Identification and functional analysis of novel facial patterning genes in the duplicated beak chicken embryo

Autor: Iva Vesela, Alexander J. Trachtenberg, Suresh Nimmagadda, Winston Patrick Kuo, Sara Hosseini-Farahabadi, Marcela Buchtová, Joy M. Richman, Poongodi Geetha-Loganathan, Katherine Fu
Rok vydání: 2015
Předmět:
TBX22
Retinoic acid
Chick Embryo
Microarray
Animals
Genetically Modified
Craniofacial
chemistry.chemical_compound
0302 clinical medicine
Cranial neural crest
Databases
Genetic
Maxilla
In Situ Hybridization
Oligonucleotide Array Sequence Analysis
Genetics
0303 health sciences
Beak
Wnt signaling pathway
Rspondin
Gene Expression Regulation
Developmental
Neural crest
Cell biology
Maxillary prominence
Bone Morphogenetic Proteins
embryonic structures
Signal Transduction
Quality Control
Proteinase Inhibitory Proteins
Secretory
Tretinoin
Biology
Real-Time Polymerase Chain Reaction
Bone morphogenetic protein
03 medical and health sciences
Noggin
Animals
Molecular Biology
Body Patterning
030304 developmental biology
Cleft lip
Gene Expression Profiling
Chicken embryo
Cell Biology
chemistry
Face
Carrier Proteins
030217 neurology & neurosurgery
Peptidase Inhibitor 15
Developmental Biology
Zdroj: Developmental Biology. 407:275-288
ISSN: 0012-1606
DOI: 10.1016/j.ydbio.2015.09.007
Popis: Cranial neural crest cells form the majority of the facial skeleton. However exactly when the pattering information and hence jaw identity is established is not clear. We know that premigratory neural crest cells contain a limited amount of information about the lower jaw but the upper jaw and facial midline are specified later by local tissue interactions. The environmental signals leading to frontonasal identity have been explored by our group in the past. Altering the levels of two signaling pathways (Bone Morphogenetic Protein) and retinoic acid (RA) in the chicken embryo creates a duplicated midline on the side of the upper beak complete with egg tooth in place of maxillary derivatives (Lee et al., 2001). Here we analyze the transcriptome 16h after bead placement in order to identify potential mediators of the identity change in the maxillary prominence. The gene list included RA, BMP and WNT signaling pathway genes as well as transcription factors expressed in craniofacial development. There was also cross talk between Noggin and RA such that Noggin activated the RA pathway. We also observed expression changes in several poorly characterized genes including the upregulation of Peptidase Inhibitor-15 (PI15). We tested the functional effects of PI15 overexpression with a retroviral misexpression strategy. PI15 virus induced a cleft beak analogous to human cleft lip. We next asked whether PI15 effects were mediated by changes in expression of major clefting genes and genes in the retinoid signaling pathway. Expression of TP63, TBX22, BMP4 and FOXE1, all human clefting genes, were upregulated. In addition, ALDH1A2, ALDH1A3 and RA target, RARβ were increased while the degradation enzyme CYP26A1 was decreased. Together these changes were consistent with activation of the RA pathway. Furthermore, PI15 retrovirus injected into the face was able to replace RA and synergize with Noggin to induce beak transformations. We conclude that the microarrays have generated a rich dataset containing genes with important roles in facial morphogenesis. Moreover, one of these facial genes, PI15 is a putative clefting gene and is in a positive feedback loop with RA.
Databáze: OpenAIRE
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