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Disruption of the creb3l1 gene causes defects in caudal fin regeneration and patterning in zebrafish Danio rerio
Peyton E VanWinkle1, Eunjoo Lee1, Bridge Wynn1
1Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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.
Insights
Creb3l1 deficiency in zebrafish does not affect bone density but impairs caudal fin regeneration. This study reveals a new role for Creb3l1 in tissue growth and patterning during regeneration.
Area of Science:
- Developmental Biology
- Regenerative Medicine
- Genetics
Background:
- The gene cAMP-Responsive Element Binding protein 3-like-1 (CREB3L1) is linked to bone development issues in mammals.
- CREB3L1 mutations are associated with osteogenesis imperfecta in humans.
- The precise mechanism of CREB3L1 in bone development remains unclear.
Purpose of the Study:
- To investigate the physiological role of Creb3l1 using a zebrafish model.
- To understand Creb3l1's function in tissue regeneration.
Main Methods:
- CRISPR-Cas9 genome editing was used to create Creb3l1-deficient zebrafish.
- Skeletal morphology, bone density, and caudal fin regeneration were analyzed in mutant fish.
- Gene expression patterns, including Sonic Hedgehog signaling pathway components, were examined.
Main Results:
- Creb3l1-deficient zebrafish showed normal skeletal morphology and bone density.
- Fin regeneration was impaired, with reduced regenerate area and mineralized bone.
- Patterning defects, including decreased bifurcation complexity and distalization, were observed during fin regeneration.
- Aberrant patterning of shha and ptch2 genes was noted, suggesting a link to Sonic Hedgehog signaling.
Conclusions:
- Creb3l1 plays a novel role in regulating tissue growth and patterning during regeneration.
- The findings highlight a distinct function of Creb3l1 in zebrafish fin regeneration compared to its role in mammalian bone development.
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