PUBLICATION
Knockdown of hspg2 is associated with abnormal mandibular joint formation and neural crest cell dysfunction in zebrafish
- Authors
- Castellanos, B.S., Reyes-Nava, N.G., Quintana, A.M.
- ID
- ZDB-PUB-210309-5
- Date
- 2021
- Source
- BMC Developmental Biology 21: 7 (Journal)
- Registered Authors
- Quintana, Anita
- Keywords
- Craniofacial development, HSPG2, Neural crest cells
- MeSH Terms
-
- Animals
- Dwarfism*
- Mandible
- Neural Crest
- Osteochondrodysplasias*
- Zebrafish/genetics
- PubMed
- 33678174 Full text @ BMC Dev. Biol.
Citation
Castellanos, B.S., Reyes-Nava, N.G., Quintana, A.M. (2021) Knockdown of hspg2 is associated with abnormal mandibular joint formation and neural crest cell dysfunction in zebrafish. BMC Developmental Biology. 21:7.
Abstract
Background Heparan sulfate proteoglycan 2 (HSPG2) encodes for perlecan, a large proteoglycan that plays an important role in cartilage formation, cell adhesion, and basement membrane stability. Mutations in HSPG2 have been associated with Schwartz-Jampel Syndrome (SJS) and Dyssegmental Dysplasia Silverman-Handmaker Type (DDSH), two disorders characterized by skeletal abnormalities. These data indicate a function for HSPG2 in cartilage development/maintenance. However, the mechanisms in which HSPG2 regulates cartilage development are not completely understood. Here, we explored the relationship between this gene and craniofacial development through morpholino-mediated knockdown of hspg2 using zebrafish.
Results Knockdown of hspg2 resulted in abnormal development of the mandibular jaw joint at 5 days post fertilization (DPF). We surmised that defects in mandible development were a consequence of neural crest cell (NCC) dysfunction, as these multipotent progenitors produce the cartilage of the head. Early NCC development was normal in morphant animals as measured by distal-less homeobox 2a (dlx2a) and SRY-box transcription factor 10 (sox10) expression at 1 DPF. However, subsequent analysis at later stages of development (4 DPF) revealed a decrease in the number of Sox10 + and Collagen, type II, alpha 1a (Col2a1a)+ cells within the mandibular jaw joint region of morphants relative to random control injected embryos. Concurrently, morphants showed a decreased expression of nkx3.2, a marker of jaw joint formation, at 4 DPF.
Conclusions Collectively, these data suggest a complex role for hspg2 in jaw joint formation and late stage NCC differentiation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping