Patterning the vertebrate head: murine Hox 2 genes mark distinct subpopulations of premigratory and migrating cranial neural crest

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 43-50 ◽  
Author(s):  
P. Hunt ◽  
D. Wilkinson ◽  
R. Krumlauf
Keyword(s):  
Neural Crest ◽  
Hox Genes ◽  
Positional Information ◽  
Branchial Arch ◽  
Neural Plate ◽  
Surface Ectoderm ◽  
Homologous Genes ◽  
The Face ◽  
Facial Pattern ◽  
Restricted Pattern

The structures of the face in vertebrates are largely derived from neural crest. There is some evidence to suggest that the form of the facial pattern is determined by the crest, and that it is specified before migration as to the structures that is is able to form. The neural crest is able to control the form of surrounding, non-neural crest tissues by an instructive interaction. Some of this cranial crest is derived from a region of the hindbrain that expresses Hox 2 homeobox genes in an overlapping and segment-restricted pattern. We have found that neurogenic and mesenchymal neural crest expresses Hox 2 genes from its point of origin beside the neural plate, during migration and after migration has ceased and that rhombomeres 3 and 5 do not have any expressing neural crest beside them. Each branchial arch expresses a different combination or code of Hox genes in a segment-restricted way. The surface ectoderm over the arches initially does not express Hox genes, and later adopts an expression pattern that reflects that of neural crest that has come to underlie it. We suggest that initially the neural plate and neural crest are spatially specified, while the surface ectoderm is unpatterned. Subsequently some positional information could be transferred to the surface ectoderm as a result of an interaction with the neural crest. Given that the role of the homologous genes in insects is position specification, and that neural crest is imprinted before migration, we suggest that Hox 2 genes are providing part of this positional information to the neural crest and hence are involved in patterning the structures of the branchial arches.

Is there a ventral neural ridge in chick embryos? Implications for the origin of adenohypophyseal and other APUD cells

Development ◽  
1980 ◽  
Vol 57 (1) ◽  
pp. 71-78
Author(s):  
N. B. Levy ◽  
Ann Andrew ◽  
B. B. Rawdon ◽  
Beverley Kramer
Keyword(s):  
Neural Crest ◽  
Endocrine Cells ◽  
Ventral Surface ◽  
Neural Plate ◽  
Chick Embryos ◽  
Serial Sections ◽  
Apud Cells ◽  
Surface Ectoderm ◽  
Neural Ectoderm ◽  
Thickened Surface

Two- to ten-somite chick embryos were studied in order to ascertain whether, as has been proposed, there exists a ‘ventral neural ridge’ which gives rise to the hypophyseal (Rathke's) pouch. Serial sections and stereo-microscopy were used. The neural ridges arch around the rostral end of the embryo onto the ventral surface of the head, but no evidence was found for their extension to form a ‘ventral neural ridge’ reaching the stomodaeum: in fact a considerable expanse of non-thickened surface ectoderm was seen to separate the ventral portions of the neural ridges from the stomodaeum. The thickening of neural ectoderm which does appear on the ventral surface of the head results from apposition and fusion of the opposite neural ridges flanking the neural plate and thus the tip of the anterior neuropore - the classically accepted mode of closure of the neuropore. These findings are in accord with the generally accepted concept of the origin of thehypophyseal pouch rather than with its derivation from a ‘ventral neural ridge’. No sign of neural crest formation was encountered ventrally; this observation excludes the possibility that endocrine cells of the APUD series could originate from neural crest in this region.

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.

Negative effect of Hox gene expression on the development of the neural crest-derived facial skeleton

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4301-4313 ◽  
Author(s):  
Sophie Creuzet ◽  
Gérard Couly ◽  
Christine Vincent ◽  
Nicole M. Le Douarin
Keyword(s):  
Gene Expression ◽  
Neural Crest ◽  
Hox Genes ◽  
Fluorescent Protein ◽  
Anterior Part ◽  
Distal Segment ◽  
Branchial Arch ◽  
Avian Embryo ◽  
Facial Skeleton ◽  
Hox Gene

Diencephalic, mesencephalic and metencephalic neural crest cells are skeletogenic and derive from neural folds that do not express Hox genes. In order to examine the influence of Hox gene expression on skull morphogenesis, expression of Hoxa2, Hoxa3 and Hoxb4 in conjunction with that of the green fluorescent protein has been selectively targeted to the Hox-negative neural folds of the avian embryo prior to the onset of crest cell emigration. Hoxa2 expression precludes the development of the entire facial skeleton. Transgenic Hoxa2 embryos such as those from which the Hox-negative domain of the cephalic neural crest has been removed have no upper or lower jaws and no frontonasal structures. Embryos subjected to the forced expression of Hoxa3 and Hoxb4 show severe defects in the facial skeleton but not a complete absence of facial cartilage. Hoxa3 prevents the formation of the skeleton derived from the first branchial arch, but allows the development (albeit reduced) of the nasal septum. Hoxb4, by contrast, hampers the formation of the nasal bud-derived skeleton, while allowing that of a proximal (but not distal) segment of the lower jaw. The combined effect of Hoxa3 and Hoxb4 prevents the formation of facial skeletal structures, comparable with Hoxa2. None of these genes impairs the formation of neural derivatives of the crest. These results suggest that over the course of evolution, the absence of Hox gene expression in the anterior part of the chordate embryo was crucial in the vertebrate phylum for the development of a face, jaws and brain case, and, hence, also for that of the forebrain.

Homeobox genes and models for patterning the hindbrain and branchial arches

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 187-196 ◽  
Author(s):  
Paul Hunt ◽  
Jenny Whiting ◽  
Ian Muchamore ◽  
Heather Marshall ◽  
Robb Krumlauf
Keyword(s):  
Gene Expression ◽  
Neural Crest ◽  
Expression Pattern ◽  
Hox Genes ◽  
Homeobox Genes ◽  
Neural Plate ◽  
The Body ◽  
Hox Gene ◽  
Hox Code ◽  
Branchial Region

Antennapedia class homeobox genes, which in insects are involved in regional specification of the segmented central regions of the body, have been implicated in a similar role in the vertebrate hindbrain. The development of the hindbrain involves the establishment of compartments which are subsequently made distinct from each other by Hox gene expression, implying that the lineage of neural cells may be an important factor in their development. The hindbrain produces the neural crest that gives rise to the cartilages of the branchial skeleton. Lineage also seems to be important in the neural crest, as experiments have shown that the crest will form cartilages appropriate to its level of origin when grafted to a heterotopic location. We show how the Hox genes could also be involved in patterning the mesenchymal structures of the branchial skeleton. Recently it has been proposed that the rhombomererestricted expression pattern of Hox 2 genes is the result of a tight spatially localised induction from underlying head mesoderm, in which a prepattern of Hox expression is visible. We find no evidence for this model, our data being consistent with the idea that the spatially localised expression pattern is a result of segmentation processes whose final stages are intrinsic to the neural plate. We suggest the following model for patterning in the branchial region. At first a segment-restricted code of Hox gene expression becomes established in the neuroepithelium and adjacent presumptive neural crest. This expression is then maintained in the neural crest during migration, resulting in a Hox code in the cranial ganglia and branchial mesenchyme that reflects the crest's rhombomere of origin. The final stage is the establishment of Hox 2 expression in the surface ectoderm which is brought into contact with neural crest-derived branchial mesenchyme. The Hox code of the branchial ectoderm is established later in development than that of the neural plate and crest, and involves the same combination of genes as the underlying crest. Experimental observations suggest the idea of an instructive interaction between branchial crest and its overlying ectoderm, which would be consistent with our observations. The distribution of clusters of Antennapedia class genes within the animal kingdom suggests that the primitive chordates ancestral to vertebrates had at least one Hox cluster. The origin of the vertebrates is thought to have been intimately linked to the appearance of the neural crest, initially in the branchial region. Our data are consistent with the idea that the branchial region of the head arose in evolution before the more anterior parts, the development of the branchial region employing the Hox genes in a more determinate patterning system. In this scenario, the anterior parts of the head arose subsequently, which may explain the greater importance of interactions in their development, and the fact that Antennapedia class Hox genes are not expressed there.

Hox genes, neural crest cells and branchial arch patterning

2001 ◽  
Vol 13 (6) ◽  
pp. 698-705 ◽  
Author(s):  
Paul A Trainor ◽  
Robb Krumlauf
Keyword(s):  
Neural Crest ◽  
Hox Genes ◽  
Neural Crest Cells ◽  
Branchial Arch

scholarly journals Making Headway: The Roles of Hox Genes and Neural Crest Cells in Craniofacial Development

2003 ◽  
Vol 3 ◽  
pp. 240-264 ◽  
Author(s):  
Paul A. Trainor
Keyword(s):  
Neural Crest ◽  
Hox Genes ◽  
Neural Crest Cell ◽  
Axial Skeleton ◽  
Craniofacial Development ◽  
Congenital Defects ◽  
Connective Tissues ◽  
Surface Ectoderm ◽  
Head Development ◽  
Tissue Interactions

Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development.

scholarly journals Hoxb3 Regulates Jag1 Expression in Pharyngeal Epithelium and Affects Interaction With Neural Crest Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Haoran Zhang ◽  
Junjie Xie ◽  
Karl Kam Hei So ◽  
Ka Kui Tong ◽  
Jearn Jang Sae-Pang ◽  
...  
Keyword(s):  
Neural Crest ◽  
Neural Crest Cells ◽  
Positional Information ◽  
Cell Types ◽  
Cellular Interaction ◽  
Pharyngeal Arch ◽  
Surface Ectoderm ◽  
Pharyngeal Arches ◽  
Elevated Expression ◽  
Pharyngeal Epithelium

Craniofacial morphogenesis depends on proper migration of neural crest cells and their interactions with placodes and other cell types. Hox genes provide positional information and are important in patterning the neural crest and pharyngeal arches (PAs) for coordinated formation of craniofacial structures. Hox genes are expressed in the surface ectoderm and epibranchial placodes, their roles in the pharyngeal epithelium and their downstream targets in regulating PA morphogenesis have not been established. We altered the Hox code in the pharyngeal region of the Hoxb3Tg/+ mutant, in which Hoxb3 is driven to ectopically expressed in Hoxb2 domain in the second pharyngeal arch (PA2). In the transgenic mutant, ectopic Hoxb3 expression was restricted to the surface ectoderm, including the proximal epibranchial placodal region and the distal pharyngeal epithelium. The Hoxb3Tg/+ mutants displayed hypoplasia of PA2, multiple neural crest-derived facial skeletal and nerve defects. Interestingly, we found that in the Hoxb3Tg/+ mutant, expression of the Notch ligand Jag1 was specifically up-regulated in the ectodermal pharyngeal epithelial cells of PA2. By molecular experiments, we demonstrated that Hoxb3 could bind to an upstream genomic site S2 and directly regulate Jag1 expression. In the Hoxb3Tg/+ mutant, elevated expression of Jag1 in the pharyngeal epithelium led to abnormal cellular interaction and deficiency of neural crest cells migrating into PA2. In summary, we showed that Hoxb3 regulates Jag1 expression and proposed a model of pharyngeal epithelium and neural crest interaction during pharyngeal arch development.

Spatial organization of the epithelium and the role of neural crest cells in the initiation of the mammalian tooth germ

Development ◽  
1988 ◽  
Vol 103 (Supplement) ◽  
pp. 155-169 ◽  
Author(s):  
A. G. S. Lumsden
Keyword(s):  
Neural Crest ◽  
Spatial Organization ◽  
Developmental Stages ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Limb Bud ◽  
Oral Epithelium ◽  
Cranial Neural Crest ◽  
Surface Ectoderm ◽  
Mandibular Arch

Teeth develop from composite organ rudiments that are formed through the interaction of oral epithelium and mesenchyme of the first branchial arch; cells of the former differentiate into enamel-secreting ameloblasts whereas those of the latter differentiate into dentine-secreting odontoblasts. Experimental analysis of odontogenic tissue interactions in mammalian embryos has focused on the late developmental stages of morphogenesis and cytodifferentiation; little is known about initial pattern-forming events, during which presumptive tooth-forming cells are specified and the sites of tooth initiation become established. It requires to be shown, for example, whether the mesenchymal cells of mammalian teeth are derived, like those of amphibians, from the cranial neural crest, and if so, whether these form a specified subpopulation in the neural folds. Alternatively, are they specified after migration into the mandibular arch, possibly by interaction with the oral epithelium? The developmental potentials of mouse embryo premigratory cranial neural crest cells (CNC – explanted from the caudal mesencephalic and rostral metencephalic neural folds) have been studied in intraocular homograft recombinations with various regions of embryonic surface ectoderm. Cartilage, bone and neural tissue developed in all combinations of CNC and epithelium. Teeth formed in combinations of CNC with mandibular arch epithelium but not in combinations of CNC with limb bud epithelium. Teeth also formed in combinations of mandibular arch epithelium with neural crest explanted from the trunk level. These results indicate that mammalian neural crest has an odontogenic potential but that this is not restricted to the crest of presumptive tooth-forming levels. Normal migration appears not to be a prerequisite for expression of odontogenic potential but this does require an interaction with region-specific epithelium. It is reasonable to infer that during normal development the neural crest that enters the mandibular arch is odontogenically unspecified before or during migration and that the oral epithelium is the earliest known site of tooth pattern.

Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm

Development ◽  
1990 ◽  
Vol 110 (2) ◽  
pp. 589-607 ◽  
Author(s):  
M.A. Frohman ◽  
M. Boyle ◽  
G.R. Martin
Keyword(s):  
Gene Expression ◽  
Neural Tube ◽  
Expression Patterns ◽  
Positional Information ◽  
Branchial Arch ◽  
Neural Plate ◽  
Specific Gene ◽  
Second Phase ◽  
Anterior Posterior ◽  
Rhombomere 4

It is rapidly becoming accepted that the vertebrate neural tube, in particular the hindbrain, develops into a segmented structure. After segment formation, cells in the neural tube do not cross segmental boundaries, and segment-specific gene expression is observed. However, it is not known what positional cues instruct the neural tube to express genes in this restricted manner. We have cloned a murine homeobox-containing gene, Hox-2.9, whose expression in the neural tube at E9.5 is restricted to a segment of the hindbrain known as rhombomere 4. A study of its expression pattern earlier in development revealed that prior to the start of neurulation (E7.5) Hox-2.9 is expressed within a posterior to the embryonic mesoderm that will participate in hindbrain formation. With the onset of neurulation, expression then becomes detectable in the neural plate as well, but only in the part that overlies the Hox-2.9-expressing mesoderm; it is not detected in the more anterior neuroectoderm that will form the future midbrain and forebrain. On the basis of these findings, we propose that the mesoderm is providing cues that serve to instruct the overlying neuroectoderm with respect to its position along the anteroposterior axis and that Hox-2.9 participates in or reflects this process. As neurulation continues and individual segments form, a second phase of expression is detected in the neural tube in which high levels of Hox-2.9 transcripts become restricted to rhombomere 4. Hox-2.9 expression is also detected in the developing branchial arch units of the hindbrain region, in a pattern that suggests to us that here, too, mesoderm is providing a localized signal that induces Hox-2.9 expression, in this case in endoderm of the pharynx and in superficial ectoderm. In general, we interpret the expression patterns of Hox-2.9 in the hindbrain region as suggesting that the specific mechanisms of pattern formation in mammals are fundamentally similar to those of amphibians and avians - i.e. anteroposterior positional information is acquired by mesoderm, mesoderm induces positional values within (neuro-) ectoderm and endoderm, and both events occur within a restricted window of time.

Neural crest formation in the head of the mouse embryo as observed using a new histological technique

Development ◽  
1981 ◽  
Vol 64 (1) ◽  
pp. 105-120
Author(s):  
David H. Nichols
Keyword(s):  
Epithelial Cells ◽  
Neural Crest ◽  
Mouse Embryo ◽  
Neural Plate ◽  
Differential Staining ◽  
Basal Surface ◽  
Surface Ectoderm ◽  
Histological Technique ◽  
Early Migration ◽  
Lateral Portion

A histological technique is described which results in the differential staining of neural crest cells. This is used to describe the formation and early migration of crest cells in the head of the mouse embryo. The first indications of crest formation are seen in the midbrain/anterior hindbrain at 3–4 somites where crest cells accumulate in the basal surface of the ectodermal epithelium near the future margin of the neural plate. Shortly thereafter (4–6 somites) these cells disrupt the basal surface of the epithelium and escape as mesenchyme. The apical epithelial cells in this region become the surface ectoderm adjacent to the neural plate. Subsequently, crest is formed from neural plate rather than surface ectoderm. In addition, mesenchyme is formed from presumptive surface ectoderm in a groove in the lateral portion of the fold between the forebrain and the midbrain. By 5–7 somites, crest mesenchyme is formed at all levels of the midbrain, hindbrain, and from the margins of the forebrain adjacent to the optic pits. Because of the bending of the embryonic axis, forebrain crest cells appear to migrate dorsally over the presumptive eye where they are met by ventrally migrating midbrain crest cells. Crest formation continues in the region of the midbrain and hindbrain during, and for an undetermined period after closure of the head folds at between 8 and 16 somites. These results demonstrate differences in the origin and timing of crest formation between chick and mouse. From this may be inferred different patterns of crest migration as well. In addition, the ability to directly observe early crest formation should aid in the analysis of the mechanisms by which epithelial cells are converted into mesenchyme.

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