Trumpp, A., Depew, M. J., Rubenstein, J. L. R., Bishop, J. M. & Martin, G. R. Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes Dev. 13, 3136?3148

G.W. Hooper Foundation, Department of Microbiology, School of Medicine, University of California at San Francisco (UCSF), San Francisco, California 94143-0552, USA.
Genes & Development (Impact Factor: 10.8). 01/2000; 13(23):3136-48. DOI: 10.1101/gad.13.23.3136
Source: PubMed


In mammals, the first branchial arch (BA1) develops into a number of craniofacial skeletal elements including the jaws and teeth. Outgrowth and patterning of BA1 during early embryogenesis is thought to be controlled by signals from its covering ectoderm. Here we used Cre/loxP technology to inactivate the mouse Fgf8 gene in this ectoderm and have obtained genetic evidence that FGF8 has a dual function in BA1: it promotes mesenchymal cell survival and induces a developmental program required for BA1 morphogenesis. Newborn mutants lack most BA1-derived structures except those that develop from the distal-most region of BA1, including lower incisors. The data suggest that the BA1 primordium is specified into a large proximal region that is controlled by FGF8, and a small distal region that depends on other signaling molecules for its outgrowth and patterning. Because the mutant mice resemble humans with first arch syndromes that include agnathia, our results raise the possibility that some of these syndromes are caused by mutations that affect FGF8 signaling in BA1 ectoderm.

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Available from: Michael J Depew, Feb 05, 2014
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    • "Among those FGF ligands, FGF8 is known to be involved in the regulation of neural crest specification , acts as a chemoattractant for neural crest migration (Kubota and Ito, 2000; Monsoro-Burq et al., 2003, 2005; Sato et al., 2005), and functions as a pro-odontogenic factor (Chen et al., 1996; Neubüser et al., 1997; St Amand et al., 2000; Li et al., 2011). Fgf8 deficiency leads to severe developmental defects in multiple organs including dysmorphic mesencephalon and pharyngeal arches (Lee et al., 1997; Trumpp et al., 1999; Schneider et al., 2001; Abu-Issa et al., 2002; Trainor et al., 2002). In the present study, we investigated the role of FGF8 in CNC development by transgenic gain-of-function approach, complemented by in vitro cell culture studies. "
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    • "Notably, radial glia and their progeny (ependymal and neural progenitor cells) strongly express FGFR1 (Zheng et al. 2004; García-González et al. 2010; Gálvez- Contreras et al. 2012) and FGFR1 signalling regulates cilia length and function in diverse epithelia during development (Neugebauer et al. 2009). Moreover, FGFR1 is expressed in the motile cilia and FGF signalling is associated with tumour progression and several ciliopathies (Trumpp et al. 1999; Evans et al. 2002; Macatee et al. 2003; Creuzet et al. 2004; Szabo-Rogers et al. 2008; Zaghloul and Brugmann 2011). Hence, FGFR1 expression in ependymal cells may actually be important for ependymal ciliary beating in the lateral ventricles. "
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    • "Fgf8 hypomorphic murine mutants (Fgf8 D/neo in Fig. 4d) exhibit asymmetric development of the nasal capsules as well as DA in the development of the neurocranial base and optic capsules (Fig. 4d; Griffin et al., 2013). Tissue-specific deletion of Fgf8 in the mouse oral ectoderm , moreover, results in a significant loss of jaw elements (Trumpp et al., 1999). Notably, asymmetry of the jaw is often seen in these mutants, and the left side appears to be more severely affected. "
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