Fgf8is required for pharyngeal arch and cardiovascular development in the mouse

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4613-4625 ◽  
Author(s):  
Radwan Abu-Issa ◽  
Graham Smyth ◽  
Ida Smoak ◽  
Ken-ichi Yamamura ◽  
Erik N. Meyers
Keyword(s):  
Craniofacial Development ◽  
Mouse Embryos ◽  
Pharyngeal Arch ◽  
Compound Heterozygous ◽  
Cardiovascular Development ◽  
Early Analysis ◽  
Pharyngeal Arches ◽  
The Face ◽  
Cardiovascular Defects ◽  
Additional Role

We present here an analysis of cardiovascular and pharyngeal arch development in mouse embryos hypomorphic for Fgf8. Previously, we have described the generation of Fgf8 compound heterozygous (Fgf8neo/–) embryos. Although early analysis demonstrated that some of these embryos have abnormal left-right (LR) axis specification and cardiac looping reversals, the number and type of cardiac defects present at term suggested an additional role for Fgf8 in cardiovascular development. Most Fgf8neo/– mutant embryos survive to term with abnormal cardiovascular patterning, including outflow tract, arch artery and intracardiac defects. In addition, these mutants have hypoplastic pharyngeal arches, small or absent thymus and abnormal craniofacial development. Neural crest cells (NCCs) populate the pharyngeal arches and contribute to many structures of the face, neck and cardiovascular system, suggesting that Fgf8 may be required for NCC development. Fgf8 is expressed within the developing pharyngeal arch ectoderm and endoderm during NCC migration through the arches. Analysis of NCC development in Fgf8neo/– mutant embryos demonstrates that NCCs are specified and migrate, but undergo cell death in areas both adjacent and distal to where Fgf8 is normally expressed. This study defines the cardiovascular defects present in Fgf8 mutants and supports a role for Fgf8 in development of all the pharyngeal arches and in NCC survival.

How frequent is the fifth arch artery?

2014 ◽  
Vol 25 (4) ◽  
pp. 628-646 ◽  
Author(s):  
Saurabh K. Gupta ◽  
Simon D. Bamforth ◽  
Robert H. Anderson
Keyword(s):  
World Literature ◽  
Pulmonary Atresia ◽  
Mouse Embryos ◽  
Pharyngeal Arch ◽  
Confounding Factors ◽  
Therapeutic Approaches ◽  
Pharyngeal Arches ◽  
The World ◽  
Pharyngeal Arch Arteries ◽  
Brachiocephalic Arteries

AbstractAlthough usually shown in embryology textbooks, the presence of the fifth pair of pharyngeal arch arteries has long been controversial. To the best of our knowledge, six pairs of bilaterally symmetrical arteries developing within the pharyngeal arches are yet to be found in any mammalian or avian species. Collateral channels between the distal ends of the fourth and sixth arch arteries, in contrast, have been found in up to half of all developing mouse embryos. In only one human embryo, again to the best of our knowledge, has a channel been found that extends from the aortic sac to the dorsal aorta, and hence qualifies as an arch artery. Despite these confounding factors in terms of the developmental heritage of the fifth arch arteries, the purported channels are invoked with increasing frequency to describe various lesions discovered in the setting of the congenitally malformed heart. Persistence of the artery of the fifth arch was initially proposed to explain double-barrelled aorta. It was subsequently proposed to account for various systemic-to-pulmonary channels feeding the pulmonary circulation in the setting of pulmonary atresia. It has also been claimed to persist so as to explain abnormal branching of the brachiocephalic arteries from the aortic arch. In the light of the ongoing doubts concerning the existence of the arteries of the fifth arch themselves, we have reviewed the various descriptions of purported fifth arch arteries within the world literature. We have then sought to validate the descriptions on the basis of our own understanding of development, for this purpose providing images of the remoulding arch arteries in the mouse so as to substantiate our conclusions. While accepting that our own interpretations are speculative, we suggest that more convincing alternative explanations can be advanced to account for the majority of lesions currently interpreted on the basis of persistence of the arteries of the fifth arches. Although the interpretations do not necessarily change the therapeutic approaches to the channels, appropriate description is important in terms of their classification.

scholarly journals Modulation of β-catenin levels is critical for cranial neural crest patterning and dispersal into first pharyngeal arch

2019 ◽  
Author(s):  
Alok Javali ◽  
Vairavan Laxmanan ◽  
Dasaradhi Palakodeti ◽  
Ramkumar Sambasivan
Keyword(s):  
Neural Crest ◽  
Neural Crest Cells ◽  
Mouse Embryos ◽  
Pharyngeal Arch ◽  
Cranial Neural Crest ◽  
Connective Tissues ◽  
Pharyngeal Arches ◽  
Cell Arrangement ◽  
Cranial Neural Crest Cells

AbstractVertebrate cranial neural crest cells (CNCC) are multipotent. Proximal to the source CNCC form the cranial ganglia. Distally, in the pharyngeal arches, they give rise to the craniofacial skeleton and connective tissues. Fate choices are made as CNCC pattern into distinct destination compartments. In spite of this importance, the mechanism patterning CNCC is poorly defined. Here, we report that a novel β-catenin-controlled switch in the cell arrangement is critical in patterning CNCC. In mouse embryos, at the first pharyngeal arch axial level, membrane β-catenin levels correlate with the extent of cell-cell adhesion and thus, with a collective or a dispersed state of CNCC. Using in vitro human neural crest model and chemical modulators of β-catenin levels, we show a requirement for down-modulating β-catenin for the collective-to-dispersed switch. Similarly, in β-catenin gain of function mutant mouse embryos, CNCC fail to disperse, which may underlie their failure to populate first pharyngeal arch. Thus, we show that β-catenin-mediated regulation of CNCC tissue architecture, a previously underappreciated mechanism, underlies the patterning of CNCC into fate-specific compartments.Summary statementThe report shows a crucial step in cranial neural crest patterning. Neural crest cells invading the pharyngeal arches transition from a collective to a dispersed state. This transition in cell arrangement is dependent on membrane β-catenin levels.

The development of the face, palate, and nose

2013 ◽  
Author(s):  
Martin E. Atkinson
Keyword(s):  
Oral Cavity ◽  
Nasal Cavity ◽  
Building Blocks ◽  
Pharyngeal Arch ◽  
Pharyngeal Arches ◽  
Mandibular Arch ◽  
The Face ◽  
Side Walls ◽  
Cavity Development ◽  
Arch Forms

In Chapter 21, we described the development of the pharyngeal arches and their derivatives. Craniofacial abnormalities account for about one third of all live birth defects. These arise during the development of the pharyngeal arches described in Chapter 21 or during the events described in this chapter. The first pharyngeal arch, the mandibular arch, is one of the basic building blocks needed to form the face and associated structures. The other major building block is the frontonasal process that covers the developing forebrain. The development of the face begins after the first pharyngeal arch forms around four weeks post-fertilization. At this stage, the head consists of a large bulge over the developing forebrain, approximating to the forehead and the mandibular arch in the position of the lower jaw. A slit between the frontonasal process and mandibular arch is continuous with the foregut tube; this slit is the primitive oral cavity or stomodeum. This primitive mouth cavity has no side walls where the cheeks would be and more significantly, there is no nasal cavity. Development of the nasal and oral cavities internally and the face externally proceeds at the same time over the course of the next eight weeks of development. Essentially, the nasal cavity is formed, then divided into two and separated from the oral cavity by the palate. The sequence of events is: • Development of the nasal cavity and first part of the palate, beginning the separation the oral and nasal cavities; • Development of the maxillary arch from the mandibular arch to form the cheeks and important structures contributing to the palate; • Completion of the components required to form the palate and separate the nasal cavity into right and left cavities; • Fusion of the building blocks to complete the separation of the nasal cavity and the separation of the nasal cavity from the oral cavity. As you can see in Figure 32.1A, the stomodeum is roofed by the frontonasal process and its floor is the fused mandibular arches.

scholarly journals Maternal iron deficiency perturbs embryonic cardiovascular development in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jacinta I. Kalisch-Smith ◽  
Nikita Ved ◽  
Dorota Szumska ◽  
Jacob Munro ◽  
Michael Troup ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Environment Interaction ◽  
Cardiovascular Development ◽  
Retinoic Acid Signalling ◽  
Gene Environment Interaction ◽  
Iron Administration ◽  
Gene Environment ◽  
Cardiovascular Defects ◽  
Craniofacial Defects ◽  
Maternal Iron

AbstractCongenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene–environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women.

scholarly journals Bichir external gills arise via heterochronic shift that accelerates hyoid arch development

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jan Stundl ◽  
Anna Pospisilova ◽  
David Jandzik ◽  
Peter Fabian ◽  
Barbora Dobiasova ◽  
...  
Keyword(s):  
Pharyngeal Arch ◽  
Developmental Sequence ◽  
Free Living ◽  
Pharyngeal Arches ◽  
Hyoid Arch ◽  
Early Appearance ◽  
Evolutionary Changes ◽  
Insight Into ◽  
Living Group ◽  
Early Larvae

In most vertebrates, pharyngeal arches form in a stereotypic anterior-to-posterior progression. To gain insight into the mechanisms underlying evolutionary changes in pharyngeal arch development, here we investigate embryos and larvae of bichirs. Bichirs represent the earliest diverged living group of ray-finned fishes, and possess intriguing traits otherwise typical for lobe-finned fishes such as ventral paired lungs and larval external gills. In bichir embryos, we find that the anteroposterior way of formation of cranial segments is modified by the unique acceleration of the entire hyoid arch segment, with earlier and orchestrated development of the endodermal, mesodermal, and neural crest tissues. This major heterochronic shift in the anteroposterior developmental sequence enables early appearance of the external gills that represent key breathing organs of bichir free-living embryos and early larvae. Bichirs thus stay as unique models for understanding developmental mechanisms facilitating increased breathing capacity.

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.

scholarly journals Cell - ECM Interactions Play Multiple Essential Roles in Aortic Arch Development

2020 ◽  
Author(s):  
Michael Warkala ◽  
Dongying Chen ◽  
AnnJosette Ramirez ◽  
Ali Jubran ◽  
Michael J Schonning ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Developmental Stages ◽  
Lineage Tracing ◽  
Confocal Imaging ◽  
Pharyngeal Arch ◽  
Cellular Mechanisms ◽  
Integrin Α5β1 ◽  
Pharyngeal Arches ◽  
Heart Field ◽  
Pharyngeal Arch Arteries

Rationale: Defects in the morphogenesis of the 4th pharyngeal arch arteries (PAAs) give rise to lethal birth defects. Understanding genes and mechanisms regulating PAA formation will provide important insights into the etiology and treatments for congenital heart disease. Objective: Cell-ECM interactions play essential roles in the morphogenesis of PAAs and their derivatives, the aortic arch artery (AAA) and its major branches; however, their specific functions are not well-understood. Previously, we demonstrated that integrin α5β1 and fibronectin (Fn1) expressed in the Isl1 lineages regulate PAA formation. The objective of the current studies was to investigate cellular mechanisms by which integrin α5β1 and Fn1 regulate AAA morphogenesis. Methods and Results: Using temporal lineage tracing, whole-mount confocal imaging, and quantitative analysis of the second heart field (SHF) and endothelial cell (EC) dynamics, we show that the majority of PAA EC progenitors arise by E7.5 in the SHF and contribute to pharyngeal arch endothelium between E7.5 and E9.5. Consequently, SHF-derived ECs in the pharyngeal arches form a uniform plexus of small blood vessels, which remodels into the PAAs by 35 somites. The remodeling of the vascular plexus is orchestrated by signals dependent on the pharyngeal ECM microenvironment, extrinsic to the endothelium. Conditional ablation of integrin α5β1 or Fn1 in the Isl1 lineages showed that signaling by the ECM regulates AAA morphogenesis at multiple steps: 1) accumulation of SHF-derived ECs in the pharyngeal arches, 2) remodeling of the uniform EC plexus in the 4th arches into the PAAs; and 3) differentiation of neural crest-derived cells adjacent to the PAA endothelium into vascular smooth muscle cells. Conclusions: PAA formation is a multi-step process entailing dynamic contribution of SHF-derived ECs to pharyngeal arches, the remodeling of endothelial plexus into the PAAs, and the remodeling of the PAAs into the AAA and its major branches. Cell-ECM interactions regulated by integrin α5β1 and Fn1 play essential roles at each of these developmental stages.

scholarly journals Tek (Tie2) is not required for cardiovascular development in zebrafish

Development ◽  
2020 ◽  
Vol 147 (19) ◽  
pp. dev193029 ◽  
Author(s):  
Zhen Jiang ◽  
Claudia Carlantoni ◽  
Srinivas Allanki ◽  
Ingo Ebersberger ◽  
Didier Y. R. Stainier
Keyword(s):  
Binding Site ◽  
Lymphatic Vessel ◽  
Vascular Malformations ◽  
Premature Termination Codon ◽  
Cardiovascular Development ◽  
Loss Of Function ◽  
Cardiovascular Defects ◽  
Vessel Development ◽  
Phylogenetic Profiling ◽  
Target Effects

ABSTRACTAngiopoietin/TIE signalling plays a major role in blood and lymphatic vessel development. In mouse, Tek (previously known as Tie2) mutants die prenatally due to a severely underdeveloped cardiovascular system. In contrast, in zebrafish, previous studies have reported that although embryos injected with tek morpholinos (MOs) exhibit severe vascular defects, tek mutants display no obvious vascular malformations. To further investigate the function of zebrafish Tek, we generated a panel of loss-of-function tek mutants, including RNA-less alleles, an allele lacking the MO-binding site, an in-frame deletion allele and a premature termination codon-containing allele. Our data show that all these mutants survive to adulthood with no obvious cardiovascular defects. MO injections into tek mutants lacking the MO-binding site or the entire tek locus cause similar vascular defects to those observed in MO-injected +/+ siblings, indicating off-target effects of the MOs. Surprisingly, comprehensive phylogenetic profiling and synteny analyses reveal that Tek was lost in the largest teleost clade, suggesting a lineage-specific shift in the function of TEK during vertebrate evolution. Altogether, these data show that Tek is dispensable for zebrafish development, and probably dispensable in most teleost species.

The Role of Retinoids in Normal and Abnormal Embryonic Craniofacial Morphogenesis

1992 ◽  
Vol 4 (1) ◽  
pp. 93-109 ◽  
Author(s):  
Joy M. Richman
Keyword(s):  
Craniofacial Development ◽  
Facial Growth ◽  
Specific Effects ◽  
The Face ◽  
Facial Development ◽  
Lines Of Evidence ◽  
Craniofacial Morphogenesis

The objective of this article is to evaluate the role of retinoids in the developing head and face. This article covers two lines of evidence that strongly support a role for retinoids in craniofacial development. First, the specific effects of exogenous retinoids on the head and face are covered and mechanisms for the specificity discussed. Second, the function of endogenous retinoids in facial development is discussed in relation to the distribution of retinoid-binding substances in the face. Finally, the interaction of retinoids with other genes known to be expressed in the face as well as other factors required for facial growth is discussed.

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