Expression of AmphiHox-1 and AmphiPax-1 in amphioxus embryos treated with retinoic acid: insights into evolution and patterning of the chordate nerve cord and pharynx

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1829-1838 ◽  
Author(s):  
L.Z. Holland ◽  
N.D. Holland
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Nerve Cord ◽  
Hox Genes ◽  
Expression Patterns ◽  
Expression Domain ◽  
Craniofacial Malformations ◽  
Pharyngeal Arches ◽  
Pharyngeal Endoderm ◽  
Cerebral Vesicle

Excess all-trans retinoic acid (RA) causes severe craniofacial malformations in vertebrate embryos: pharyngeal arches are fused or absent, and a rostrad expansion of Hoxb-1 expression in the hindbrain shows that anterior rhombomeres are homeotically respecified to a more posterior identity. As a corollary, neural crest migration into the pharyngeal arches is abnormal. We administered excess RA to developing amphioxus, the closest invertebrate relative of the vertebrates and thus a key organism for understanding evolution of the vertebrate body plan. In normal amphioxus, the nerve cord has only a slight anterior swelling, the cerebral vesicle, and apparently lacks migratory neural crest. Nevertheless, excess RA similarly affects amphioxus and vertebrates. The expression domain of AmphiHox-1 (homologous to mouse Hoxb-1) in the amphioxus nerve cord is also extended anteriorly. For both the amphioxus and mouse genes, excess RA causes either (1) continuous expression throughout the preotic hindbrain (mouse) and from the level of somite 7 to the anterior end of the nerve cord (amphioxus) or (2) discontinuous expression with a gap in rhombomere 3 (mouse) and a gap at the posterior end of the cerebral vesicle (amphioxus). A comparison of these expression patterns suggests that amphioxus has a homolog of the vertebrate hindbrain, both preotic and postotic. Although RA alters the expression of AmphiHox-1 expression in the amphioxus nerve cord, it does not alter the expression of AmphiHox-1 in presomitic mesoderm or of alkali myosin light chain (AmphiMlc-alk) in somites, and the axial musculature and notochord develop normally. The most striking morphogenetic effect of RA on amphioxus larvae is the failure of mouth and gill slits to form. In vertebrates effects of excess RA on pharyngeal development have been attributed solely to the abnormal migratory patterns of Hox-expressing cranial neural crest cells. This cannot be true for amphioxus because of the lack of migratory neural crest. Furthermore, expression of Hox genes in pharyngeal tissues of amphioxus has not yet been detected. However, the absence of gill slits in RA-treated amphioxus embryos correlates with an RA-induced failure of AmphiPax-1 to become down-regulated in regions of pharyngeal endoderm that would normally fuse with the overlying ectoderm. In vertebrates, RA might similarly act via Pax-1/9, also expressed in pharyngeal endoderm, to impair pharyngeal patterning.

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 16p12.1 deletion orthologs are expressed in motile neural crest cells and are important for regulating craniofacial development in Xenopus laevis

2020 ◽  
Author(s):  
Micaela Lasser ◽  
Jessica Bolduc ◽  
Luke Murphy ◽  
Caroline O'Brien ◽  
Sangmook Lee ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Neural Crest ◽  
Expression Patterns ◽  
Copy Number Variants ◽  
Neural Crest Cell ◽  
Underlying Mechanism ◽  
Craniofacial Development ◽  
Pharyngeal Arches ◽  
Individual Gene ◽  
Vertebrate Model

Copy number variants (CNVs) associated with neurodevelopmental disorders are characterized by extensive phenotypic heterogeneity. In particular, one CNV was identified in a subset of children clinically diagnosed with intellectual disabilities (ID) that results in a hemizygous deletion of multiple genes at chromosome 16p12.1. In addition to ID, individuals with this deletion display a variety of symptoms including microcephaly, seizures, cardiac defects, and growth retardation. Moreover, patients also manifest severe craniofacial abnormalities, such as micrognathia, cartilage malformation of the ears and nose, and facial asymmetries; however, the function of the genes within the 16p12.1 region have not been studied in the context of vertebrate craniofacial development. The craniofacial tissues affected in patients with this deletion all derive from the same embryonic precursor, the cranial neural crest, leading to the hypothesis that one or more of the 16p12.1 genes may be involved in regulating neural crest cell (NCC)-related processes. To examine this, we characterized the developmental role of the 16p12.1-affected gene orthologs, polr3e, mosmo, uqcrc2, and cdr2, during craniofacial morphogenesis in the vertebrate model system, Xenopus laevis. While the currently-known cellular functions of these genes are diverse, we find that they share similar expression patterns along the neural tube, pharyngeal arches, and later craniofacial structures. As these genes show co-expression in the pharyngeal arches where NCCs reside, we sought to elucidate the effect of individual gene depletion on craniofacial development and NCC migration. We find that reduction of several 16p12.1 genes significantly disrupts craniofacial and cartilage formation, pharyngeal arch migration, as well as NCC specification and motility. Thus, we have determined that some of these genes play an essential role during vertebrate craniofacial patterning by regulating specific processes during NCC development, which may be an underlying mechanism contributing to the craniofacial defects associated with the 16p12.1 deletion.

A genetic link between Tbx1 and fibroblast growth factor signaling

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4605-4611 ◽  
Author(s):  
Francesca Vitelli ◽  
Ilaria Taddei ◽  
Masae Morishima ◽  
Erik N. Meyers ◽  
Elizabeth A. Lindsay ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Expression Patterns ◽  
Pharyngeal Arch ◽  
Growth Factor Signaling ◽  
Expression Domain ◽  
Primary Defect ◽  
Genetic Link ◽  
Pharyngeal Endoderm ◽  
Pharyngeal Arch Arteries ◽  
Tbx1 Haploinsufficiency

Tbx1 haploinsufficiency causes aortic arch abnormalities in mice because of early growth and remodeling defects of the fourth pharyngeal arch arteries. The function of Tbx1 in the development of these arteries is probably cell non-autonomous, as the gene is not expressed in structural components of the artery but in the surrounding pharyngeal endoderm. We hypothesized that Tbx1 may trigger signals from the pharyngeal endoderm directed to the underlying mesenchyme. We show that the expression patterns of Fgf8 and Fgf10, which partially overlap with Tbx1 expression pattern, are altered in Tbx1–/– mutants. In particular, Fgf8 expression is abolished in the pharyngeal endoderm. To understand the significance of this finding for the pathogenesis of the mutant Tbx1 phenotype, we crossed Tbx1 and Fgf8 mutants. Double heterozygous Tbx1+/–;Fgf8+/– mutants present with a significantly higher penetrance of aortic arch artery defects than do Tbx1+/–;Fgf8+/+ mutants, while Tbx1+/+;Fgf8+/– animals are normal. We found that Fgf8 mutation increases the severity of the primary defect caused by Tbx1 haploinsufficiency, i.e. early hypoplasia of the fourth pharyngeal arch arteries, consistent with the time and location of the shared expression domain of the two genes. Hence, Tbx1 and Fgf8 interact genetically in the development of the aortic arch. Our data provide the first evidence of a genetic link between Tbx1 and FGF signaling, and the first example of a modifier of the Tbx1 haploinsufficiency phenotype. We speculate that the FGF8 locus might affect the penetrance of cardiovascular defects in individuals with chromosome 22q11 deletions involving TBX1.

Retinoic acid synthesis and hindbrain patterning in the mouse embryo

Development ◽  
2000 ◽  
Vol 127 (1) ◽  
pp. 75-85 ◽  
Author(s):  
K. Niederreither ◽  
J. Vermot ◽  
B. Schuhbaur ◽  
P. Chambon ◽  
P. Dolle
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Hox Genes ◽  
Receptor Gene ◽  
Acid Synthesis ◽  
Branchial Arch ◽  
Eph Receptor ◽  
Caudal Portion ◽  
Midbrain Region ◽  
Broad Domain

Targeted disruption of the murine retinaldehyde dehydrogenase 2 (Raldh2) gene precludes embryonic retinoic acid (RA) synthesis, leading to midgestational lethality (Niederreither, K., Subbarayan, V., Dolle, P. and Chambon, P. (1999). Nature Genet. 21, 444–448). We describe here the effects of this RA deficiency on the development of the hindbrain and associated neural crest. Morphological segmentation is impaired throughout the hindbrain of Raldh2−/− embryos, but its caudal portion becomes preferentially reduced in size during development. Specification of the midbrain region and of the rostralmost rhombomeres is apparently normal in the absence of RA synthesis. In contrast, marked alterations are seen throughout the caudal hindbrain of mutant embryos. Instead of being expressed in two alternate rhombomeres (r3 and r5), Krox20 is expressed in a single broad domain, correlating with an abnormal expansion of the r2-r3 marker Meis2. Instead of forming a defined r4, Hoxb1- and Wnt8A-expressing cells are scattered throughout the caudal hindbrain, whereas r5/r8 markers such as kreisler or group 3/4 Hox genes are undetectable or markedly downregulated. Lack of alternate Eph receptor gene expression could explain the failure to establish rhombomere boundaries. Increased apoptosis and altered migratory pathways of the posterior rhombencephalic neural crest cells are associated with impaired branchial arch morphogenesis in mutant embryos. We conclude that RA produced by the embryo is required to generate posterior cell fates in the developing mouse hindbrain, its absence leading to an abnormal r3 (and, to a lesser extent, r4) identity of the caudal hindbrain cells.

sucker encodes a zebrafish Endothelin-1 required for ventral pharyngeal arch development

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3815-3828 ◽  
Author(s):  
C.T. Miller ◽  
T.F. Schilling ◽  
K. Lee ◽  
J. Parker ◽  
C.B. Kimmel
Keyword(s):  
Neural Crest ◽  
Expression Patterns ◽  
Neural Crest Cells ◽  
Paraxial Mesoderm ◽  
Dorsoventral Patterning ◽  
Surface Ectoderm ◽  
Pharyngeal Arches ◽  
Endothelin 1 ◽  
Lower Jaw ◽  
Arch Neural

Mutation of sucker (suc) disrupts development of the lower jaw and other ventral cartilages in pharyngeal segments of the zebrafish head. Our sequencing, cosegregation and rescue results indicate that suc encodes an Endothelin-1 (Et-1). Like mouse and chick Et-1, suc/et-1 is expressed in a central core of arch paraxial mesoderm and in arch epithelia, both surface ectoderm and pharyngeal endoderm, but not in skeletogenic neural crest. Long before chondrogenesis, suc/et-1 mutant embryos have severe defects in ventral arch neural crest expression of dHAND, dlx2, msxE, gsc, dlx3 and EphA3 in the anterior arches. Dorsal expression patterns are unaffected. Later in development, suc/et-1 mutant embryos display defects in mesodermal and endodermal tissues of the pharynx. Ventral premyogenic condensations fail to express myoD, which correlates with a ventral muscle defect. Further, expression of shh in endoderm of the first pharyngeal pouch fails to extend as far laterally as in wild types. We use mosaic analyses to show that suc/et-1 functions nonautonomously in neural crest cells, and is thus required in the environment of postmigratory neural crest cells to specify ventral arch fates. Our mosaic analyses further show that suc/et-1 nonautonomously functions in mesendoderm for ventral arch muscle formation. Collectively our results support a model for dorsoventral patterning of the gnathostome pharyngeal arches in which Et-1 in the environment of the postmigratory cranial neural crest specifies the lower jaw and other ventral arch fates.

scholarly journals Serotonin is required for pharyngeal arch morphogenesis in zebrafish

2014 ◽  
Author(s):  
Katarina Kotnik Halavaty ◽  
Michael Bader ◽  
Saleh Bashammakh ◽  
Salim Seyfried
Keyword(s):  
Neural Crest ◽  
Tryptophan Hydroxylase ◽  
Expression Patterns ◽  
Pharyngeal Arch ◽  
Pharyngeal Arches ◽  
Early Markers ◽  
Morpholino Oligonucleotides ◽  
Antisense Morpholino Oligonucleotides ◽  
Induced Defects

Serotonin (5-HT) is not only a neurotransmitter but also a mediator of developmental processes in vertebrates. In this study, we analyzed the importance of 5-HT during zebrafish development. The expression patterns of three zebrafish tryptophan hydroxylase isoforms (Tph1A, Tph1B, Tph2), the rate-limiting enzymes in 5-HT synthesis, were analyzed and compared to the appearance and distribution of 5-HT. 5-HT was found in the raphe nuclei correlating with tph2 expression and in the pineal gland correlating with tph1a and tph2 expression. tph2 deficient fish generated with antisense morpholino oligonucleotides exhibited morphogenesis defects during pharyngeal arch development. The correct specification of neural crest cells was not affected in tph2 morphants as shown by the expression of early markers, but the survival and differentiation of pharyngeal arch progenitor cells were impaired. An organizing role of 5-HT in pharyngeal arch morphogenesis was suggested by a highly regular pattern of 5-HT positive cells in this tissue. Moreover, the 5-HT2B receptor was expressed in the pharyngeal arches and its pharmacological inhibition also induced defects in pharyngeal arch morphogenesis. These results support an important role of Tph2-derived serotonin as a morphogenetic factor in the development of neural crest derived tissues.

scholarly journals Characterisation of a dual-colour retinoic acid reporter system for analysing cells and embryos

2021 ◽  
Author(s):  
◽  
Bianca Black
Keyword(s):  
Retinoic Acid ◽  
Embryonic Development ◽  
Hox Genes ◽  
Fluorescent Proteins ◽  
Expression Patterns ◽  
Tissue Type ◽  
Cell Populations ◽  
Growth Media ◽  
Reporter System ◽  
Transgenic Mouse Line

<p>Vitamin A is an important component in the diet as its metabolites, the retinoids, play key roles in a vast range of cellular functions, from production of germ cells, to embryonic development and right through until adulthood. The function of retinoids, in particular retinoic acid (RA), is especially important during early embryonic development, where it is responsible for many different key developmental events. Some of the processes controlled by RA include brain region patterning, Hox gene expression, axis establishment and somite formation. Here, we aimed to characterise the expression pattern of retinoic acid in the early murine embryo and isolate cell populations from a range of RA concentrations to analyse the mRNA expression.  To do this, we used a transgenic mouse line which expressed a reporter plasmid that was able to show, through the expression of two fluorescent proteins, areas of high RA concentration and area of low RA concentration. We tested the function of this reporter system in vitro, using cell lines which were transfected with the plasmid and exposed to RA in their growth media. This worked showed a somewhat does-dependent response from the reporter system expressing the fluorescent proteins. We then imaged transgenic embryos at various stages of early development, to ascertain the areas of RA expression and repression. Here, we saw fluorescent protein expression patterns that indicated both high and low concetrations of RA. Using this information, we dissociated transgenic E8.5 embryos and sorted the cells based on their levels of expression of the two fluorescent proteins, as well as by tissue type, which had been marked with antibodies. mRNA was extracted from these populations and PCR was performed to identify the presence of Hox genes and to see any difference in expression patterns across the various cell populations.</p>

Sequence and developmental expression of AmphiDll, an amphioxus Distal-less gene transcribed in the ectoderm, epidermis and nervous system: insights into evolution of craniate forebrain and neural crest

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2911-2920 ◽  
Author(s):  
N.D. Holland ◽  
G. Panganiban ◽  
E.L. Henyey ◽  
L.Z. Holland
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Expression Patterns ◽  
Neural Plate ◽  
Epidermal Cells ◽  
Developmental Expression ◽  
Neural Cells ◽  
Dorsoventral Axis ◽  
Dynamic Expression ◽  
Cerebral Vesicle

The dynamic expression patterns of the single amphioxus Distal-less homolog (AmphiDll) during development are consistent with successive roles of this gene in global regionalization of the ectoderm, establishment of the dorsoventral axis, specification of migratory epidermal cells early in neurulation and the specification of forebrain. Such a multiplicity of Distal-less functions probably represents an ancestral chordate condition and, during craniate evolution, when this gene diversified into a family of six or so members, the original functions evidently tended to be parcelled out among the descendant genes. In the amphioxus gastrula, AmphiDll is expressed throughout the animal hemisphere (presumptive ectoderm), but is soon downregulated dorsally (in the presumptive neural plate). During early neurulation, AmphiDll-expressing epidermal cells flanking the neural plate extend lamellipodia, appear to migrate over it and meet mid-dorsally. Midway in neurulation, cells near the anterior end of the neural plate begin expressing AmphiDll and, as neurulation terminates, these cells are incorporated into the dorsal part of the neural tube, which forms by a curling of the neural plate. This group of AmphiDll-expressing neural cells and a second group expressing the gene a little later and even more anteriorly in the neural tube demarcate a region that comprises the anterior three/fourths of the cerebral vesicle; this region of the amphioxus neural tube, as judged by neural expression domains of craniate Distal-less-related genes, is evidently homologous to the craniate forebrain. Our results suggest that craniates evolved from an amphioxus-like creature that had the beginnings of a forebrain and possibly a precursor of neural crest - namely, the cell population leading the epidermal overgrowth of the neural plate during early neurulation.

scholarly journals A Retinoic Acid Responsive Hoxa3 Transgene Expressed in Embryonic Pharyngeal Endoderm, Cardiac Neural Crest and a Subdomain of the Second Heart Field

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27624 ◽  
Author(s):  
Nata Y. S.-G. Diman ◽  
Sophie Remacle ◽  
Nicolas Bertrand ◽  
Jacques J. Picard ◽  
Stéphane Zaffran ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Cardiac Neural Crest ◽  
Second Heart Field ◽  
Pharyngeal Endoderm ◽  
Heart Field

scholarly journals Endoderm Morphogenesis Reveals Integration of Distinct Processes in the Development and Evolution of Pharyngeal Arches

2018 ◽  
Author(s):  
Kazunori Okada ◽  
Hiroshi Wada ◽  
Shinji Takada
Keyword(s):  
Retinoic Acid ◽  
Comparative Analysis ◽  
Retinoic Acid Signaling ◽  
Pharyngeal Arches ◽  
Developmental Defects ◽  
Pharyngeal Endoderm ◽  
Development And Evolution

ABSTRACTThe vertebrate pharyngeal arches (PAs) are established by a combination of two styles of segmentation; the most anterior 2 PAs are simultaneously but the others are sequentially formed. However, the mechanism underlying their coexistence is unclear. Here, we show that the simultaneous and sequential segmentation discretely proceeded, respectively, but were finally integrated at the second PP (PP2), by dynamic morphogenesis of pharyngeal endoderm in the zebrafish. The coordination of these 2 distinct processes appears to be common in the PA development of many vertebrates, in which specific developmental defects posterior to the PP2 are caused by mutations of particular genes or perturbation of retinoic acid signaling. Surprisingly, comparative analysis of PA segmentation showed that the combinatorial styles of PA development is present in shark but not in lamprey, suggesting that PA segmentation was modified in the stem gnathostomes corresponding to the drastic pharyngeal innovations, such as PA2-derived opercular.

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