Abstract
Zebrafish possess a remarkable ability to regenerate complicated structures by formation of a mass of undifferentiated mesenchymal cells called blastema. To understand how the blastema retains the original structural form, we investigate cellular transitions and transcriptional characteristics of cell identity genes during all stages of regeneration of an amputated lower jaw. We find that mesenchymal blastema originates from multiple sources including nucleated blood cells, fibroblasts, damaged muscle cells and pigment cells. These cells are transformed into two populations of blastemal progenitors: foxi1-expression and isl1-expression, before giving rise to cartilage, bone, and muscle. Time point- based transcriptomal analysis of 45 annotated Hox genes reveal that five 3′-end Hox genes and an equal number of 5′-end Hox genes are activated largely at the stage of blastema reformation. RNA in situ hybridization shows that foxi1 and pax3a are respectively expressed in the presumptive mandible skeletal region and regenerating muscle at 5 dpa. In contrast, hoxa2b and hoxa11b are widely expressed with different domain in chondrogenic blastema and blastema mesenchyme. Knockdown foxi1 changes the expression patterns of sox9a and hoxa2b in chondrogenic blastema. From these results we propose that two origins of blastemal progenitors define blastema skeleton and muscle respecifications through distinct signaling pathways. Meanwhile, the positional identity of blastema reformation is implicated in mesenchymal segmentation and characteristic expression pattern of Hox genes.
Highlights
Physiological wound healing is an intricate process by which the cells in the body regenerate and repair damaged living tissue to normal function
The zebrafish lower jaw consists of the mandible, hyoid apparatus and all the attached mandibular muscles (Mm) and other connective tissues
In the uncut fish we could not detect expression of sox9a mRNA signals a weak and discrete expression of foxi1 was detectable (Figure S3). These results suggest that two origins of blastemal progenitors define two different respecification fates: cranial skeletal regeneration mediated by foxi1-sox9a pathways and muscle regeneration by isl1-pax3a pathways
Summary
Physiological wound healing is an intricate process by which the cells in the body regenerate and repair damaged living tissue to normal function. Most tissues and body parts can heal by regeneration (the necrotic cells are replaced by the same tissue as was originally there) and/or by repair (injured tissue is replaced with scar tissue). Understanding the cellular and molecular responses in regenerating complicated structures in fish will eventually provide novel insights to promote tissue and organ regeneration in mammals and humans [3]. The third mechanism closely matches blastema formation, a mass of cells capable of growth and regeneration into organs or body parts [9]. The majority of published studies suggest that the dedifferentiation of mesodermal tissues contributes to limb and fin blastema formation [1], the cellular and molecular characteristics of blastemal cells are far less clear. Little is known about how the blastema reestablishes structural form and appropriate tissue polarity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
