Activating transcription factor 5 is required for mouse olfactory bulb development via interneuron

Umemura, Masayuki; Tsunematsu, Kanako; Shimizu, Yusuke; Nakano, Hitoo; Takahashi, Shigeru; Higashiura, Yasutomo; Okabe, Masaru; Takahashi, Yûji

doi:10.1080/09168451.2015.1012042

Cited by 11 publications

(26 citation statements)

References 40 publications

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“…Interestingly, the TFs ATF5 and CREB3L2 are described as transcriptional activators of differentiation processes of adipocytes (Zhao et al, 2014) and chondrocytes (Imamura et al, 2014;Saito et al, 2014), activating transcription by binding to the cAMP response element (Umemura et al, 2015). The TF ASB2 was identified as a growth inhibitor in myeloid leukemia cells (Guibal et al, 2002) through promoting ubiquitination of Notch targets such as E2A and JAK2 (Nie et al, 2011).…”

Section: Novel and Potentially Important Tfs For Th2 Cell Fate Decisionsmentioning

confidence: 99%

Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions

et al. 2016

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ABSTRACT. Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hif1a) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes.

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Section: Novel and Potentially Important Tfs For Th2 Cell Fate Decisionsmentioning

confidence: 99%

Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions

et al. 2016

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“…All mouse studies were approved by the Institutional Animal Experiment Committee of the university, and were performed in accordance with institutional and governmental guidelines. ATF5-deficient (ATF5 −/− ) mice were generated by targeting exon 3, which was replaced with a neomycin-resistant gene, and then deleted by Cre recombinase (Umemura et al 2015). Mice were genotyped as previously described (Umemura et al 2015).…”

Section: Micementioning

confidence: 99%

“…Actually, the size of the olfactory bulb is reduced in ATF5 −/− mice compared with that in the wild-type (Umemura et al 2015), and olfactory sensory neurons (OSNs) in the ATF5 −/− MOE remain immature and frequently undergo apoptosis (Wang et al 2012;Umemura et al 2015). In addition, ATF5 −/− mice display reduced inter-male aggression (Umemura et al 2015), and this behavior is regulated by the vomeronasal sensory system (Stowers et al 2002;Chamero et al 2011;Prince et al 2013), but also by the main olfactory sensory system (Mandiyan et al 2005;Wang et al 2006;Matsuo et al 2015). In this study, we investigated the effect of deficiency of ATF5 in VSNs using ATF5 −/− mice.…”

Section: Introductionmentioning

confidence: 99%

“…We and other research groups have recently reported that twothirds of ATF5-deficient (ATF5 −/− ) mice die just after birth partly due to a failure to suckle milk (Wang et al 2012;Umemura et al 2015), a phenotype frequently observed in mice with the knockout of genes related to olfactory function (Belluscio et al 1998;Wong et al 2000). Actually, the size of the olfactory bulb is reduced in ATF5 −/− mice compared with that in the wild-type (Umemura et al 2015), and olfactory sensory neurons (OSNs) in the ATF5 −/− MOE remain immature and frequently undergo apoptosis (Wang et al 2012;Umemura et al 2015). In addition, ATF5 −/− mice display reduced inter-male aggression (Umemura et al 2015), and this behavior is regulated by the vomeronasal sensory system (Stowers et al 2002;Chamero et al 2011;Prince et al 2013), but also by the main olfactory sensory system (Mandiyan et al 2005;Wang et al 2006;Matsuo et al 2015).…”

Section: Introductionmentioning

confidence: 99%

“…The ATF5 mRNA has two upstream open reading frames (uORFs) in its 5′ untranslated region (5′-UTR), which confers its protein translation via eIF2α-phosphorylation by oxidative and ER stresses (Watatani et al 2008;Zhou et al 2008;Hatano et al 2013). We and other research groups have recently reported that twothirds of ATF5-deficient (ATF5 −/− ) mice die just after birth partly due to a failure to suckle milk (Wang et al 2012;Umemura et al 2015), a phenotype frequently observed in mice with the knockout of genes related to olfactory function (Belluscio et al 1998;Wong et al 2000). Actually, the size of the olfactory bulb is reduced in ATF5 −/− mice compared with that in the wild-type (Umemura et al 2015), and olfactory sensory neurons (OSNs) in the ATF5 −/− MOE remain immature and frequently undergo apoptosis (Wang et al 2012;Umemura et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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Activating transcription factor 5 (ATF5) is essential for the maturation and survival of mouse basal vomeronasal sensory neurons

et al. 2015

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Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of transcription factors, which is highly expressed in olfactory chemosensory tissues, the main olfactory epithelium and vomeronasal epithelium (VNE) in mice. The vomeronasal sensory neurons in the VNE detect pheromones in order to regulate social behaviors such as mating and aggression; however, the physiological role of ATF5 in the vomeronasal sensory system remains unknown. In this study, we found that the differentiation of mature vomeronasal sensory neurons, assessed by olfactory marker protein expression, was inhibited in ATF5-deficient VNE. In addition, many apoptotic vomeronasal sensory neurons were evident in ATF5-deficient VNE. The vomeronasal sensory neurons consist of two major types of neuron expressing either vomeronasal 1 receptor (V1r)/Gαi2 or vomeronasal 2 receptor (V2r)/Gαo. We demonstrated that the differentiation, survival and axonal projection of V2r/Gαo-type rather than V1r/Gαi2-type vomeronasal sensory neurons were severely inhibited in ATF5-deficient VNE. These results suggest that ATF5 is one of the transcription factors crucial for the vomeronasal sensory formation.

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Gene duplication, conservation, and divergence of activating transcription factor 5 gene in zebrafish

Zhu

Zhang

et al. 2022

J Exp Zool Pt B

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Activating transcription factor 5 (Atf5) is a member of the ATF/CREB family of transcription factors and involved in diverse cellular functions and diseases in mammals. However, the function of atf5 remains largely unknown in fish. Here, we report the expression pattern and function of duplicated atf5 genes in zebrafish. The results showed that the gene structures of zebrafish atf5a and atf5b were similar to their mammalian orthologs. Zebrafish Atf5a and Atf5b shared an amino acid sequence identity of 40.7%. Zebrafish atf5a and atf5b had maternal origin with dynamic expression during embryonic development. Zebrafish atf5a mRNA is mainly enriched in olfactory epithelium, midbrain, and hindbrain, while zebrafish atf5b mRNA is mainly detected in midbrain, hindbrain, and liver during embryogenesis. The results of acute hypoxia experiment showed that atf5a mRNA was significantly upregulated in the brain, liver, and muscle, while atf5b mRNA was just increased significantly in the brain. Functional analysis showed that knockdown of atf5a affects the development of the ciliated neurons in zebrafish embryos. The effect was enhanced when atf5a MO was co-injected with atf5b MO. The development of ciliated neurons in zebrafish embryos was not affected by injection of atf5b MO alone. atf5a knockdown also affects the development of early-born olfactory neurons. The effects caused by atf5a knockdown could be rescued by atf5b mRNA.These results suggest that the duplicated atf5 genes may have evolved divergently and play redundant biological roles in the development of olfactory sensory neurons in zebrafish.

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Activating transcription factor 5 is required for mouse olfactory bulb development via interneuron

Cited by 11 publications

References 40 publications

Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions

Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions

Activating transcription factor 5 (ATF5) is essential for the maturation and survival of mouse basal vomeronasal sensory neurons

Gene duplication, conservation, and divergence of activating transcription factor 5 gene in zebrafish

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