scholarly journals Retinoic Acid and Pitx2 Regulate Early Neural Crest Survival and Migration in Craniofacial and Ocular Development

2016 ◽  
Vol 107 (3) ◽  
pp. 126-135 ◽  
Author(s):  
Bahaar Chawla ◽  
Elisa Schley ◽  
Antionette L. Williams ◽  
Brenda L. Bohnsack
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Ocular Development ◽  
And Migration

Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos

Development ◽  
1991 ◽  
Vol 111 (1) ◽  
pp. 45-60 ◽  
Author(s):  
E. Ruberte ◽  
P. Dolle ◽  
P. Chambon ◽  
G. Morriss-Kay
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Binding Proteins ◽  
Primitive Streak ◽  
Distribution Patterns ◽  
Floor Plate ◽  
Mouse Embryos ◽  
Retinoic Acid Receptors ◽  
And Migration ◽  
Crest Cell

In situ hybridization with 35S-labelled RNA probes was used to study the distribution of transcripts of genes coding for the retinoic acid receptors, RAR-alpha, -beta and -gamma, and the cellular binding proteins for retinoic acid (CRABP I) and retinol (CRBP I), in mouse embryos during the period of early morphogenesis. Primary mesenchyme formation was associated with CRBP I labelling of both epiblast and mesenchyme of the primitive streak, while the CRABP probe labelled the migrating primary mesenchyme cells. Neural crest cell emigration and migration were associated with CRABP labelling of both neural epithelium (excluding the floor plate) and neural crest cells, while CRBP I expression was restricted to basal and apical regions of the epithelium (excluding the floor plate). The strongest neuroepithelial signal for CRABP was in the preoptic hindbrain. RAR-beta was present in presomitic stage embryos, being expressed at highest levels in the lateral regions. RAR-alpha was associated with crest cell emigration and migration, while RAR-gamma was present in the primitive streak region throughout the period of neurulation. There was a change from RAR-beta to RAR-gamma expression at the junction between closed and open neural epithelium at the caudal neuropore. RAR-alpha and RAR-beta were expressed at specific levels of the hindbrain and in the spinal cord. These distribution patterns are discussed in relation to segmental expression patterns of other genes, and to maturational changes in the caudal neuropore region. The CRABP transcript distribution patterns correlated well with known target tissues of excess retinoid-induced teratogenesis (migrating primary mesenchyme and neural crest cells, preoptic hindbrain), providing further support for our hypothesis that cells expressing CRABP are those that cannot tolerate high levels of RA for their normal developmental function.

Key roles of retinoic acid receptors alpha and beta in the patterning of the caudal hindbrain, pharyngeal arches and otocyst in the mouse

Development ◽  
1999 ◽  
Vol 126 (22) ◽  
pp. 5051-5059 ◽  
Author(s):  
V. Dupe ◽  
N.B. Ghyselinck ◽  
O. Wendling ◽  
P. Chambon ◽  
M. Mark
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Cranial Nerves ◽  
Detectable Effect ◽  
Expression Domain ◽  
Pharyngeal Arches ◽  
Double Mutation ◽  
And Migration ◽  
Mouse Fetuses ◽  
Early Developmental

Mouse fetuses carrying targeted inactivations of both the RAR(α) and the RARbeta genes display a variety of malformations in structures known to be partially derived from the mesenchymal neural crest originating from post-otic rhombomeres (e.g. thymus and great cephalic arteries) (Ghyselinck, N., Dupe, V., Dierich, A., Messaddeq, N., Garnier, J.M., Rochette-Egly, C., Chambon, P. and Mark M. (1997). Int. J. Dev. Biol. 41, 425–447). In a search for neural crest defects, we have analysed the rhombomeres, cranial nerves and pharyngeal arches of these double null mutants at early embryonic stages. The mutant post-otic cranial nerves are disorganized, indicating that RARs are involved in the patterning of structures derived from neurogenic neural crest, even though the lack of RARalpha and RARbeta has no detectable effect on the number and migration path of neural crest cells. Interestingly, the double null mutation impairs early developmental processes known to be independent of the neural crest e.g., the initial formation of the 3rd and 4th branchial pouches and of the 3rd, 4th and 6th arch arteries. The double mutation also results in an enlargement of rhombomere 5, which is likely to be responsible for the induction of supernumerary otic vesicles, in a disappearance of the rhombomere 5/6 boundary, and in profound alterations of rhombomere identities. In the mutant hindbrain, the expression domain of kreisler is twice its normal size and the caudal stripe of Krox-20 extends into the presumptive rhombomeres 6 and 7 region. In this region, Hoxb-1 is ectopically expressed, Hoxb-3 is ectopically up-regulated and Hoxd-4 expression is abolished. These data, which indicate that retinoic acid signaling through RARalpha and/or RARbeta is essential for the specification of rhombomere identities and for the control of caudal hindbrain segmentation by restricting the expression domains of kreisler and of Krox-20, also strongly suggest that this signaling plays a crucial role in the posteriorization of the hindbrain neurectoderm.

scholarly journals Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest

2020 ◽  
Vol 15 (3) ◽  
pp. 557-565
Author(s):  
Thomas J.R. Frith ◽  
Antigoni Gogolou ◽  
James O.S. Hackland ◽  
Zoe A. Hewitt ◽  
Harry D. Moore ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Neural Progenitors

scholarly journals Cadherin-6B proteolysis promotes the neural crest cell epithelial-to-mesenchymal transition through transcriptional regulation

2016 ◽  
Vol 215 (5) ◽  
pp. 735-747 ◽  
Author(s):  
Andrew T. Schiffmacher ◽  
Vivien Xie ◽  
Lisa A. Taneyhill
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cell ◽  
Cranial Neural Crest ◽  
Mesenchymal Transition ◽  
Effector Genes ◽  
A Disintegrin And Metalloproteinase ◽  
And Migration ◽  
Cranial Neural Crest Cells

During epithelial-to-mesenchymal transitions (EMTs), cells disassemble cadherin-based junctions to segregate from the epithelia. Chick premigratory cranial neural crest cells reduce Cadherin-6B (Cad6B) levels through several mechanisms, including proteolysis, to permit their EMT and migration. Serial processing of Cad6B by a disintegrin and metalloproteinase (ADAM) proteins and γ-secretase generates intracellular C-terminal fragments (CTF2s) that could acquire additional functions. Here we report that Cad6B CTF2 possesses a novel pro-EMT role by up-regulating EMT effector genes in vivo. After proteolysis, CTF2 remains associated with β-catenin, which stabilizes and redistributes both proteins to the cytosol and nucleus, leading to up-regulation of β-catenin, CyclinD1, Snail2, and Snail2 promoter-based GFP expression in vivo. A CTF2 β-catenin–binding mutant, however, fails to alter gene expression, indicating that CTF2 modulates β-catenin–responsive EMT effector genes. Notably, CTF2 association with the endogenous Snail2 promoter in the neural crest is β-catenin dependent. Collectively, our data reveal how Cad6B proteolysis orchestrates multiple pro-EMT regulatory inputs, including CTF2-mediated up-regulation of the Cad6B repressor Snail2, to ensure proper cranial neural crest EMT.

scholarly journals 03-P132 Xenopus HMGA2 is required for neural crest cell survival and migration

2009 ◽  
Vol 126 ◽  
pp. S106
Author(s):  
Simone Macrí ◽  
Marco Onorati ◽  
Guidalberto Manfioletti ◽  
Robert Vignali
Keyword(s):  
Neural Crest ◽  
Cell Survival ◽  
Neural Crest Cell ◽  
And Migration ◽  
Crest Cell

Temporally-regulated retinoic acid depletion produces specific neural crest, ocular and nervous system defects

Development ◽  
1997 ◽  
Vol 124 (16) ◽  
pp. 3111-3121 ◽  
Author(s):  
E.D. Dickman ◽  
C. Thaller ◽  
S.M. Smith
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Neural Crest ◽  
Female Rats ◽  
Retinoid Receptor ◽  
Knock Out ◽  
The Face ◽  
Normal Males ◽  
Temporal Events ◽  
Null Mutant Mice

Both retinoid receptor null mutants and classic nutritional deficiency studies have demonstrated that retinoids are essential for the normal development of diverse embryonic structures (e.g. eye, heart, nervous system, urogenital tract). Detailed analysis of retinoid-modulated events is hampered by several limitations of these models, including that deficiency or null mutation is present throughout gestation, making it difficult to isolate primary effects, and preventing analysis beyond embryolethality. We developed a mammalian model in which retinoid-dependent events are documented during distinct targeted windows of embryogenesis. This was accomplished through the production of vitamin A-depleted (VAD) female rats maintained on sufficient oral retinoic acid (RA) for growth and fertility. After mating to normal males, these RA-sufficient/VAD females were given oral RA doses which allowed for gestation in an RA-sufficient state; embryogenesis proceeded normally until retinoids were withdrawn dietarily to produce a sudden, acute retinoid deficiency during a selected gestational window. In this trial, final RA doses were administered on E11.5, vehicle at E12.5, and embryos analyzed on E13.5; during this 48 hour window, the last RA dose was metabolized and embryos progressed in a retinoid-deficient state. RA-sufficient embryos were normal. Retinoid-depleted embryos exhibited specific malformations of the face, neural crest, eyes, heart, and nervous system. Some defects were phenocopies of those seen in null mutant mice for RXR alpha(−/−), RXR alpha(−/−)/RAR alpha(−/−), and RAR alpha(−/−)/RAR gamma(−/−), confirming that RA transactivation of its nuclear receptors is essential for normal embryogenesis. Other defects were unique to this deficiency model, showing that complete ligand ‘knock-out’ is required to see those retinoid-dependent events previously concealed by receptor functional redundancy, and reinforcing that retinoid receptors have separate yet overlapping contributions in the embryo. This model allows for precise targeting of retinoid form and deficiency to specific developmental windows, and will facilitate studies of distinct temporal events.

Retinoid-binding protein distribution in the developing mammalian nervous system

Development ◽  
1990 ◽  
Vol 109 (1) ◽  
pp. 75-80 ◽  
Author(s):  
M. Maden ◽  
D.E. Ong ◽  
F. Chytil
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Neural Crest ◽  
Motor Neurons ◽  
Neural Tube ◽  
Binding Protein ◽  
Sympathetic Ganglia ◽  
Retinol Binding Protein ◽  
Otic Vesicle ◽  
Protein Distribution

We have analysed the distribution of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) in the day 8.5-day 12 mouse and rat embryo. CRBP is localised in the heart, gut epithelium, notochord, otic vesicle, sympathetic ganglia, lamina terminalis of the brain, and, most strikingly, in a ventral stripe across the developing neural tube in the future motor neuron region. This immunoreactivity remains in motor neurons and, at later stages, motor axons are labelled in contrast to unlabelled sensory axons. CRABP is localised to the neural crest cells, which are particularly noticeable streaming into the branchial arches. At later stages, neural crest derivatives such as Schwann cells, cells in the gut wall and sympathetic ganglia are immunoreactive. An additional area of CRABP-positive cells are neuroblasts in the mantle layer of the neural tube, which subsequently appear to be the axons and cell bodies of the commissural system. Since retinol and retinoic acid are the endogenous ligands for these binding proteins, we propose that retinoids may play a role in the development and differentiation of the mammalian nervous system and may interact with certain homoeobox genes whose transcripts have also been localised within the nervous system.

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