Control of retinoic acid synthesis and FGF expression in the nasal pit is required to pattern the craniofacial skeleton

Abstract

Endogenous retinoids are important for patterning many aspects of the embryo including the branchial arches and frontonasal region of the embryonic face. The nasal placodes express retinaldehyde dehydrogenase-3 (RALDH3) and thus retinoids from the placode are a potential patterning influence on the developing face. We have carried out experiments that have used Citral, a RALDH antagonist, to address the function of retinoid signaling from the nasal pit in a whole embryo model. When Citral-soaked beads were implanted into the nasal pit of stage 20 chicken embryos, the result was a specific loss of derivatives from the lateral nasal prominences. Providing exogenous retinoic acid residue development of the beak demonstrating that most Citral-induced defects were produced by the specific blocking of RA synthesis. The mechanism of Citral effects was a specific increase in programmed cell death on the lateral (lateral nasal prominence) but not the medial side (frontonasal mass) of the nasal pit. Gene expression studies were focused on the Bone Morphogenetic Protein (BMP) pathway, which has a well-established role in programmed cell death. Unexpectedly, blocking RA synthesis decreased rather than increased Msx1, Msx2, and Bmp4 expression. We also examined cell survival genes, the most relevant of which was Fgf8, which is expressed around the nasal pit and in the frontonasal mass. We found that Fgf8 was not initially expressed along the lateral side of the nasal pit at the start of our experiments, whereas it was expressed on the medial side. Citral prevented upregulation of Fgf8 along the lateral edge and this may have contributed to the specific increase in programmed cell death in the lateral nasal prominence. Consistent with this idea, exogenous FGF8 was able to prevent cell death, rescue most of the morphological defects and was able to prevent a decrease in retinoic acid receptorbeta (Rarbeta) expression caused by Citral. Together, our results demonstrate that endogenous retinoids act upstream of FGF8 and the balance of these two factors is critical for regulating programmed cell death and morphogenesis in the face. In addition, our data suggest a novel role for endogenous retinoids from the nasal pit in controlling the precise downregulation of FGF in the center of the frontonasal mass observed during normal vertebrate development.

The function and regulation of TBX22 in avian frontonasal morphogenesis

“…We base this conclusion in part because there are no temporally regulated increases in apoptosis following the downregulation of FGF8 and TBX22 at stage 22 (McGonnell et al, 1998;Ashique et al, 2002a;Song et al, 2004). We could not detect a decrease in apoptosis in viral injected embryos.…”

21st Century neontology and the comparative development of the vertebrate skull

“…Examination of the expression patterns of genes involved in the signaling cascades of Bmp, Fgf, RA, and Shh, as well as the loss-and gain-offunction experimental manipulations of these molecules in chicks, generally support their homologous roles (at least at a gross level), suggesting some level of conservation between birds and mammals in their elaboration of jaw development (e.g., Bally-Cuif et al, 1995;Wall and Hogan, 1995;Barlow and Francis-West, 1997;Helms et al, 1997;Hu and Helms, 1999;Sun et al, 2000;Lee et al, 2001;Schneider et al, 2001;Ashique et al, 2002;Mina et al, 2002;Hu et al, 2003;Schneider and Helms, 2003;Song et al, 2004;Tucker and Lumsden, 2004;Wu et al, 2004;Marcucio et al, 2005;Havens et al, 2005). The information gleaned from the many studies of the application or repression of signaling cascades in the facial primordial of chicks highlight an important point regarding the hinge and caps model and jaw development: such studies collectively emphasize the synergy and juxtaposition of combinations of these signaling molecules-in particular in the caps regions and pharyngeal plate-in how such molecules regulate jaw development.…”

Foxg1Is Required for Development of the Vertebrate Olfactory System

“…A study in the chick suggests that Fgf8 expressed in the anterior neural ridge specifies olfactory tissue expressing Foxg1 (Bailey et al, 2006). It is unclear whether neighboring non-neural ectoderm secreting Fgf8 at the olfactory placode stage continues to specify new placodal cells later in development (Kawauchi et al, 2005), or whether all existing Foxg1-positive cells are specified at the neural plate stage and instead rely on Fgf8 for survival in the olfactory placode (Song et al, 2004). Whatever the case, from the present data, we propose that Foxg1 is required to establish a population of proliferating progenitor cells in the invaginating olfactory pit.…”