LP were significantly lower than SP, while expression of NCC, SLC4A4, NHE3, and V-ATPase in LP was significantly higher than SP. Conclusions Combined to life history of C. nasus populations, our results revealed that the molecular mechanisms of their differences of immune, vision, migration, and osmoregulation. Our findings will provide a further understanding of different populations of C. nasus and will be beneficial for wild C. nasus protection.

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The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function

Cited by 13 publications

References 85 publications

The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice

The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice

Deletion of Six3 in post-proliferative neurons produces weakened SCN circadian output, improved metabolic function, and dwarfism in male mice

Whole-genome resequencing of three Coilia nasus population reveals genetic variations in genes related to immune, vision, migration, and osmoregulation

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