scholarly journals Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis

2017 ◽  
Vol 4 (4) ◽  
pp. 160913 ◽  
Author(s):  
Nicoletta Carucci ◽  
Emanuele Cacci ◽  
Paola S. Nisi ◽  
Valerio Licursi ◽  
Yu-Lee Paul ◽  
...  

During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals.

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 105-122 ◽  
Author(s):  
Marysia Placzek ◽  
Toshiya Yamada ◽  
Marc Tessier-Lavigne ◽  
Thomas Jessell ◽  
Jane Dodd

Distinct classes of neural cells differentiate at specific locations within the embryonic vertebrate nervous system. To define the cellular mechanisms that control the identity and pattern of neural cells we have used a combination of functional assays and antigenic markers to examine the differentiation of cells in the developing spinal cord and hindbrain in vivo and in vitro. Our results suggest that a critical step in the dorsoventral patterning of the embryonic CNS is the differentiation of a specialized group of midline neural cells, termed the floor plate, in response to local inductive signals from the underlying notochord. The floor plate and notochord appear to control the pattern of cell types that appear along the dorsoventral axis of the neural tube. The fate of neuroepithelial cells in the ventral neural tube may be defined by cell position with respect to the ventral midline and controlled by polarizing signals that originate from the floor plate and notochord.


2021 ◽  
Vol 12 ◽  
Author(s):  
Huihui Wang ◽  
Chengliang Zhou ◽  
Min Hou ◽  
Hefeng Huang ◽  
Yun Sun

High maternal estradiol is reported to induce metabolic disorders by modulating hypothalamic gene expression in offspring. Since neurogenesis plays a crucial role during hypothalamus development, we explored whether prenatal high estradiol exposure (HE) affects proliferation and differentiation of fetal hypothalamic neural stem/progenitor cells (NSC/NPCs) in mice and performed RNA sequencing to identify the critical genes involved. NSC/NPCs in HE mice presented attenuated cell proliferation but increased neuronal differentiation in vitro compared with control (NC) cells. Gene set enrichment analysis of mRNA profiles indicated that genes downregulated in HE NSC/NPCs were enriched in neurogenesis-related Gene Ontology (GO) terms, while genes upregulated in HE NSC/NPCs were enriched in response to estradiol. Protein-protein interaction analysis of genes with core enrichment in GO terms of neurogenesis and response to estradiol identified 10 Hub mRNAs, among which three were potentially correlated with six differentially expressed (DE) lncRNAs based on lncRNA profiling and co-expression analysis. These findings offer important insights into developmental modifications in hypothalamic NSC/NPCs and may provide new clues for further investigation on maternal environment programmed neural development disorders.


Development ◽  
1992 ◽  
Vol 116 (1) ◽  
pp. 55-66 ◽  
Author(s):  
M. Wagner ◽  
B. Han ◽  
T.M. Jessell

Retinoic acid and related retinoids have been suggested to contribute to the pattern of cell differentiation during vertebrate embryonic development. To identify cell groups that release morphogenetically active retinoids, we have developed a reporter assay that makes use of a retinoic acid inducible response element (RARE) to drive lacZ or luciferase reporter genes in stably transfected cell lines. This reporter gene assay allows detection of retinoids released from embryonic tissues over a range equivalent to that induced by femtomole amounts of retinoic acid. We have used this assay first to determine whether the floor plate, a cell group that has polarizing properties in neural tube and limb bud differentiation, is a local source of retinoids within the spinal cord. We have also examined whether the effects of exogenously administered retinoic acid on anteroposterior patterning of cells in the developing central nervous system correlate with differences in retinoid release from anterior and posterior neural tissue. We find that the release of morphogenetically active retinoids from the floor plate is only about 1.5-fold that of the dorsal spinal cord, which does not have neural tube or limb polarizing activity. These results suggest that the spatial distribution of retinoid release from spinal cord tissues differs from that of the neural and limb polarizing activity. This assay has also shown that retinoids are released from the embryonic spinal cord at much greater levels than from the forebrain. This result, together with previous observations that the development of forebrain structures is suppressed by low concentrations of retinoic acid, suggest that the normal development of forebrain structures is dependent on the maintenance of low concentrations of retinoids in anterior regions of the embryonic axis. This assay has also provided initial evidence that other embryonic tissues with polarizing properties in vivo release retinoids in vitro.


Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 233-245 ◽  
Author(s):  
A. Graham ◽  
I. Heyman ◽  
A. Lumsden

Neural crest cells originate at three discontinuous levels along the rostrocaudal axis of the chick rhombencephalon, centred on rhombomeres 1 and 2, 4 and 6, respectively. These are separated by the odd-numbered rhombomeres r3 and r5 which are depleted of migratory neural crest cells. Here we show elevated levels of apoptosis in the dorsal midline of r3 and r5, immediately following the formation of these rhombomeres at the developmental stage (10–12) when neural crest cells would be expected to emerge at these neuraxial levels. These regions are also marked by their expression of members of the msx family of homeobox genes with msx-2 expression preceding apoptosis in a precisely colocalised pattern. In vitro and in ovo experiments have revealed that r3 and r5 are depleted of neural crest cells by an interaction within the neural epithelium: if isolated or distanced from their normal juxtaposition with even-numbered rhombomeres, both r3 and r5 produce migrating neural crest cells. When r3 or r5 are unconstrained in this way, allowing production of crest, msx-2 expression is concomitantly down regulated. This suggests a correlation between msx-2 and the programming of apoptosis in this system. The hindbrain neural crest is thus produced in discrete streams by mechanisms intrinsic to the neural epithelium. The crest cells that enter the underlying branchial region are organised into streams before they encounter the mesodermal environment lateral to the neural tube. This contrasts sharply with the situation in the trunk where neural crest production is uninterrupted along the neuraxis and the segmental accumulation of neurogenic crest cells is subsequently founded on an alternation of permissive and non-permissive qualities of the local mesodermal environment.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi-Fan Wang ◽  
Cong Liu ◽  
Peng-Fei Xu

AbstractOrganoid has become a novel in vitro model to research human development and relevant disorders in recent years. With many improvements on the culture protocols, current brain organoids could self-organize into a complicated three-dimensional organization that mimics most of the features of the real human brain at the molecular, cellular, and further physiological level. However, lacking positional information, an important characteristic conveyed by gradients of signaling molecules called morphogens, leads to the deficiency of spatiotemporally regulated cell arrangements and cell–cell interactions in the brain organoid development. In this review, we will overview the role of morphogen both in the vertebrate neural development in vivo as well as the brain organoid culture in vitro, the strategies to apply morphogen concentration gradients in the organoid system and future perspectives of the brain organoid technology.


2007 ◽  
Vol 27 (1) ◽  
pp. 45-52
Author(s):  
Koh-ichi Atoh ◽  
Manae S. Kurokawa ◽  
Hideshi Yoshikawa ◽  
Chieko Masuda ◽  
Erika Takada ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 91
Author(s):  
Verena Schultz ◽  
Stephanie L. Cumberworth ◽  
Quan Gu ◽  
Natasha Johnson ◽  
Claire L. Donald ◽  
...  

Understanding how Zika virus (Flaviviridae; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination—which is critical for saltatory conduction and neuronal function—has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.


2015 ◽  
Vol 36 (6) ◽  
pp. 913-922 ◽  
Author(s):  
Nallani Vijay Kumar ◽  
Jianbo Yang ◽  
Jitesh K. Pillai ◽  
Swati Rawat ◽  
Carlos Solano ◽  
...  

The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeastSaccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)]in vitroandin vivoand that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation.


Development ◽  
2010 ◽  
Vol 137 (16) ◽  
pp. 2795-2804 ◽  
Author(s):  
A. Porcher ◽  
A. Abu-Arish ◽  
S. Huart ◽  
B. Roelens ◽  
C. Fradin ◽  
...  

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