Retinoic acid signaling in spinal cord development

Lara-Ramírez, Ricardo; Zieger, Elisabeth; Schubert, Michael

doi:10.1016/j.biocel.2013.04.002

Cited by 34 publications

(37 citation statements)

References 158 publications

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“…The cells were differentiated to NPCs and transitioned towards an OL fate following a published protocol with some modifications (Douvaras and Fossati, 2015) (Figure 1A). PAX6, a classical marker for NPCs, was used to confirm the presence of NPCs at culture day 8 programmed either with Wnt-C59 (a Wnt pathway inhibitor, a driver of rostral CNS fate (Hermanto et al, 2019;Patapoutian and Reichardt, 2000)) or Retinoic Acid (RA, a driver of caudal CNS fate (Goldman and Kuypers, 2015;Lara-Ramírez et al, 2013)) (Figure 1F,G,H).…”

Section: Generation Of Pax6+ Npcs With Different Regional Characteristicsmentioning

confidence: 99%

Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs with Trisomy 21

Klein

Rampam

et al. 2021

Preprint

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SummaryThe intellectual disability found in people with Down syndrome (DS) is associated with a decrease in white matter in the central nervous system. To study the mechanism of this myelination deficit, we differentiated two isogenic lines of induced pluripotent stem cells (iPSCs) derived from people with DS into brain-like and spinal cord-like neural progenitor cells (NPCs) and promoted a transition towards oligodendroglial fate by activating the Sonic hedgehog (SHH) pathway. In the spinal cord-like trisomic cells, we found no difference in expression of OLIG2 or NKX2.2, two transcription factors essential for commitment to the oligodendrocyte (OL) lineage. However, in the brain-like trisomic NPCs, OLIG2 is significantly upregulated and is associated with reduced expression of NKX2.2. We found that this gene dysregulation and block in NPC transition can be normalized by increasing the concentration of a SHH pathway agonist (SAG) during differentiation. These results underscore the importance of regional and cell type differences in gene expression in DS and demonstrate that modulation of SHH signaling in trisomic cells can rescue an early perturbed step in neural lineage specification in DS.

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Section: Generation Of Pax6+ Npcs With Different Regional Characteristicsmentioning

confidence: 99%

Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs with Trisomy 21

Klein

Rampam

et al. 2021

Preprint

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“…Here, we found a ventral progenitor signature in which they express a unique set of transcription factors: sox21a, foxb1a, sp8a and dbx1a/1b. In addition, these cells express several signalling modulators: sfrp5 (soluble inhibitor of Wnt signalling), cyp26b1 (RA degradation), scube2 (Shh long-range signalling), and sulf2b (heparan sulfate proteoglycans) (Fig.3), which may contribute to modulation of Wnt, RA and Shh levels that underlie neuronal cell type specification (Dessaud et al, 2008; Lara-Ramirez et al, 2013; Lupo et al, 2006; Ulloa and Marti, 2010).…”

Section: Resultsmentioning

confidence: 99%

A single cell transcriptome atlas of the developing zebrafish hindbrain

Tambalo

Mitter

Wilkinson

2019

Preprint

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Segmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at bounderies and segment centres, in part mediated by Fgf20 signaling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.

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“…This study revealed that the recruitment of co-activators to the RAR/RXR heterodimers occurs at specific RAREs sites. The binding of the RAR/RXR heterodimer to RAREs, and recruitment of coactivators, leads to the transcription of retinoid target genes, for further detail please see [ 30 , 31 ] ( Figure 2 ).…”

Section: Retinoic Acid Signaling In Normal Cellsmentioning

confidence: 99%

Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies

Hunsu

Facey

Fields³

et al. 2021

IJMS

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Retinoic acid (RA) agents possess anti-tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X receptor (RXR), and their isoforms. The identification of mutations in retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. For example, chromosomal translocation involving RARA occurs in acute promyelocytic leukemia (APL), and all-trans retinoic acid (ATRA) is a highly effective and even curative therapeutic for APL patients. Thus, retinoid-based target discovery presents an important line of attack toward designing new, more effective strategies for treating other cancer types. Here, we review retinoid signaling, provide an update on retinoid agents and the current clinical research on retinoids in cancer, and discuss how the retinoid pathway genotype affects the ability of retinoid agents to inhibit the growth of colorectal cancer (CRC) cells. We also deliberate on why retinoid agents have not shown clinical efficacy against solid tumors and discuss alternative strategies that could overcome the lack of efficacy.

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Retinoic acid signaling in spinal cord development

Cited by 34 publications

References 158 publications

Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs with Trisomy 21

Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs with Trisomy 21

A single cell transcriptome atlas of the developing zebrafish hindbrain

Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies

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