Gene expression and Tooth Development

Question 1

transcriptional regulation

Answer 1

1) modification of DNA and regulation through transcription factors
2) histone acetylation/methylation
3) CpG sites methylation
4) TFs
- enhancer-activator
-silencer-repressor

Question 2

translational regulation

Answer 2

inactivation of initiation factors can prevent the ribosome from translating the mRNA

Question 3

histone acetylation

Answer 3

1) high transcriptional activity are loosely packed

Question 4

histone methylation

Answer 4

1) low or no transcriptional activity are densely packed

Question 5

availability of genes in eukaryotic chromosomes

Answer 5

1) enhancer region for structural gene must be exposed
2) transcription factors binds enhancer regions to promotes RNA polymerase binding and transcription at multiple sites
3) repressors inhibit by binding to silencer regions and block RNA polymerase

Question 6

post-transcriptional regulation

Answer 6

1) RNA processing
2) splicing
- removes noncoding introns
3) addition of CAP and poly A tail
- makes RNA more stable
3) RNA editing
- could change AA codons
4) microRNA
- small non-coding RNA (~22 nucleotides) and its function is to regulate gene expression

Question 7

microRNA formation

Answer 7

1) their genes are usually transcribed by RNA pol II
2) pri-miRNAs are primary transcripts
3) cleaved by microprocessor complex into ~85 nucleotide stem-loop structure
- pre-miRNA
4) pre-miRNAs are processed by RNase III enzyme Dicer in the cytoplasm
- ~20-22 nucleotide miRNA/miRNA duplex
5) after the duplex is unwound, the mature miRNA is incorporated into RISC protein
6) mediates gene silencing via mRNA cleavage and degradation or translational repression

Question 8

tooth development

Answer 8

1) communication between two tissues, epithelium and mesenchyme
- language is secreted signal molecules and GF

2) stages
- dental lamina, bud cap, cap stage, bell stage, and then eruption
3) teeth form from surface ectoderm of branchial arch I and frontonasal prominence and neural crest-derived mesenchyme

Question 9

signaling in tooth development

Answer 9

1) transforming GF (TGFbeta)
2) fibroblast GF (FGF)
3) Hedgehog (in tooth only sonic hedgehog, Shh)
4) Wnt

Question 10

TGFbeta

Answer 10

1) TGF-B is important in regulation of cell growth, differentiation, and development
2) both bone morphogenetic protein (BMP) and activin activate this pathway
3) SMAD proteins are signal transducers and transcriptional modulators

Question 11

WNT pathway

Answer 11

1) regulates stem cell pluripotency and cell fate decisions during development
2) WNT ligand is a glycoprotein that binds to frizzled receptors
3) Off state
- beta-catenin is phosphorylated by CK1 and APX/acin/GSK-3beta complex
- this leads to ubiquitination and degradation
4) ON state
- Wnt is present => binds frizzled
- activation of disheveled (Dvl), displacing GSK-3beta from APC/axin
- stabilized beta-catenin binds to LEF/TCF transcription factors, displacing co-repressors and recruiting additional co-activators to Wnt target genes

Question 12

hedgehog pathway

Answer 12

1) Hh is essential for embryonic development and adult tissue maintenance, renewal, and regeneration
2) Shh, a Hh ligand, is synthesized as a precursor protein, secreted by Dispatched
- Hh initiate signaling through binding to the canonical receptor Patched (PTCH1)

Question 13

epigenetics in tooth development

Answer 13

1) epigenetic regulation by DNA methylation, histone modification, or post-transcriptional regulation by Mi-RNAs could also be found in tooth development

Question 14

ectodermal dysplasia syndromes

Answer 14

1) conditions defined as two or more type of ectodermal organs are affected and dental defects include typically multiple missing teeth (oligodontia) as well as small and misshapen teeth
2) many genes have been identified in which mutations cause ectodermal dysplasia

Question 15

transcription factor p63

Answer 15

1) important gene regulating placode formation and expressing throughout the surface ectoderm
2) mutations in the transcription factor p63 cause the ECC syndrome featured by ectodermal dysplasia and ectrodactyly and cleft lip/palate
3) typical patient has a sever dental phenotype with multiple missing and misshapen teeth

Question 16

hypohidrotic ectodermal dysplasia (HED)

Answer 16

1) mutations in Eda pathway genes cause HED manifesting multiple missing teeth) has well as defects in other ectodermal organs (sparse hair, reduced sweating
2) ectodysplasin (Eda) is a signal of the tumor necrosis factor (TNF) family and signals through its receptor EdaR that is locally expressed in the placodes of all ectodermal appendages as well as in primary and secondary enamel knots

Question 17

dental tissue homeostasis and repair

Answer 17

1) various types of stem cells (PDLSCs, DPSCs, and SCAPs) can be found in the dental pulp and PDL around the root
2) mild injury induces reactionary dentinogenesis, which stimulates increased dentin secretion by odontoblasts
3) severe injury triggers reparative dentinogenesis, which recruits dental progenitors, which differentiate into odontoblast like cells to fuel dentin production
4) bioactive molecules released from mineralized dental tissues and GFs from inflammatory cells can promote odontogenesis and tissue repair