TGFβ signaling is required for sclerotome resegmentation during development of the spinal column in Gallus gallus.

Abstract

We previously showed the importance of TGF{beta} signaling in development of the mouse axial skeleton. Here, we provide the first direct evidence that TGF{beta} signaling is required for resegmentation of the sclerotome using chick embryos. Lipophilic fluorescent tracers, DiO and DiD, were microinjected into adjacent somites of embryos treated with or without TGF{beta}R1 inhibitor, SB431542, at developmental day E2.5 (HH16). Lineage tracing of labeled cells was observed over the course of 4 days until the completion of resegmentation at E6.5 (HH32). Vertebrae were malformed and intervertebral discs were small and misshapen in SB431542 injected embryos. Hypaxial myofibers were also increased in thickness after treatment with the inhibitor. Inhibition of TGF{beta} signaling resulted in alterations in resegmentation that ranged between full, partial, and slanted shifts in distribution of DiO or DiD labeled cells within vertebrae. Patterning of rostro- caudal markers within sclerotome was disrupted at E3.5 after treatment with SB431542 with rostral domains expressing both rostral and caudal markers. We propose that TGF{beta} signaling regulates rostro-caudal polarity and subsequent resegmentation in sclerotome during spinal column development.