Morphogen-based simulation model of ray growth and joint patterning during fin development and regeneration

Abstract

SUMMARYThe fact that some organisms are able to regenerate organs of the correct shape and size following amputation is particularly fascinating, but the mechanism by which this occurs remains poorly understood. The zebrafish (Danio rerio) caudal fin has emerged as a model system for the study of bone development and regeneration. The fin comprises 16 to 18 bony rays, each containing multiple joints along its proximodistal axis that give rise to segments. Experimental observations on fin ray growth, regeneration and joint formation have been described, but no unified theory has yet been put forward to explain how growth and joint patterns are controlled. We present a model for the control of fin ray growth during development and regeneration, integrated with a model for joint pattern formation, which is in agreement with published, as well as new, experimental data. We propose that fin ray growth and joint patterning are coordinated through the interaction of three morphogens. When the model is extended to incorporate multiple rays across the fin, it also accounts for how the caudal fin acquires its shape during development, and regains its correct size and shape following amputation.

Keeping at Arm’s Length during Regeneration

“…It should be noted that Calcineurin may now be added to a growing list of inhibitory signals key to proper regeneration, that includes secreted Wnt signaling inhibitors (Kang et al, 2013; Stoick-Cooper et al, 2007), in addition to more often-studied positive regulators. These negative regulators can now be incorporated into regularly updated molecular or mathematical models for growth control during fin regeneration (Rolland-Lagan et al, 2012; Stewart et al, 2014; Wehner et al, 2014). …”

Segmentation pattern of zebrafish caudal fin is affected by developmental temperature and defined by multiple fusions between segments

“…Within a single lepidotrichium, segment length decreases from the proximal to the distal positions (Iovine & Johnson, ). Concerning the between lepidotrichia variation, lobe lepidotrichia presents longer and more numerous segments than the cleft lepidotrichia (Goldsmith et al, ; Haas, ; Rolland‐Lagan et al, ). The results of the current study agree with the previous studies on the size variation of segments.…”

“…The growth of each lepidotrichium is achieved by the addition of new segments at its distal tip (Haas, ), with the segment number increasing as a function of body size (Iovine & Johnson, ). Growth and regeneration mechanisms of caudal‐fin lepidotrichia have been extensively studied in the past (e.g., Akimenko, Mari‐Beffa, Becerra, & Geraudie, ; Azevedo, Sousa, Jacinto, & Saude, ; Goldsmith, Iovine, O’Reilly‐Pol, & Johnson, ; Iovine, ; Jain, Stroka, Yan, Huang, & Iovine, ; Johnson & Bennett, ; Mari‐Beffa, Palmqvist, Marin‐Giron, Montes & Becerra, ; Rolland‐Lagan, Paquette, Tweedle, & Akimenko, ; van Eeden et al, ). On the contrary, to our knowledge, studies on the plasticity of this complex structure are limited to the effects of environment on the whole fin size (e.g., Imre, McLaughlin, & Noakes, ; Laporte, Claude, Berrebi, Perret, & Magnan, ).…”

An amputation resets positional information to a proximal identity in the regenerating zebrafish caudal fin

“…In fact, a crosstalk between blastema, distal epidermis and inter-ray tissue was demonstrated to be essential to signal the formation of a bifurcation in regenerating zebrafish fins [8]. More recently, a mathematical model proposes that the regeneration of a fin with the correct shape and pattern requires the interplay of three morphogens [22]. Future studies will be essential to uncover the signals that give positional information to the regenerating fin/intact fin tissue.…”