New Insights into the Control of Cell Fate Choices and Differentiation by Retinoic Acid in Cranial, Axial and Caudal Structures

Draut, Heidrun; Liebenstein, Thomas; Begemann, Gerrit

doi:10.3390/biom9120860

Cited by 18 publications

(19 citation statements)

References 193 publications

(259 reference statements)

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“…In contrast, mice heterozygous for the Pitx2 null allele and those in which the Pitx2 knockout was limited to NC cells were viable and displayed corneal, iris, and scleral defects similar to ARS in humans ( Chen and Gage, 2016 ). Retinoic acid is a known regulator of Pitx2 expression ( Bohnsack et al, 2012 ; Williams and Bohnsack, 2015 ; Chawla et al, 2016 ; Hebert et al, 2017 ; Draut et al, 2019 ; Williams and Bohnsack, 2019 ), but has differential effects depending on embryonic stage. During the early stages, retinoic acid decreases Pitx2 expression within NC cells migrating toward the pharyngeal arches.…”

Section: Ocular Neural Crest Derivatives: Lessons From Rare Ocular DImentioning

confidence: 99%

The Ocular Neural Crest: Specification, Migration, and Then What?

Williams

Bohnsack

2020

Front. Cell Dev. Biol.

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During vertebrate embryonic development, a population of dorsal neural tube-derived stem cells, termed the neural crest (NC), undergo a series of morphogenetic changes and extensive migration to become a diverse array of cell types. Around the developing eye, this multipotent ocular NC cell population, called the periocular mesenchyme (POM), comprises migratory mesenchymal cells that eventually give rise to many of the elements in the anterior of the eye, such as the cornea, sclera, trabecular meshwork, and iris. Molecular cell biology and genetic analyses of congenital eye diseases have provided important information on the regulation of NC contributions to this area of the eye. Nevertheless, a complete understanding of the NC as a contributor to ocular development remains elusive. In addition, positional information during ocular NC migration and the molecular pathways that regulate end tissue differentiation have yet to be fully elucidated. Further, the clinical challenges of ocular diseases, such as Axenfeld-Rieger syndrome (ARS), Peters anomaly (PA) and primary congenital glaucoma (PCG), strongly suggest the need for better treatments. While several aspects of NC evolution have recently been reviewed, this discussion will consolidate the most recent current knowledge on the specification, migration, and contributions of the NC to ocular development, highlighting the anterior segment and the knowledge obtained from the clinical manifestations of its associated diseases. Ultimately, this knowledge can inform translational discoveries with potential for sorely needed regenerative therapies.

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Section: Ocular Neural Crest Derivatives: Lessons From Rare Ocular DImentioning

confidence: 99%

The Ocular Neural Crest: Specification, Migration, and Then What?

Williams

Bohnsack

2020

Front. Cell Dev. Biol.

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“…Five of the differentially expressed TFs also had motifs which were significantly enriched in the differentially methylated regions; CDX1, MEOX2, HOXD8, FOXC1 and FOXD2 (Table S2). CDX1 is expressed in the limb bud and is responsive to retinoic acid (RA), WNT and FGF signals [30,31]. HOXD8 is expressed during early patterning in the proximal limb [8].…”

Section: Muscle Group Specific Dna Methylation and Gene Expression In Developmental Tfsmentioning

confidence: 99%

Muscle group specific transcriptomic and DNA methylation differences related to developmental patterning in FSHD

Williams

Kong

Nguyen

et al. 2021

Preprint

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Muscle groups throughout the body are specialized in function and are specified during development by position specific gene regulatory networks. In developed tissue, myopathies affect muscle groups differently. Facioscapulohumeral muscular dystrophy, FSHD, affects upper body and tibialis anterior (TA) muscles earlier and more severely than others such as quadriceps. To investigate an epigenetic basis for susceptibility of certain muscle groups to disease, we perform DNA methylation and RNA sequencing on primary patient derived myoblasts from TA and quadricep for both control and FSHD2 as well as RNA-seq for myoblasts from FSHD1 deltoid, bicep and TA over a time course of differentiation. We find that TA and quadricep retain methylation and expression differences in transcription factors that are key to muscle group specification during embryogenesis. FSHD2 patients have differences in DNA methylation and expression related to SMCHD1 mutations and FGF signaling. Genes induced specifically in FSHD are more highly expressed in commonly affected muscle groups. We find a set of genes that distinguish more susceptible muscle groups including development-associated TFs and genes involved in WNT signaling. Adult muscle groups therefore retain transcriptional and DNA methylation differences associated with development, which may contribute to susceptibility in FSHD.

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“…Retinoic acid (RA) signaling is one of the major regulatory pathways active during embryogenesis and it controls numerous developmental processes [1][2][3][4]. RA is produced in the body from nutritional sources containing vitamin A (retinol, ROL) and other retinoids, or carotenoids [5,6].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Loss of Retinoic Acid Network Genes in Xenopus laevis Achieves a Tighter Signal Regulation

Abbou

Bendelac-Kapon

Sebag

et al. 2022

Cells

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Retinoic acid (RA) is a major regulatory signal during embryogenesis produced from vitamin A (retinol) by an extensive, autoregulating metabolic and signaling network to prevent fluctuations that result in developmental malformations. Xenopus laevis is an allotetraploid hybrid frog species whose genome includes L (long) and S (short) chromosomes from the originating species. Evolutionarily, the X. laevis subgenomes have been losing either L or S homoeologs in about 43% of genes to generate singletons. In the RA network, out of the 47 genes, about 47% have lost one of the homoeologs, like the genome average. Interestingly, RA metabolism genes from storage (retinyl esters) to retinaldehyde production exhibit enhanced gene loss with 75% singletons out of 28 genes. The effect of this gene loss on RA signaling autoregulation was studied. Employing transient RA manipulations, homoeolog gene pairs were identified in which one homoeolog exhibits enhanced responses or looser regulation than the other, while in other pairs both homoeologs exhibit similar RA responses. CRISPR/Cas9 targeting of individual homoeologs to reduce their activity supports the hypothesis where the RA metabolic network gene loss results in tighter network regulation and more efficient RA robustness responses to overcome complex regulation conditions.

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New Insights into the Control of Cell Fate Choices and Differentiation by Retinoic Acid in Cranial, Axial and Caudal Structures

Cited by 18 publications

References 193 publications

The Ocular Neural Crest: Specification, Migration, and Then What?

The Ocular Neural Crest: Specification, Migration, and Then What?

Muscle group specific transcriptomic and DNA methylation differences related to developmental patterning in FSHD

Enhanced Loss of Retinoic Acid Network Genes in Xenopus laevis Achieves a Tighter Signal Regulation

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