Control of retinoic acid synthesis and FGF expression in the nasal pit is required to pattern the craniofacial skeleton
| Autor: | J.N. Hui, Y. Song, Joy M. Richman, Kathy Fu |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Embryo
Nonmammalian Receptors Retinoic Acid Retinoic acid Bone Morphogenetic Protein 4 Chick Embryo FGF8 Craniofacial Abnormalities chemistry.chemical_compound Citral 0302 clinical medicine Morphogenesis Lateral nasal prominence Retinoid In Situ Hybridization 0303 health sciences Cell Death Gene Expression Regulation Developmental Nasal pit Retinaldehyde dehydrogenase Cell biology medicine.anatomical_structure Bone morphogenetic protein 4 Bone Morphogenetic Proteins embryonic structures Signal Transduction medicine.drug medicine.medical_specialty animal structures Fibroblast Growth Factor 8 medicine.drug_class Acyclic Monoterpenes Embryonic Structures Tretinoin Nose Biology Bone morphogenetic protein Bone and Bones 03 medical and health sciences Internal medicine In Situ Nick-End Labeling medicine Animals Molecular Biology Skeleton Body Patterning 030304 developmental biology Rarβ Homeodomain Proteins MSX1 Transcription Factor Retinoid synthesis Chicken embryo Cell Biology Embryo Mammalian Fibroblast Growth Factors Endocrinology chemistry Face Monoterpenes 030217 neurology & neurosurgery Transcription Factors Developmental Biology |
| Zdroj: | Developmental Biology. 276:313-329 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2004.08.035 |
| Popis: | 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 receptorβ (Rarβ) 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. |
| Databáze: | OpenAIRE |
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