Trumpp A, Depew MJ, Rubenstein JL, Bishop JM, Martin GR.. 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

ABSTRACT 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.

Download full-text


Available from: Michael J Depew, Feb 05, 2014
56 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: New subventricular zone (SVZ)-derived neuroblasts that migrate via the rostral migratory stream are continuously added to the olfactory bulb (OB) of the adult rodent brain. Anosmin-1 (A1) is an extracellular matrix protein that binds to FGF receptor 1 (FGFR1) to exert its biological effects. When mutated as in Kallmann syndrome patients, A1 is associated with severe OB morphogenesis defects leading to anosmia and hypogonadotropic hypogonadism. Here, we show that A1 over-expression in adult mice strongly increases proliferation in the SVZ, mainly with symmetrical divisions, and produces substantial morphological changes in the normal SVZ architecture, where we also report the presence of FGFR1 in almost all SVZ cells. Interestingly, for the first time we show FGFR1 expression in the basal body of primary cilia in neural progenitor cells. Additionally, we have found that A1 over-expression also enhances neuroblast motility, mainly through FGFR1 activity. Together, these changes lead to a selective increase in several GABAergic interneuron populations in different OB layers. These specific alterations in the OB would be sufficient to disrupt the normal processing of sensory information and consequently alter olfactory memory. In summary, this work shows that FGFR1-mediated A1 activity plays a crucial role in the continuous remodelling of the adult OB.
    Brain Structure and Function 10/2014; DOI:10.1007/s00429-014-0904-8 · 5.62 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Much of the gnathostome (jawed vertebrate) evolutionary radiation was dependent upon the ability to sense and interpret the environment and subsequently act upon this information through utilization of a specialized mode of feeding involving the jaws. While the gnathostome skull, reflective of the vertebrate baüplan, typically is bilaterally symmetric with right (dextral) and left (sinistral) halves essentially representing mirror images along the midline, both adaptive and abnormal asymmetries have appeared. Herein we provide a basic primer on studies of the asymmetric development of the gnathostome skull, touching briefly on asymmetry as a field of study, then describing the nature of cranial development and finally underscoring evolutionary and functional aspects of left-right asymmetric cephalic development. © 2014 Wiley Periodicals, Inc.
    genesis 06/2014; 52(6). DOI:10.1002/dvg.22786 · 2.02 Impact Factor
  • Source
    • "s have specifically lost transcriptionally unique intermedi - ate or distal domains . That hypothesis may be supported by evidence from transcrip - tion factors regulated through other signaling pathways in the arches . Pitx1 expression and Msx1 expression have been described to be unaltered by loss of Fgf8 from the ectoderm ( Liu et al . , 2005 ; Trumpp et al . , 1999 ) . Interestingly , the pattern of Msx1 expression is similar to Lhx7 , as is the pattern change in Foxi3 mutants , with two BA1 Msx1 domains in the wild type embryo reduced to one domain in the Foxi3 mutant . Although the major morphological differences between Foxi3 mutants and wild type embryos result in a noticeable decrease in Pitx"
    [Show abstract] [Hide abstract]
    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.
    Developmental Biology 06/2014; 390(1). DOI:10.1016/j.ydbio.2014.03.004 · 3.55 Impact Factor
Show more