Actinodin, fin-to-limb transition
The transition from fin-to-limb is regarded as a highly important evolutionary step in the colonization and diversification of all land species. Our lab has identified a gene family in zebrafish, termed actinodin (and), which codes for structural proteins in the teleost fin. These proteins are crucial for the formation of important skeletal elements known as actinotrichia. Interestingly, this gene family is absent from all tetrapod genomes examined to date. We have identified cis-regulatory elements driving tissue-specific actinodin1 expression in zebrafish embryonic fins. Analysis of these regulatory regions may provide insight into how shifts in and1 expression may have contributed to the loss of this gene family during the transition from fish to tetrapods.
5’HoxA/D functional analysis
Homeobox-containing (Hox) genes code for transcription factors that contribute to axial patterning of many structures during development, including fins and limbs. Using a variety of techniques, including CRISPR/cas9 and ectopic expression analysis, we are seeking to determine the role of multiple 5’HoxA/D genes during zebrafish fin development.
Our studies have been focused on the functional analysis of the hedgehog and bone morphogenetic signaling pathways during fin regeneration. We have shown that the hedgehog signaling pathway is involved in both growth of the fin regenerate and formation and patterning of the dermal bones composing the fin rays. We also showed that bmp signaling is both required for the growth of the regenerate and for the differentiation of the bone-secreting cells. This study and other studies also unraveled the surprising finding that fin rays described as dermal bones are expressing factors uniquely found in the cartilage leading to the formation of endochondral bone. These results position ray bone in an intermediate category between dermal and endochondral bone.
During zebrafish fin ray regeneration, bone segments are periodically added at the distal tips of each fin ray, each segment being separated by a joint. Joint formation involves the expression of a unique set of genes: hoxa13a, evx1, and pthlha. Bone formation occurs via intramembranous ossification and involves the expression of several bone markers: ihha, sp7, col10a and osc. The alternation between bone segment formation and joint formation during fin ray regeneration is regulated by the positional information relayed during regeneration. It has been suggested that the calcineurin and retinoic acid signaling pathways may provide the positional information that regulates joint and bone segment formation. We are currently exploring the potential role of hoxa13a as well as additional molecular markers in regulating joint positioning during fin ray regeneration.
Human disease Model Projects
Using zebrafish, we are creating models for human disease including Epidermolysis bullosa simplex (EBS), primary ciliary dyskinesia (PCD) and Laminopathies. We are hoping to gain a better insight into the molecular pathology of these diseases, and perform high throughput drug screens to identify compounds that eliminate/alleviate symptoms.