The proto‐oncogene <i>BCL6</i> promotes survival of olfactory sensory neurons

Otaki, Joji M.; Hatano, Masahiko; Matayoshi, Rie; Tokuhisa, Takeshi; Yamamoto, Hirokazu

doi:10.1002/dneu.20786

Cited by 9 publications

(5 citation statements)

References 53 publications

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“…Heterogeneous infection in various parts of the pupae was observed, even at identical virus titers. The variability is unavoidable as it has been observed with baculovirus [ 31 , 32 ], Sindbis virus [ 34 ], and other viral systems [ 35 – 37 ]. Thus, we believe that the common tendency is more important than the variation in the five induced cases.…”

Section: Discussionmentioning

confidence: 99%

Distal-less induces elemental color patterns in Junonia butterfly wings

et al. 2016

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BackgroundThe border ocellus, or eyespot, is a conspicuous color pattern element in butterfly wings. For two decades, it has been hypothesized that transcription factors such as Distal-less (Dll) are responsible for eyespot pattern development in butterfly wings, based on their expression in the prospective eyespots. In particular, it has been suggested that Dll is a determinant for eyespot size. However, functional evidence for this hypothesis has remained incomplete, due to technical difficulties.ResultsHere, we show that ectopically expressed Dll induces ectopic elemental color patterns in the adult wings of the blue pansy butterfly, Junonia orithya (Lepidoptera, Nymphalidae). Using baculovirus-mediated gene transfer, we misexpressed Dll protein fused with green fluorescent protein (GFP) in pupal wings, resulting in ectopic color patterns, but not the formation of intact eyespots. Induced changes included clusters of black and orange scales (a basic feature of eyespot patterns), black and gray scales, and inhibition of cover scale development. In contrast, ectopic expression of GFP alone did not induce any color pattern changes using the same baculovirus-mediated gene transfer system.ConclusionsThese results suggest that Dll plays an instructive role in the development of color pattern elements in butterfly wings, although Dll alone may not be sufficient to induce a complete eyespot. This study thus experimentally supports the hypothesis of Dll function in eyespot development.

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Section: Discussionmentioning

confidence: 99%

Distal-less induces elemental color patterns in Junonia butterfly wings

et al. 2016

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“…MEF2D , STAT3 , and B-cell CLL/lymphoma 6 ( BCL6 ) have all been shown to promote survival of neurons [37], [38], [39]. MEF2D and STAT3 show the highest expression during IBA, while BCL6 is elevated in October, torpor, and IBA (Figure 6A).…”

Section: Discussionmentioning

confidence: 99%

Seasonal and Regional Differences in Gene Expression in the Brain of a Hibernating Mammal

2013

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Mammalian hibernation presents a unique opportunity to study naturally occurring neuroprotection. Hibernating ground squirrels undergo rapid and extreme physiological changes in body temperature, oxygen consumption, and heart rate without suffering neurological damage from ischemia and reperfusion injury. Different brain regions show markedly different activity during the torpor/arousal cycle: the cerebral cortex shows activity only during the periodic returns to normothermia, while the hypothalamus is active over the entire temperature range. Therefore, region-specific neuroprotective strategies must exist to permit this compartmentalized spectrum of activity. In this study, we use the Illumina HiSeq platform to compare the transcriptomes of these two brain regions at four collection points across the hibernation season: April Active, October Active, Torpor, and IBA. In the cerebral cortex, 1,085 genes were found to be differentially expressed across collection points, while 1,063 genes were differentially expressed in the hypothalamus. Comparison of these transcripts indicates that the cerebral cortex and hypothalamus implement very different strategies during hibernation, showing less than 20% of these differentially expressed genes in common. The cerebral cortex transcriptome shows evidence of remodeling and plasticity during hibernation, including transcripts for the presynaptic cytomatrix proteins bassoon and piccolo, and extracellular matrix components, including laminins and collagens. Conversely, the hypothalamic transcriptome displays upregulation of transcripts involved in damage response signaling and protein turnover during hibernation, including the DNA damage repair gene RAD50 and ubiquitin E3 ligases UBR1 and UBR5. Additionally, the hypothalamus transcriptome also provides evidence of potential mechanisms underlying the hibernation phenotype, including feeding and satiety signaling, seasonal timing mechanisms, and fuel utilization. This study provides insight into potential neuroprotective strategies and hibernation control mechanisms, and also specifically shows that the hibernator brain exhibits both seasonal and regional differences in mRNA expression.

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“…Bcl6 has also been shown to repress the programmed cell death 2 gene (PDCD2) in lymphoma cell lines, and its expression is inverse to that of PDCD2 in lymphocytes and follicular mantle cells in vivo (70), suggestive of a critical role during immune system development and function. Bcl6 knockout mice display elevated levels of apoptosis during spermatogenesis (71), and Bcl6 is required for the survival of differentiating olfactory neurons (24). Indeed, in many cell types that express Bcl6, terminal differentiation requires that apoptosis be inhibited, and it is thought that Bcl6 may mediate this inhibition (72 -76).…”

Section: Discussionmentioning

confidence: 99%

“…While the involvement of BCL6 in B cell development and lymphomagenesis has been well studied in knockout mice (21,22) and cell culture (23), its functions during embryonic development remain poorly elucidated. Outside of the immune system, BCL6 is known to function in the development of the olfactory system, where it also serves as an anti-apoptotic factor during olfactory sensory neuron differentiation (24). Recently, BCL6 has been reported to be involved in the development of left-right asymmetry during Xenopus embryogenesis by inhibiting Notch target genes and thereby maintaining the expression of Pitx2 in the left lateral plate mesoderm (25).…”

Section: Introductionmentioning

confidence: 99%

Bcl6a function is required during optic cup formation to prevent p53-dependent apoptosis and colobomata

Lee

Gross

2013

Human Molecular Genetics

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Mutations in BCOR (Bcl6 corepressor) are found in patients with oculo-facio-cardio-dental (OFCD) syndrome, a congenital disorder affecting visual system development, and loss-of-function studies in zebrafish and Xenopus demonstrate a role for Bcor during normal optic cup development in preventing colobomata. The mechanism whereby BCOR functions during eye development to prevent colobomata is not known, but in other contexts it serves as a transcriptional corepressor that potentiates transcriptional repression by B cell leukemia/lymphoma 6 (BCL6). Here, we have explored the function of the zebrafish ortholog of Bcl6, Bcl6a, during eye development, and our results demonstrate that Bcl6a, like Bcor, is required to prevent colobomata during optic cup formation. Our data demonstrate that Bcl6a acts downstream of Vax1 and Vax2, known regulators of ventral optic cup formation and choroid fissure closure, and that bcl6a is a direct target of Vax2. Together, this regulatory network functions to repress p53 expression and thereby suppress apoptosis in the developing optic cup. Furthermore, our data demonstrate that Bcl6a functions cooperatively with Bcor, Rnf2 and Hdac1 in a common gene regulatory network that acts to repress p53 and prevent colobomata. Together, these data support a model in which p53-dependent apoptosis needs to be tightly regulated for normal optic cup formation and that Bcl6a, Bcor, Rnf2 and Hdac1 activities mediate this regulation.

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The proto‐oncogene BCL6 promotes survival of olfactory sensory neurons

Cited by 9 publications

References 53 publications

Distal-less induces elemental color patterns in Junonia butterfly wings

Distal-less induces elemental color patterns in Junonia butterfly wings

Seasonal and Regional Differences in Gene Expression in the Brain of a Hibernating Mammal

Bcl6a function is required during optic cup formation to prevent p53-dependent apoptosis and colobomata

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