PUBLICATION
Disruption of the creb3l1 gene causes defects in caudal fin regeneration and patterning in zebrafish Danio rerio
- Authors
- VanWinkle, P.E., Lee, E., Wynn, B., Nawara, T.J., Thomas, H., Parant, J., Alvarez, C., Serra, R., Sztul, E.
- ID
- ZDB-PUB-240715-1
- Date
- 2024
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 253(12): 1106-1129 (Journal)
- Registered Authors
- Parant, John, Thomas, Holly R.
- Keywords
- proximo‐distal axis, ptch2, runx2a, shha, zebrafish; creb3l1; fin bifurcation; fin regeneration
- MeSH Terms
-
- Osteogenesis/genetics
- Osteogenesis/physiology
- Body Patterning/genetics
- Zebrafish*/genetics
- Cyclic AMP Response Element-Binding Protein/genetics
- Cyclic AMP Response Element-Binding Protein/metabolism
- Animals
- Regeneration/genetics
- Regeneration/physiology
- Animal Fins*/physiology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- CRISPR-Cas Systems
- PubMed
- 39003620 Full text @ Dev. Dyn.
Citation
VanWinkle, P.E., Lee, E., Wynn, B., Nawara, T.J., Thomas, H., Parant, J., Alvarez, C., Serra, R., Sztul, E. (2024) Disruption of the creb3l1 gene causes defects in caudal fin regeneration and patterning in zebrafish Danio rerio. Developmental Dynamics : an official publication of the American Association of Anatomists. 253(12):1106-1129.
Abstract
Background The gene cAMP-Responsive Element Binding protein 3-like-1 (CREB3L1) has been implicated in bone development in mice, with CREB3L1 knock-out mice exhibiting fragile bones, and in humans, with CREB3L1 mutations linked to osteogenesis imperfecta. However, the mechanism through which Creb3l1 regulates bone development is not fully understood.
Results To probe the role of Creb3l1 in organismal physiology, we used CRISPR-Cas9 genome editing to generate a Danio rerio (zebrafish) model of Creb3l1 deficiency. In contrast to mammalian phenotypes, the Creb3l1 deficient fish do not display abnormalities in osteogenesis, except for a decrease in the bifurcation pattern of caudal fin. Both, skeletal morphology and overall bone density appear normal in the mutant fish. However, the regeneration of caudal fin postamputation is significantly affected, with decreased overall regenerate and mineralized bone area. Moreover, the mutant fish exhibit a severe patterning defect during regeneration, with a significant decrease in bifurcation complexity of the fin rays and distalization of the bifurcation sites. Analysis of genes implicated in bone development showed aberrant patterning of shha and ptch2 in Creb3l1 deficient fish, linking Creb3l1 with Sonic Hedgehog signaling during fin regeneration.
Conclusions Our results uncover a novel role for Creb3l1 in regulating tissue growth and patterning during regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping