Applicability of Zebrafish experimental model for

research in dentistry – A review

WHAT IS ZEBRAFISH? HUMANS AND ZEBRAFISH: SIMILARITIES ZEBRAFISH: DENTISTRY AND RELATED STUDIES
Danio rerio, commonly known as
1. The craniofacial mesenchyme is derived from migratory neural crest cells  Studies on zebrafish have discovered that the zebrafish has similar
zebrafish is a tropical fish native to
and paraxial mesoderm similar to that in humans (1). signalling and transcription pathways as humans. Research in
southeast Asia. About 2.5 to 4cm
long, it is an excellent test subject zebrafish has led to the conclusion that blocking of FGF signalling
and is used in many labs to replace results in arrest of primary tooth formation (5,6). It also verified that
Paraxial mesoderm
or to supplement higher vertebrate Paraxial mesoderm over expression of FGF ligands resulted in supernumerary teeth (6).
models.  A study by Liu et al., demonstrated that PITX2 transcription pathway
Cranial neural crest
Cranial neural crest cells cells deficiency lead to abnormal ocular and craniofacial development (7).
 Preclinical anti cancer drug screenings carried out in zebrafish makes
WHY ZEBRAFISH? Fig.1. Human skull Fig.2. Larval zebrafish skull it an applicable model for drug discovery and modification (8).
Fig.2. Zebrafish skull  Studies have been conducted on zebrafish to find the phenotypic
• Zebrafish is a fresh water teleost 2. Posterior end of Meckel’s cage and palatoquadrate are evolutionary variability in human birth defects. A study on foetal alcohol spectrum
living in conditions that can be homologous to malleus and incus of mammalian middle ear. disorders in zebrafish established that PDGFRA and ethanol interact to
easily replicated ex-situ. Hyomandibula in zebrafish is equivalent of mammalian stapes (inner ear). cause craniofacial abnormalities (9).
• Easily available and cost effective. The connection between hyomandibula and otic cartilage in fish represents  Treacher Collin’s syndrome, Charge syndrome, Roberts syndrome
• Zebrafish exhibits external the attachment of stapes to the oval window in the otic capsule in humans. have all been successfully modelled on zebrafish. These disorders
fertilization and embryo Anterior end of zebrafish neurocranium is homologous to mammalian hard comprise of cleft palate, microcephaly, smooth philtrum and other
development. palate (2). malformities (9,10).
• The teleost produces a great  Under dental applicability, Makkar et al, studied the in vivo molecular
number of progeny. The size of toxicity profile of dental materials MTA and biodentin using zebrafish
the egg is small and the embryos models (11).
being translucent makes  Zhao et al., evaluated the effects of various metal alloy shells of PFM
experimental manipulations such crowns on development of zebrafish embryos and larvae to determine
as cell labelling, lineage tracing the safety of these materials (12).
and cell transplantation  The teeth in zebrafish larvae were treated with fluorine to examine and
significantly smooth. compare the prevalence of dental fluorosis in primary and permanent
teeth (13).
The zebrafish has been a subject of many developmental studies,
Fig.3. Homology between zebrafish and human calvaria [2]
focusing mostly on embryonic development, a few on post-embryonic
3. The specialised diphyodont and heterodont dentition of human a has been studies on dentition. The results of these studies on zebra fish models
derived from the polyphyodonty homodont dentition in teleost. have been incorporated in this review report. This provides a hope for
novel studies which can be explored with respect to dentistry that can
become worthwhile for human race.

REFERENCES
Fig.5. See through zebrafish larvae 1) Yelick P. Schilling T. Molecular dissection of craniofacial development using zebrafish, Crit Rev Oral Biol Med 2002, 13(4).
2) Hendee K. Sorokina E. et al, PITX2 deficiency and associated human disease: insights from the zebrafish model, Human molecular
offer clues to birth defects. genetics, 2018, 27.
Fig.4. Teeth. a) enamel coating b) dentine layer c) pulp core (3) 3) Menke A, Spitsbergen J. et al Normal anatomy and histology of adult zebrafish, Toxicologic pathology, 2011, 39.
4) Howe K. Clark M, The zebrafish reference genome sequence and its relationship to the human genome, Nature, 2014, 505.
• Unlike higher organisms the organ 5) Jackman W. Draper B. et al, FGF signalling is required for zebrafish tooth development, Developmental biology, 2004, 274.
6) Klein O. Oberoi S. et al, Developmental disorders of the dentition, American journal of medical genetics part C, 2013, 163C.
system in zebrafish is highly 7) Liu Y. Semina E. PITX2 deficiency results in abnormal ocular and craniofacial development in zebrafish, PLoS one, 2012, 7.
4. Zebrafish share about 70% of genes with us. Almost 84% of the human 8) Jung D. Oh E. et al. A novel zebrafish human tumor xenograft model validated for anticancer drug screening, Molecular biosystems,2012, 8
minimalistic.
genes associated with diseases have a zebrafish counterpart (4). The 9) Mccarthy N. Wetherill L. et al. Pdgfra protects against ethanol induced craniofacial defects in a zebrafish model of FASD, Development,
• There is continuous tooth 2013, 140.
zebrafish genes and mutations can be compared with their orthologous 10) Balow A. Pierce L. Knockdown of fbxl10/kdm2bb rescues chd7 morphant phenotype in a zebrafish model of CHARGE syndrome,
regeneration in zebrafish giving CrossMark, 2013.
human genes so as to study biological phenomena such as organogenesis,
us a better understanding of tooth 11) Makkar H. Verma S.K. In vivo molecular toxicity profile of dental bioceramics in embryonic zebrafish, Chemical research in toxicology, 2018,
developmental and physiological defects and related diseases. 31(9).
replacement in mammals. 12) Zhao L. Si J. Toxicity of porcelain fused to metal substrate to zebrafish embryos and larvae, Life sciences, 2018, 203.
13) Zhang Y. Zhang Y, et al. Grading and quantification of dental fluorosis in zebrafish larva, CrossMark, 2016.