Linking new genes to an odontogenesis TP63-mediated gene regulatory network that is peripheral to jaw morphogenesis
Date
2018-02-27
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
0000-0002-6240-7012
Type
Thesis
Degree Level
Masters
Abstract
Despite that teeth and jawbones can develop and evolve independently of each other, the
genetic processes that independently regulate cranial and dental morphogenesis remain unclear.
Previous microarray screens indicated that a TP63-mediated gene regulatory network is integral
to odontogenesis but peripheral to jaw morphogenesis.
Here, I characterized the expression of four genes flagged by our lab’s previous
microarray screens, comparing embryonic wild-type and TP63-null (TP63-/-) mutant mouse
mandible prominences. I hypothesized that in the normal dental epithelium, TP63 up-regulates
Fermt1 and Pltp and down-regulates Cbln1 and Krt8.
I validated the expression domains of these genes in TP63-/- mutant and wild-type mice
using RNA in-situ hybridization on paraffin tissue sections at two stages, E11.5, just after
odontogenesis begins, and at E13.5, just after odontogenesis arrests in the TP63-/- mutant.
My in situ results validated our lab’s previous microarray screens. My work revealed that Fermt1
is expressed in wild-type oral epithelium and dental epithelium, and that Pltp is expressed in
dental epithelium. Compared to wild-type littermates, in TP63-/- mice, Fermt1 and Pltp
expression intensity in the dental epithelium was decreased. Cbln1 was not expressed in wildtype
dental epithelium, although it expressed intensely in the dental epithelium of TP63-/-
littermates. Krt8 was expressed in the dental epithelium of both wild-type and TP63-/- embryos,
with increased intensity in the TP63-/- mice. In sum, my results largely supported my hypothesis.
As such, I propose that Fermt1, Pltp, Cbln1, and Krt8 belong to a TP63-mediated gene
regulatory network and co-regulate odontogenesis by mediating cell adhesion, cell signaling, and
epithelial-mesenchymal interactions at early stages of tooth development.
Description
Keywords
Odontogenesis, TP63, Gene regulatory network
Citation
Degree
Master of Science (M.Sc.)
Department
Anatomy and Cell Biology
Program
Anatomy and Cell Biology