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The mechanism of the chicken cleft primary palate mutation : subtitle altered Fgf8 signalling from frontonasal mass epithelium redirects proximodistal outgrowth of the upper beak Macdonald, Mary
Abstract
Facial development occurs through the outgrowth and fusion of neural crest-derived facial prominences that surround the primitive oral cavity. Failure of the prominences to grow together properly can result in a number of facial deformities, of which cleft lip with or without cleft palate is the most common. A mutation known as cleft primary palate (cpp) has been discovered in the chicken that causes complete failure of outgrowth of the upper facial prominences with the consequence that a bilateral cleft lip is formed. A series of grafting experiments showed that the mutation affects the frontonasal mass but not other facial prominences. Recombination experiments showed the growth of cpp mutant frontonasal mass mesenchyme is restored by recombination with wild-type epithelium. In contrast, the growth of normal craniofacial mesenchyme is not supported by cpp mutant frontonasal mass epithelium, implying that the mutation primarily affects the epithelium and not the mesenchyme. The failure of outgrowth is not due to a lack of skeletogenesis, since cartilage forms in all grafts containing cpp mutant tissue. Fgf8, which is usually restricted to the epithelium surrounding the nasal pits, was found throughout the frontonasal mass epithelium of stage 24 and 28 cpp mutant embryos. Expression of other genes localized to the frontonasal mass epithelium (Bmp4, Noggin and Shh) or in the frontonasal mass mesenchyme (Patched-1, Msxl, Msx2, AP2, type II collagen) was the same as in normal embryos. Programmed cell death in the cpp mutant frontonasal mass also did not differ from the normal. Cell proliferation, however, was increased in the mesenchyme underlying the ectopic Fgf8-expressing epithelium, leading to growth along the cranio-caudal rather than the proximo-distal axis. These results indicate that the failure of the cpp frontonasal mass to grow along a proximo-distal axis is due to a signalling defect in the epithelium. The cpp mutation is upstream of Fgf8, and ectopic Fgf8 expression may lead to the observed defect in signalling between the epithelium and the mesenchyme in the cpp frontonasal mass. The failure of outgrowth results in loss of the premaxilla and prenasal cartilage, and a bilateral cleft beak.
Item Metadata
Title |
The mechanism of the chicken cleft primary palate mutation : subtitle altered Fgf8 signalling from frontonasal mass epithelium redirects proximodistal outgrowth of the upper beak
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2002
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Description |
Facial development occurs through the outgrowth and fusion of neural crest-derived
facial prominences that surround the primitive oral cavity. Failure of the
prominences to grow together properly can result in a number of facial deformities, of
which cleft lip with or without cleft palate is the most common. A mutation known as
cleft primary palate (cpp) has been discovered in the chicken that causes complete failure
of outgrowth of the upper facial prominences with the consequence that a bilateral cleft
lip is formed. A series of grafting experiments showed that the mutation affects the
frontonasal mass but not other facial prominences. Recombination experiments showed
the growth of cpp mutant frontonasal mass mesenchyme is restored by recombination
with wild-type epithelium. In contrast, the growth of normal craniofacial mesenchyme is
not supported by cpp mutant frontonasal mass epithelium, implying that the mutation
primarily affects the epithelium and not the mesenchyme. The failure of outgrowth is not
due to a lack of skeletogenesis, since cartilage forms in all grafts containing cpp mutant
tissue. Fgf8, which is usually restricted to the epithelium surrounding the nasal pits, was
found throughout the frontonasal mass epithelium of stage 24 and 28 cpp mutant
embryos. Expression of other genes localized to the frontonasal mass epithelium (Bmp4,
Noggin and Shh) or in the frontonasal mass mesenchyme (Patched-1, Msxl, Msx2, AP2,
type II collagen) was the same as in normal embryos. Programmed cell death in the cpp
mutant frontonasal mass also did not differ from the normal. Cell proliferation, however,
was increased in the mesenchyme underlying the ectopic Fgf8-expressing epithelium,
leading to growth along the cranio-caudal rather than the proximo-distal axis. These
results indicate that the failure of the cpp frontonasal mass to grow along a proximo-distal
axis is due to a signalling defect in the epithelium. The cpp mutation is upstream of Fgf8,
and ectopic Fgf8 expression may lead to the observed defect in signalling between the
epithelium and the mesenchyme in the cpp frontonasal mass. The failure of outgrowth
results in loss of the premaxilla and prenasal cartilage, and a bilateral cleft beak.
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Extent |
10277934 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-10-02
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0090674
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2002-11
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.