Glial cell ecology in zebrafish development and regeneration

Abstract

Zebrafish have been found to be the premier model organism in biological and biomedical research, specifically offering many advantages in developmental biology and genetics. The zebrafish (Danio rerio) has the ability to regenerate its spinal cord after injury. However, the complete molecular and cellular mechanisms behind glial bridge formation in zebrafish remains unclear. In our review paper, we examine the extracellular and intracellular molecular signaling factors that control zebrafish glial cell bridging and glial cell development in the forebrain. The interplay between initiating and terminating molecular feedback cycles deserve future investigations during glial cell growth, movement, and differentiation.

Keywords: Cell biology; Developmental biology; Fgf signaling; Genetics; Glial bridge; Molecular biology; Neuroscience; Zebrafish; ctgfa; shh; slit2/3.

Figure 1

Cell Ecology Framework during Zebrafish Spinal Cord Regeneration. An ecological framework integrating extracellular chemotactic cues and cell signaling (magenta circle) that control growth (orange circle), cell movement (blue circle), and cell differentiation (green circle) during zebrafish spinal cord regeneration. Feedback mechanisms help maintain molecular and cellular homeostasis during regeneration (black arrows).

Figure 2

Feedback Cycles in Glial Cell Development and Regeneration. (A-B) Molecular positive and negative feedback cycles that govern zebrafish glial cell bridging in the spinal cord upon injury (A) and zebrafish glial cell connections in the developing zebrafish forebrain (B). Within each molecular feedback cycle, positive feedback arrow (green arrow) and negative feedback (or feedback inhibition) arrow (red arrow) are depicted for each process. Molecular positive feedback factors (green ‘go’ signal) and termination signals (red ‘stop’ signal) are indicated along with unknown factors listed as question marks. ‘Go’ signals include ctgfa, Fgf, and Wnt/β-catenin activating Collagen XIII (Wnt ColXIII). Dkk1 overexpression (Dkk1 O.E.), glucocorticoid signaling through receptor Nr3c1 (G.C. Nr3c1), and overexpression of Axin 1 (Axin 1 O.E.) are termination signal during zebrafish glial bridge formation in spinal cord in response to injury. Extracellular signals that act as termination factors remain area for future investigations (ECM red ‘stop’ signal).