xCOUP-TF-B regulates xCyp26 transcription and modulates retinoic acid signaling for anterior neural patterning in Xenopus

Tanibe, Misaki; Ishiura, Shoichi; Asashima, Makoto; Michiue, Tatsuo

doi:10.1387/ijdb.113482mt

Cited by 5 publications

(4 citation statements)

References 26 publications

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“…Similarly, the C. elegans ortholog UNC55 acts in cell fate determination, enabling the differentiation of two discrete populations of motor neurons (Walthall and Plunkett, 1995 ; Mimi Zhou and Walthall, 1998 ; Petersen et al, 2011 ). Finally, in X. laevis, xCOUP-TFA and B direct the antero-posterior patterning of the central nervous system (Van Der Wees et al, 1996 ; Tanibe et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Tocco

Bertacchi

Studer

2021

Front. Mol. Neurosci.

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The assembly and maturation of the mammalian brain result from an intricate cascade of highly coordinated developmental events, such as cell proliferation, migration, and differentiation. Any impairment of this delicate multi-factorial process can lead to complex neurodevelopmental diseases, sharing common pathogenic mechanisms and molecular pathways resulting in multiple clinical signs. A recently described monogenic neurodevelopmental syndrome named Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) is caused by NR2F1 haploinsufficiency. The NR2F1 gene, coding for a transcriptional regulator belonging to the steroid/thyroid hormone receptor superfamily, is known to play key roles in several brain developmental processes, from proliferation and differentiation of neural progenitors to migration and identity acquisition of neocortical neurons. In a clinical context, the disruption of these cellular processes could underlie the pathogenesis of several symptoms affecting BBSOAS patients, such as intellectual disability, visual impairment, epilepsy, and autistic traits. In this review, we will introduce NR2F1 protein structure, molecular functioning, and expression profile in the developing mouse brain. Then, we will focus on Nr2f1 several functions during cortical development, from neocortical area and cell-type specification to maturation of network activity, hippocampal development governing learning behaviors, assembly of the visual system, and finally establishment of cortico-spinal descending tracts regulating motor execution. Whenever possible, we will link experimental findings in animal or cellular models to corresponding features of the human pathology. Finally, we will highlight some of the unresolved questions on the diverse functions played by Nr2f1 during brain development, in order to propose future research directions. All in all, we believe that understanding BBSOAS mechanisms will contribute to further unveiling pathophysiological mechanisms shared by several neurodevelopmental disorders and eventually lead to effective treatments.

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Section: Discussionmentioning

confidence: 99%

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Tocco

Bertacchi

Studer

2021

Front. Mol. Neurosci.

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“…Several DE TF-encoding genes ( gbx2 . 2, greb1, hand1, hnf1b, mespa, mespb, nr2f2, ripply3, tbx1, tcf21, znf703 ) have also been previously reported to be RA targets in various contexts (Brophy et al, 2017; Deimling and Drysdale, 2009; Gere-Becker et al, 2018; Janesick et al, 2019, 2012; Moreno et al, 2008; Tanibe et al, 2012; von Bubnoff et al, 1996). Another prominent group of DE TF corresponded to hox genes.…”

Section: Resultsmentioning

confidence: 92%

“…At NFst14, they included TF known to play a central role in pronephros specification, like pax8 and lhx1 (Carroll and Vize, 1999), which have been previously shown to be down-regulated in LMZ explants by RA disruption (Le Bouffant et al, 2012), and osr2, irx3 and mecom whose depletion strongly affects pronephric development (Alarcon et al, 2008; Tena et al, 2007; Van Campenhout et al, 2006). Several DE TF-encoding genes ( gbx2.2, greb1, hand1, hnf1b, mespa, mespb, nr2f2, ripply3, tbx1, tcf21, znf703 ) have also been previously reported to be RA targets in various contexts (Brophy et al, 2017; Deimling and Drysdale, 2009; Gere-Becker et al, 2018; Janesick et al, 2019, 2012; Moreno et al, 2008; Tanibe et al, 2012; von Bubnoff et al, 1996). Another prominent group of DE TF corresponded to hox genes.…”

Section: Resultsmentioning

confidence: 96%

Retinoic acid control of pax8 during renal specification of Xenopus pronephros involves hox and meis3

Jennifer

Suzuki

Ochi

et al. 2022

Preprint

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Development of the Xenopus pronephros relies on renal precursors grouped at neurula stage into a specific region of dorso-lateral mesoderm called the kidney field. Formation of the kidney field at early neurula stage is dependent on retinoic (RA) signaling acting upstream of renal master transcriptional regulators such as pax8 or lhx1. Although lhx1 might be a direct target of RA-mediated transcriptional activation in the kidney field, how RA controls the emergence of the kidney field remains poorly understood. In order to better understand RA control of renal specification of the kidney field, we have performed a transcriptomic profiling of genes affected by RA disruption in lateral mesoderm explants isolated prior to the emergence of the kidney field and cultured at different time points until early neurula stage. Besides genes directly involved in pronephric development (pax8, lhx1, osr2, mecom), hox (hoxa1, a3, b3, b4, c5 and d1) and the hox co-factor meis3 appear as a prominent group of genes encoding transcription factors (TFs) downstream of RA. Supporting the idea of a role of meis3 in the kidney field, we have observed that meis3 depletion results in a severe inhibition of pax8 expression in the kidney field. Meis3 depletion only marginally affects expression of lhx1 and aldh1a2 suggesting that meis3 principally acts upstream of pax8. Further arguing for a role of meis3 and hox in the control of pax8, expression of a combination of meis3, hoxb4 and pbx1 in animal caps induces pax8 expression, but not that of lhx1. The same combination of TFs is also able to transactivate a previously identified pax8 enhancer, Pax8-CNS1. Mutagenesis of potential PBX-Hox binding motifs present in Pax8-CNS1 further allows to identify two of them that are necessary for transactivation. Finally, we have tested deletions of regulatory sequences in reporter assays with a previously characterized transgene encompassing 36.5 kb of the X. tropicalis pax8 gene that allows expression of a truncated pax8-GFP fusion protein recapitulating endogenous pax8 expression. This transgene includes three conserved pax8 enhancers, Pax8-CNS1, Pax8-CNS2 and Pax8-CNS3. Deletion of Pax8-CNS1 alone does not affect reporter expression, but deletion of a 3.5kb region encompassing Pax8-CNS1 and Pax8-CNS2 results in a severe inhibition of reporter expression both in the otic placode and kidney field domains.

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“…It is widely accepted that RA is a negative regulator of anterior brain regions based on extensive experimental evidence describing the transformation of anterior neural tissues to more posterior identities following RA treatment or mutation of genes involved in the attenuation of the RA signal ( Durston et al, 1989 ; Sive et al, 1990 ; Hollemann et al, 1998 ; Koide et al, 2001 ; Ribes et al, 2007 ; Tanibe et al, 2008 ; Nolte et al, 2019 ). During early stages of brain development, the neuroectodermal region rostral to the midbrain-hindbrain boundary expresses CYP26A1 performing a protective role by hydroxylation and subsequent degradation of RA secreted from adjacent tissues ( Koide et al, 2001 ; Weston et al, 2003 ; Tanibe et al, 2012 ; Zhong et al, 2019 ). Our results show that very early in gastrulation, RA signaling is also required for the development of a normal head.…”

Section: Discussionmentioning

confidence: 99%

Reduced Retinoic Acid Signaling During Gastrulation Induces Developmental Microcephaly

Gur

Bendelac-Kapon

Shabtai

et al. 2022

Front. Cell Dev. Biol.

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Retinoic acid (RA) is a central signaling molecule regulating multiple developmental decisions during embryogenesis. Excess RA induces head malformations, primarily by expansion of posterior brain structures at the expense of anterior head regions, i.e., hindbrain expansion. Despite this extensively studied RA teratogenic effect, a number of syndromes exhibiting microcephaly, such as DiGeorge, Vitamin A Deficiency, Fetal Alcohol Syndrome, and others, have been attributed to reduced RA signaling. This causative link suggests a requirement for RA signaling during normal head development in all these syndromes. To characterize this novel RA function, we studied the involvement of RA in the early events leading to head formation in Xenopus embryos. This effect was mapped to the earliest RA biosynthesis in the embryo within the gastrula Spemann-Mangold organizer. Head malformations were observed when reduced RA signaling was induced in the endogenous Spemann-Mangold organizer and in the ectopic organizer of twinned embryos. Two embryonic retinaldehyde dehydrogenases, ALDH1A2 (RALDH2) and ALDH1A3 (RALDH3) are initially expressed in the organizer and subsequently mark the trunk and the migrating leading edge mesendoderm, respectively. Gene-specific knockdowns and CRISPR/Cas9 targeting show that RALDH3 is a key enzyme involved in RA production required for head formation. These observations indicate that in addition to the teratogenic effect of excess RA on head development, RA signaling also has a positive and required regulatory role in the early formation of the head during gastrula stages. These results identify a novel RA activity that concurs with its proposed reduction in syndromes exhibiting microcephaly.

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xCOUP-TF-B regulates xCyp26 transcription and modulates retinoic acid signaling for anterior neural patterning in Xenopus

Abstract: Early embryogenesis in

Cited by 5 publications

References 26 publications

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Retinoic acid control of pax8 during renal specification of Xenopus pronephros involves hox and meis3

Reduced Retinoic Acid Signaling During Gastrulation Induces Developmental Microcephaly

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