Homeotic transformation of branchial arch identity after Hoxa2 overexpression

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5355-5365 ◽  
Author(s):  
G.A. Grammatopoulos ◽  
E. Bell ◽  
L. Toole ◽  
A. Lumsden ◽  
A.S. Tucker
Keyword(s):  
Neural Crest ◽  
Branchial Arch ◽  
Reverse Transformation ◽  
Surrounding Tissue ◽  
Homeotic Transformation ◽  
Branchial Arches ◽  
Arch Neural

Overexpression of Hoxa2 in the chick first branchial arch leads to a transformation of first arch cartilages, such as Meckel's and the quadrate, into second arch elements, such as the tongue skeleton. These duplicated elements are fused to the original in a similar manner to that seen in the Hoxa2 knockout, where the reverse transformation of second to first arch morphology is observed. This confirms the role of Hoxa2 as a selector gene specifying second arch fate. When first arch neural crest alone is targeted, first arch elements are lost, but the Hoxa2-expressing crest is unable to develop into second arch elements. This is not due to Hoxa2 preventing differentiation of cartilages. Upregulation of a second arch marker in the first arch, and homeotic transformation of cartilage elements is only produced after global Hoxa2 overexpression in the crest and the surrounding tissue. Thus, although the neural crest appears to contain some patterning information, it needs to read cues from the environment to form a coordinated pattern. Hoxa2 appears to exert its effect during differentiation of the cartilage elements in the branchial arches, rather than during crest migration, implying that pattern is determined quite late in development.

Role of the neural crest in development of the trabeculae and branchial arches in embryonic sea lamprey, Petromyzon marinus (L)

Development ◽  
1988 ◽  
Vol 102 (2) ◽  
pp. 301-310 ◽  
Author(s):  
R.M. Langille ◽  
B.K. Hall
Keyword(s):  
Neural Crest ◽  
Skeletal Development ◽  
Petromyzon Marinus ◽  
Branchial Arches ◽  
Artificial Fertilization ◽  
Vertebrate Skeleton ◽  
The Brain ◽  
Head Skeleton ◽  
Neurula Stage

Lamprey embryos were obtained by artificial fertilization to ascertain the contributions made by the neural crest to the head skeleton. Early-neurula-stage embryos of Petromyzon marinus were subjected to neural crest extirpation along the anterior half from one of seven zones, raised to a larval stage at which control larvae exhibit well-developed skeletons and analysed by light microscopy for any abnormalities to the cranial and visceral skeleton. The removal of premigratory neural crest at the level of the anterior prosencephalon (zone I) and at the level of somites 6 to 8 (zone VII) had no effect on skeletal development. However, the extirpation of neural crest from the intervening regions was positively correlated with deletions/reductions to the trabeculae (basicranial elements) and to the branchial arches (viscerocranial elements). Alterations to the trabeculae (16/27 cases, or 59%) occurred only after extirpation of zones II-V (corresponding to the posterior prosencephalon to midrhombencephalon) while alterations to the branchial arches (21/28 cases, or 75%) occurred only after removal of neural crest from zones III-VI (corresponding to the mesencephalon to the level of the fifth somite). Furthermore, the first three branchial arches were correlated in a majority of cases with neural crest from zone III, the next two arches with zones IV, V and VI and the last two arches with zone VI. Organs that develop within or adjacent to the area of neural crest extirpation such as the brain, notochord and lateral mesodermal derivatives were not affected. Parachordals were never altered by the operations nor were there any discernible changes to developing mucocartilage or to the prechondrogenic otic capsule. The contributions of the neural crest to the petromyzonid head skeleton described herein are compared with the roles of neural crest in the development of cranial and visceral skeletal elements in other vertebrates. The importance of these findings to the current hypothesis of the phylogeny of the vertebrate skeleton and the central role of the neural crest in vertebrate cephalization is discussed.

Jaw and branchial arch mutants in zebrafish I: branchial arches

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 329-344 ◽  
Author(s):  
T.F. Schilling ◽  
T. Piotrowski ◽  
H. Grandel ◽  
M. Brand ◽  
C.P. Heisenberg ◽  
...  
Keyword(s):  
Neural Crest ◽  
Zebrafish Embryo ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Pigment Cells ◽  
Pharyngeal Arches ◽  
Pectoral Fins ◽  
Branchial Arches ◽  
Group Members ◽  
The Brain

Jaws and branchial arches together are a basic, segmented feature of the vertebrate head. Seven arches develop in the zebrafish embryo (Danio rerio), derived largely from neural crest cells that form the cartilaginous skeleton. In this and the following paper we describe the phenotypes of 109 arch mutants, focusing here on three classes that affect the posterior pharyngeal arches, including the hyoid and five gill-bearing arches. In lockjaw, the hyoid arch is strongly reduced and subsets of branchial arches do not develop. Mutants of a large second class, designated the flathead group, lack several adjacent branchial arches and their associated cartilages. Five alleles at the flathead locus all lead to larvae that lack arches 4–6. Among 34 other flathead group members complementation tests are incomplete, but at least six unique phenotypes can be distinguished. These all delete continuous stretches of adjacent branchial arches and unpaired cartilages in the ventral midline. Many show cell death in the midbrain, from which some neural crest precursors of the arches originate. lockjaw and a few mutants in the flathead group, including pistachio, affect both jaw cartilage and pigmentation, reflecting essential functions of these genes in at least two neural crest lineages. Mutants of a third class, including boxer, dackel and pincher, affect pectoral fins and axonal trajectories in the brain, as well as the arches. Their skeletal phenotypes suggest that they disrupt cartilage morphogenesis in all arches. Our results suggest that there are sets of genes that: (1) specify neural crest cells in groups of adjacent head segments, and (2) function in common genetic pathways in a variety of tissues including the brain, pectoral fins and pigment cells as well as pharyngeal arches.

Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4811-4818 ◽  
Author(s):  
B.L. Thomas ◽  
A.S. Tucker ◽  
M. Qui ◽  
C.A. Ferguson ◽  
Z. Hardcastle ◽  
...  
Keyword(s):  
Neural Crest ◽  
Homeobox Gene ◽  
Branchial Arch ◽  
Cranial Neural Crest ◽  
Loss Of Function ◽  
Molecular Events ◽  
Maxillary Molar ◽  
Molar Teeth ◽  
Cranial Neural Crest Cells ◽  
Arch Neural

The molecular events of odontogenic induction are beginning to be elucidated, but until now nothing was known about the molecular basis of the patterning of the dentition. A role for Dlx-1 and Dlx-2 genes in patterning of the dentition has been proposed with the genes envisaged as participating in an ‘odontogenic homeobox gene code’ by specifying molar development. This proposal was based on the restricted expression of the genes in molar ectomesenchyme derived from cranial neural crest cells prior to tooth initiation. Mice with targeted null mutations of both Dlx-1 and Dlx-2 homeobox genes do not develop maxillary molar teeth but incisors and mandibular molars are normal. We have carried out heterologous recombinations between mutant and wild-type maxillary epithelium and mesenchyme and show that the ectomesenchyme underlying the maxillary molar epithelium has lost its odontogenic potential. Using molecular markers of branchial arch neural crest (Barx1) and commitment to chondrogenic differentiation (Sox9), we show that this population alters its fate from odontogenic to become chondrogenic. These results provide evidence that a subpopulation of cranial neural crest is specified as odontogenic by Dlx-1 and Dlx-2 genes. Loss of function of these genes results in reprogramming of this population of ectomesenchyme cells into chondrocytes. This is the first indication that the development of different shaped teeth at different positions in the jaws is determined by independent genetic pathways.

scholarly journals Transcriptome profiling of the branchial arches reveals cell type composition and a conserved signature of neural crest cell invasion

2020 ◽  
Author(s):  
Jason A Morrison ◽  
Rebecca McLennan ◽  
Jessica M Teddy ◽  
Allison R Scott ◽  
Jennifer C Kasemeier-Kulesa ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Invasion ◽  
Neural Crest Cell ◽  
Branchial Arch ◽  
Tissue Growth ◽  
Cell Populations ◽  
Label Free ◽  
Cell Type ◽  
Mesoderm Cell ◽  
Branchial Arches

ABSTRACTThe vertebrate branchial arches that give rise to structures of the head, neck, and heart form with very dynamic tissue growth and well-choreographed neural crest, ectoderm, and mesoderm cell dynamics. Although this morphogenesis has been studied by marker expression and fate-mapping, the mechanisms that control the collective migration and diversity of the neural crest and surrounding tissues remain unclear, in part due to the effects of averaging and need for cell isolation in conventional transcriptome analysis experiments of multiple cell populations. We used label free single cell RNA sequencing on 95,000 individual cells at 2 developmental stages encompassing formation of the first four chick branchial arches to measure the transcriptional states that define the cellular hierarchy and invasion signature of the migrating neural crest. The results confirmed basic features of cell type diversity and led to the discovery of many novel markers that discriminate between axial level and distal-to-proximal cell populations within the branchial arches and neural crest streams. We identified the transcriptional signature of the most invasive neural crest that is conserved within each branchial arch stream and elucidated a set of genes common to other cell invasion signatures in types in cancer, wound healing and development. These data robustly delineate molecularly distinct cell types within the branchial arches and identify important molecular transitions within the migrating neural crest during development.

A signaling cascade involving endothelin-1, dHAND and msx1 regulates development of neural-crest-derived branchial arch mesenchyme

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3005-3014 ◽  
Author(s):  
T. Thomas ◽  
H. Kurihara ◽  
H. Yamagishi ◽  
Y. Kurihara ◽  
Y. Yazaki ◽  
...  
Keyword(s):  
Neural Crest ◽  
Regulatory Elements ◽  
Branchial Arch ◽  
Limb Bud ◽  
Abnormal Development ◽  
Cardiac Defects ◽  
Endothelin 1 ◽  
The Third ◽  
Branchial Arches ◽  
Catch 22

Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived branchial arches and branchial arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the branchial arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the branchial arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the branchial and aortic arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second arches are hypoplastic secondary to programmed cell death and the third and fourth arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the branchial arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null branchial arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal branchial arch. Complete disruption of this molecular pathway results in growth failure of the branchial arches from apoptosis, while partial disruption leads to defects of branchial arch derivatives, similar to those seen in CATCH-22 syndrome.

scholarly journals Rhombomere rotation reveals that multiple mechanisms contribute to the segmental pattern of hindbrain neural crest migration

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 1777-1790 ◽  
Author(s):  
J. Sechrist ◽  
T. Scherson ◽  
M. Bronner-Fraser
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Otic Vesicle ◽  
Branchial Arches ◽  
Migratory Pattern ◽  
Neural Crest Migration ◽  
Surgical Manipulation ◽  
Otic Vesicles

Hindbrain neural crest cells adjacent to rhombomeres 2 (r2), r4 and r6 migrate in a segmental pattern, toward the first, second and third branchial arches, respectively. Although all rhombomeres generate neural crest cells, those arising from r3 and r5 deviate rostrally and caudally (J. Sechrist, G. Serbedzija, T. Scherson, S. Fraser and M. Bronner-Fraser (1993) Development 118, 691–703). We have altered the rostrocaudal positions of the cranial neural tube, adjacent ectoderm/mesoderm or presumptive otic vesicle to examine tissue influences on this segmental migratory pattern. After neural tube rotation, labeled neural crest cells follow pathways generally appropriate for their new position after grafting. For example, when r3 and r4 were transposed, labeled r3 cells migrated laterally to the second branchial arch whereas labeled r4 cells primarily deviated caudally toward the second arch, with some cells moving rostrally toward the first. In contrast to r4 neural crest cells, transposed r3 cells leave the neural tube surface in a polarized manner, near the r3/4 border. Surprisingly, some labeled neural crest cells moved directionally toward small ectopic otic vesicles that often formed in the ectoderm adjacent to grafted r4. Similarly, they moved toward grafted or displaced otic vesicles. In contrast, surgical manipulation of the mesoderm adjacent to r3 and r4 had no apparent effects. Our results offer evidence that neural crest cells migrate directionally toward the otic vesicle, either by selective attraction or pathway-derived cues.

BMP signaling is essential for development of skeletogenic and neurogenic cranial neural crest

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 1095-1104 ◽  
Author(s):  
B. Kanzler ◽  
R.K. Foreman ◽  
P.A. Labosky ◽  
M. Mallo
Keyword(s):  
Transgenic Mice ◽  
Neural Crest ◽  
Essential Role ◽  
Expression Patterns ◽  
Neural Crest Cells ◽  
Bmp Signaling ◽  
Cranial Neural Crest ◽  
Temporal Expression ◽  
Branchial Arches

BMP signaling is essential for a wide variety of developmental processes. To evaluate the role of Bmp2/4 in cranial neural crest (CNC) formation or differentiation after its migration into the branchial arches, we used Xnoggin to block their activities in specific areas of the CNC in transgenic mice. This resulted in depletion of CNC cells from the targeted areas. As a consequence, the branchial arches normally populated by the affected neural crest cells were hypomorphic and their skeletal and neural derivatives failed to develop. In further analyses, we have identified Bmp2 as the factor required for production of migratory cranial neural crest. Its spatial and temporal expression patterns mirror CNC emergence and Bmp2 mutant embryos lack both branchial arches and detectable migratory CNC cells. Our results provide functional evidence for an essential role of BMP signaling in CNC development.

Ectopic expression of Hoxa-1 in the zebrafish alters the fate of the mandibular arch neural crest and phenocopies a retinoic acid-induced phenotype

Development ◽  
1996 ◽  
Vol 122 (3) ◽  
pp. 735-746 ◽  
Author(s):  
D. Alexandre ◽  
J.D. Clarke ◽  
E. Oxtoby ◽  
Y.L. Yan ◽  
T. Jowett ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Ectopic Expression ◽  
Head Region ◽  
Hox Gene ◽  
Abnormal Growth ◽  
Primary Body ◽  
Arch Neural ◽  
The Relationship

Considerable evidence has demonstrated that retinoic acid influences the formation of the primary body axis in vertebrates and that this may occur through the regulation of Hox gene expression. In this study, we show that the phenotype induced by exogenous retinoic acid in the zebrafish can also be generated by the overexpression of Hoxa-1 following injection of synthetic RNA into the fertilised egg. The isolation, sequence and expression pattern of the zebrafish Hoxa-1 gene is described. We show that exogenously applied retinoic acid causes the ectopic accumulation of Hoxa-1 message during gastrulation in the hypoblast in the head region. Overexpression of Hoxa-1 following injection of RNA causes abnormal growth of the anterior hindbrain, duplication of Mauthner neurons in rhombomere (r) 2 and fate changes of r2 mesenchymal and neurogenic neural crest. These results are discussed in terms of the role of Hoxa-1 in controlling anterior hindbrain patterning and the relationship between expression of Hoxa-1 and retinoic acid.

scholarly journals Pharmacological inactivation of the endothelin type A receptor in the early chick embryo: a model of mispatterning of the branchial arch derivatives

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 4931-4941 ◽  
Author(s):  
H. Kempf ◽  
C. Linares ◽  
P. Corvol ◽  
J.M. Gasc
Keyword(s):  
Chick Embryo ◽  
Neural Crest ◽  
Type A ◽  
Branchial Arch ◽  
In Ovo ◽  
Time Of Application ◽  
Branchial Arches ◽  
Eta Receptor ◽  
Temporal Expression Pattern ◽  
High Level

In the present study, we have applied an antagonist treatment to the chick embryo in ovo in order to demonstrate and dissect the essential roles of the endothelin type A (ETA) receptor in the embryonic development. We have cloned, sequenced and expressed the cDNA of the chick ETA receptor and shown that its affinity for endothelin antagonists is very similar to that shown by its mammalian counterparts. We have studied the spatio-temporal expression pattern of this receptor by in situ hybridization and shown that there is a high level of its mRNA within the mesenchyme of the branchial arches at E3-E5, in keeping with the direct effect of endothelin-1 (ET-1) on the fate of this region of the embryo. Unlike the endothelin type B (ETB) receptor mRNA, ETA mRNA is not expressed in neural crest cells during emigration from the neural tube, but is detected in neural crest-derived ectomesenchyme of the branchial arches. Finally, the functional involvement of this receptor in craniofacial and cardiovascular organogenesis was assessed by selectively inactivating the ETA receptor with specific antagonists applied during the time period corresponding to the expression of the ETA receptor and colonisation of the branchial arches. Embryos treated by these antagonists show a severe reduction and dysmorphogenesis of the hypobranchial skeleton, as well as heart and aortic arch derivative defects. This phenotype is very similar to that obtained in mice by gene inactivations of ET-1 and ETA. These results are observed with ETA antagonists but not with an ETB antagonist, and are dependent on the dose of the antagonists used and on the time of application to the embryo. Altogether, these data strongly show that the ET-1/ETA pathway, in chicken as in mammals, is a major factor involved directly and functionally in morphogenesis of the face and heart. This experimental model of pharmacological inactivation of a gene product described in this study offers a simple and rapid alternative to gene inactivation in mouse. This strategy can be applied to other ligand-receptor systems and extended to compounds of various chemical and functional natures.

scholarly journals Analysis of cranial neural crest migratory pathways in axolotl using cell markers and transplantation

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2751-2761 ◽  
Author(s):  
H. Epperlein ◽  
D. Meulemans ◽  
M. Bronner-Fraser ◽  
H. Steinbeisser ◽  
M.A. Selleck
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Cranial Neural Crest ◽  
Branchial Arches ◽  
Trunk Neural Crest ◽  
Cranial Neural Crest Cells ◽  
Random Nature

We have examined the ability of normal and heterotopically transplanted neural crest cells to migrate along cranial neural crest pathways in the axolotl using focal DiI injections and in situ hybridization with the neural crest marker, AP-2. DiI labeling demonstrates that cranial neural crest cells migrate as distinct streams along prescribed pathways to populate the maxillary and mandibular processes of the first branchial arch, the hyoid arch and gill arches 1–4, following migratory pathways similar to those observed in other vertebrates. Another neural crest marker, the transcription factor AP-2, is expressed by premigratory neural crest cells within the neural folds and migrating neural crest cells en route to and within the branchial arches. Rotations of the cranial neural folds suggest that premigratory neural crest cells are not committed to a specific branchial arch fate, but can compensate when displaced short distances from their targets by migrating to a new target arch. In contrast, when cells are displaced far from their original location, they appear unable to respond appropriately to their new milieu such that they fail to migrate or appear to migrate randomly. When trunk neural folds are grafted heterotopically into the head, trunk neural crest cells migrate in a highly disorganized fashion and fail to follow normal cranial neural crest pathways. Importantly, we find incorporation of some trunk cells into branchial arch cartilage despite the random nature of their migration. This is the first demonstration that trunk neural crest cells can form cartilage when transplanted to the head. Our results indicate that, although cranial and trunk neural crest cells have inherent differences in ability to recognize migratory pathways, trunk neural crest can differentiate into cranial cartilage when given proper instructive cues.

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