An essential role for Fgfs in endodermal pouch formation influences later craniofacial skeletal patterning
Institute of Neuroscience, 1254 University of Oregon, Eugene, OR 97403-1254, USA. Development
(Impact Factor: 6.46).
12/2004; 131(22):5703-16. DOI: 10.1242/dev.01444
Fibroblast growth factor (Fgf) proteins are important regulators of pharyngeal arch development. Analyses of Fgf8 function in chick and mouse and Fgf3 function in zebrafish have demonstrated a role for Fgfs in the differentiation and survival of postmigratory neural crest cells (NCC) that give rise to the pharyngeal skeleton. Here we describe, in zebrafish, an earlier, essential function for Fgf8 and Fgf3 in regulating the segmentation of the pharyngeal endoderm into pouches. Using time-lapse microscopy, we show that pharyngeal pouches form by the directed lateral migration of discrete clusters of endodermal cells. In animals doubly reduced for Fgf8 and Fgf3, the migration of pharyngeal endodermal cells is disorganized and pouches fail to form. Transplantation and pharmacological experiments show that Fgf8 and Fgf3 are required in the neural keel and cranial mesoderm during early somite stages to promote first pouch formation. In addition, we show that animals doubly reduced for Fgf8 and Fgf3 have severe reductions in hyoid cartilages and the more posterior branchial cartilages. By examining early pouch and later cartilage phenotypes in individual animals hypomorphic for Fgf function, we find that alterations in pouch structure correlate with later cartilage defects. We present a model in which Fgf signaling in the mesoderm and segmented hindbrain organizes the segmentation of the pharyngeal endoderm into pouches. Moreover, we argue that the Fgf-dependent morphogenesis of the pharyngeal endoderm into pouches is critical for the later patterning of pharyngeal cartilages.
Available from: dev.biologists.org
- "As the pouch defects of tbx1 mutants are reminiscent of those seen upon inhibition of Wnt (Choe et al., 2013) or Fgf (Crump et al., 2004a) signaling, we explored whether the expression of individual Wnt and Fgf ligands might require Tbx1 function. In particular, fgf8a and wnt11r are expressed in the mesoderm during pouch initiation (Choe et al., 2013; Nechiporuk et al., 2007; Reifers et al., 2000), and we have previously reported requirements for both these genes in pouch morphogenesis (Choe et al., 2013; Crump et al., 2004a). In wild type, we observed expression of fgf8a and wnt11r in distinct subsets of the nkx2.5:GFP-positive "
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ABSTRACT: The pharyngeal pouches are a segmental series of epithelial structures that organize the embryonic vertebrate face. In mice and zebrafish that carry mutations in homologs of the DiGeorge syndrome gene TBX1, a lack of pouches correlates with severe craniofacial defects, yet how Tbx1 controls pouch development remains unclear. Using mutant and transgenic rescue experiments in zebrafish, we show that Tbx1 functions in the mesoderm to promote the morphogenesis of pouch-forming endoderm through wnt11r and fgf8a expression. Consistently, compound losses of wnt11r and fgf8a phenocopy tbx1 mutant pouch defects, and mesoderm-specific restoration of Wnt11r and Fgf8a rescues tbx1 mutant pouches. Time-lapse imaging further reveals that Fgf8a acts as a Wnt11r-dependent guidance cue for migrating pouch cells. We therefore propose a two-step model in which Tbx1 coordinates the Wnt-dependent epithelial destabilization of pouch-forming cells with their collective migration towards Fgf8a-expressing mesodermal guideposts.
Available from: Thomas Butts
- "The formation of the pharyngeal pouches requires signals from the surrounding mesodermal and neural tissues and it has been shown that Fgf function is necessary for the formation of all of the pouches . There are, however, also significant differences between the development of the anterior and posterior pouches. "
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ABSTRACT: Segmentation is a feature of the body plans of a number of diverse animal groupings, including the annelids, arthropods and chordates. However, it has been unclear whether or not these different manifestations of segmentation are independently derived or have a common origin. Central to this issue is whether or not there are common developmental mechanisms that establish segmentation and the evolutionary origins of these processes. A fruitful way to address this issue is to consider how segmentation in vertebrates is directed. During vertebrate development three different segmental systems are established: the somites, the rhombomeres and the pharyngeal arches. In each an iteration of parts along the long axis is established. However, it is clear that the formation of the somites, rhombomeres or pharyngeal arches have little in common, and as such there is no single segmentation process. These different segmental systems also have distinct evolutionary histories, thus highlighting the fact that segmentation can and does evolve independently at multiple points. We conclude that the term segmentation indicates nothing more than a morphological description and that it implies no mechanistic similarity. Thus it is probable that segmentation has arisen repeatedly during animal evolution.
Available from: sciencedirect.com
- "9 along the entire extent of pharyngeal endoderm at both ages in Foxi3 mutants , whereas Pax9 is restricted to pouches in wild type embryos . support cranial neural crest cell survival and branchial arch devel - opment is conserved from fish to mammals , and loss of pharyngeal Fgfs leads to missing craniofacial skeletal structures in vertebrates ( Crump et al . , 2004 ; Trumpp et al . , 1999 ) . Foxi3 and Fgf8 are expressed in similar patterns in the pharyngeal region , and Foxi3 mutants and Fgf8 branchial ectoderm - conditional knockouts have similar phenotypes , in particular , a significantly reduced mandible and concomitant apoptosis of cranial neural crest cells in the first arch ( Abu - Issa et"
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ABSTRACT: The bones of the vertebrate face develop from transient embryonic branchial arches that are populated by cranial neural crest cells. We have characterized a mouse mutant for the Forkhead family transcription factor Foxi3, which is expressed in branchial ectoderm and endoderm. Foxi3 mutant mice are not viable and display severe branchial arch-derived facial skeleton defects, including absence of all but the most distal tip of the mandible and complete absence of the inner, middle and external ear structures. Although cranial neural crest cells of Foxi3 mutants are able to migrate, populate the branchial arches and display some elements of correct proximo-distal patterning, they succumb to apoptosis from embryonic day 9.75 onwards. We show this cell death correlates with a delay in expression of Fgf8 in branchial arch ectoderm and a failure of neural crest cells in the arches to express FGF-responsive genes. Zebrafish foxi1 is also expressed in branchial arch ectoderm and endoderm, and morpholino knockdown of foxi1 also causes apoptosis of neural crest in the branchial arches. We show that heat shock induction of fgf3 in zebrafish arch tissue can rescue cell death in foxi1 morphants. Our results suggest that Foxi3 may play a role in the establishment of signaling centers in the branchial arches that are required for neural crest survival, patterning and the subsequent development of branchial arch derivatives.
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