AP-1<sup>c-Jun/FosB</sup>mediates xFoxD5b expression in Xenopus early developmental neurogenesis

Yoon, Jaeho; Kim, Jung Ho; Lee, Ok Joo; Lee, Sung Young; Lee, Seung Hwan; Park, Jae Bong; Lee, Jae Yong; Kim, Sung Chan; Kim, Jaebong

doi:10.1387/ijdb.130163jk

Cited by 8 publications

(8 citation statements)

References 37 publications

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“…However, no clear evidence was obtained that either c-fos −/− or c-fos +/+ embryos contained Fra-2-containing AP-1 dimers. It is still unknown whether different combinations of AP-1 components regulate specific neural genes differently or whether a single combination of AP-1 plays a more general role in various neural genes [ 50 ], thus rendering an even more complicated scenario for genetically tracking the multiplicity of AP-1 dimers and the outcome of their activity in mammalian cells. By no doubt, a more detailed study of the regulatory capacity of c-Fos-containing or c-Fos non-containing AP-1 transcriptional factors will help to understand the physiological differences observed in these mice.…”

Section: Discussionmentioning

confidence: 99%

Brain development is impaired inc-fos−/− mice

et al. 2015

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c-Fos is a proto-oncogene involved in diverse cellular functions. Its deregulation has been associated to abnormal development and oncogenic progression. c-fos−/− mice are viable but present a reduction in their body weight and brain size. We examined the importance of c-Fos during neocortex development at 13.5, 14.5 and 16.5 days of gestation. At E14.5, neocortex thickness, apoptosis, mitosis and expression of markers along the different stages of Neural Stem Progenitor Cells (NSPCs) differentiation in c-fos−/− and wild-type mice were analyzed. A ∼15% reduction in the neocortex thickness of c-fos−/− embryos was observed which correlates with a decrease in the number of differentiated cells and an increase in apoptosis at the ventricular zone. No difference in mitosis rate was observed, although the mitotic angle was predominantly vertical in c-fos−/− embryos, suggesting a reduced trend of NSPCs to differentiate. At E13.5, changes in differentiation markers start to be apparent and are still clearly observed at E16.5. A tendency of more AP-1/DNA complexes present in nuclear extracts of cerebral cortex from c-fos−/− embryos with no differences in the lipid synthesis activity was found. These results suggest that c-Fos is involved in the normal development of NSPCs by means of its AP-1 activity.

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Section: Discussionmentioning

confidence: 99%

Brain development is impaired inc-fos−/− mice

et al. 2015

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“…For negative regulation, BMP/Ventx1.1 strongly inhibits foxd4l1.1 expression and neural differentiation in the ectodermal region. The foxd4l1.1 promoter contains Ventx1.1 response elements (VREs) within its proximal region where Ventx1.1 binds and inhibits transcription [14,15]. These reciprocal inhibitory pathways involving Foxd4l1.1 contribute to the fine-tuning of neural and non-neural fate specification.…”

Section: Introductionmentioning

confidence: 99%

Foxd4l1.1 Negatively Regulates Chordin Transcription in Neuroectoderm of Xenopus Gastrula

Kim

Goutam

Umair

et al. 2021

Cells

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Inhibition of the bone morphogenetic proteins (BMPs) is the primary step toward neuroectoderm formation in vertebrates. In this process, the Spemann organizer of the dorsal mesoderm plays a decisive role by secreting several extracellular BMP inhibitors such as Chordin (Chrd). Chrd physically interacts with BMP proteins and inhibits BMP signaling, which triggers the expression of neural-specific transcription factors (TFs), including Foxd4l1.1. Thus, Chrd induces in a BMP-inhibited manner and promotes neuroectoderm formation. However, the regulatory feedback mechanism of Foxd4l1.1 on mesodermal genes expression during germ-layer specification has not been fully elucidated. In this study, we investigated the regulatory mechanism of Foxd4l1.1 on chrd (a mesodermal gene). We demonstrate that Foxd4l1.1 inhibits chrd expression during neuroectoderm formation in two ways: First, Foxd4l1.1 directly binds to FRE (Foxd4l1.1 response elements) within the chrd promoter region to inhibit transcription. Second, Foxd4l1.1 physically interacts with Smad2 and Smad3, and this interaction blocks Smad2 and Smad3 binding to activin response elements (AREs) within the chrd promoter. Site-directed mutagenesis of FRE within the chrd(-2250) promoter completely abolished repressor activity of the Foxd4l1.1. RT-PCR and reporter gene assay results indicate that Foxd4l1.1 strongly inhibits mesoderm- and ectoderm-specific marker genes to maintain neural fate. Altogether, these results suggest that Foxd4l1.1 negatively regulates chrd transcription by dual mechanism. Thus, our study demonstrates the existence of precise reciprocal regulation of chrd transcription during neuroectoderm and mesoderm germ-layer specification in Xenopus embryos.

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“…Further, transition of ectoderm-neuroectoderm is regulated by fine-tuning of several transcription factors such as foxd4l1.1 , zic2/3 , sox1-3/d and xiro1-3 25 , 35 . Foxd4l1.1 has been documented to increase the expression of neural specific genes, including sox2/3 , geminin , n-tubulin , ncam , and neuroD in a dose-dependent manner, leading to neural differentiation 36 . Also, ectopic expression of foxd4l1.1 inhibits BMP4/Smad1 signaling and leads to neural differentiation and neuroectoderm formation 34 .…”

Section: Introductionmentioning

confidence: 99%

Foxd4l1.1 negatively regulates transcription of neural repressor ventx1.1 during neuroectoderm formation in Xenopus embryos

Kumar

Umair

Kim

et al. 2020

Sci Rep

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Neuroectoderm formation is the first step in development of a proper nervous system for vertebrates. The developmental decision to form a non-neural ectoderm versus a neural one involves the regulation of BMP signaling, first reported many decades ago. However, the precise regulatory mechanism by which this is accomplished has not been fully elucidated, particularly for transcriptional regulation of certain key transcription factors. BMP4 inhibition is a required step in eliciting neuroectoderm from ectoderm and Foxd4l1.1 is one of the earliest neural genes highly expressed in the neuroectoderm and conserved across vertebrates, including humans. In this work, we focused on how Foxd4l1.1 downregulates the neural repressive pathway. Foxd4l1.1 inhibited BMP4/Smad1 signaling and triggered neuroectoderm formation in animal cap explants of Xenopus embryos. Foxd4l1.1 directly bound within the promoter of endogenous neural repressor ventx1.1 and inhibited ventx1.1 transcription. Foxd4l1.1 also physically interacted with Xbra in the nucleus and inhibited Xbra-induced ventx1.1 transcription. In addition, Foxd4l1.1 also reduced nuclear localization of Smad1 to inhibit Smad1-mediated ventx1.1 transcription. Foxd4l1.1 reduced the direct binding of Xbra and Smad1 on ventx1.1 promoter regions to block Xbra/Smad1-induced synergistic activation of ventx1.1 transcription. Collectively, Foxd4l1.1 negatively regulates transcription of a neural repressor ventx1.1 by multiple mechanisms in its exclusively occupied territory of neuroectoderm, and thus leading to primary neurogenesis. In conjunction with the results of our previous findings that ventx1.1 directly represses foxd4l1.1, the reciprocal repression of ventx1.1 and foxd4l1.1 is significant in at least in part specifying the mechanism for the non-neural versus neural ectoderm fate determination in Xenopus embryos.

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AP-1^c-Jun/FosBmediates xFoxD5b expression in Xenopus early developmental neurogenesis

Cited by 8 publications

References 37 publications

Brain development is impaired inc-fos−/− mice

Brain development is impaired inc-fos−/− mice

Foxd4l1.1 Negatively Regulates Chordin Transcription in Neuroectoderm of Xenopus Gastrula

Foxd4l1.1 negatively regulates transcription of neural repressor ventx1.1 during neuroectoderm formation in Xenopus embryos

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AP-1c-Jun/FosBmediates xFoxD5b expression in Xenopus early developmental neurogenesis

Cited by 8 publications

References 37 publications

Brain development is impaired inc-fos−/− mice

Brain development is impaired inc-fos−/− mice

Foxd4l1.1 Negatively Regulates Chordin Transcription in Neuroectoderm of Xenopus Gastrula

Foxd4l1.1 negatively regulates transcription of neural repressor ventx1.1 during neuroectoderm formation in Xenopus embryos

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AP-1^c-Jun/FosBmediates xFoxD5b expression in Xenopus early developmental neurogenesis