Meeting Abstract
At the head-trunk transition, alignment of hindbrain and spinal cord territories to occipital and cervical structures is critical for coherent organization of neural and skeletal systems. Changes in neural or mesodermal tissue configuration arising from defects in territory size specification, patterning or relative axial placement can severely compromise system integration and function. Here we show that neural and mesodermal tissue coordination at the zebrafish head-trunk transition critically depends on two novel activities of the signaling factor Retinoic Acid (RA) specifying the size and axial position of the hindbrain territory relative to mesodermal structures. These activities are each independent but coordinated with RA’s well-established function in hindbrain patterning. Using neural and mesodermal landmarks we demonstrate that RA function in aligning neural and mesodermal tissues temporally precedes the specification of hindbrain and spinal cord territories and the activation of hox transcription. Using cell transplantation assays we show that RA activity in the neuroepithelium is direct for hindbrain patterning but indirect for hindbrain territory size specification. This indirect function is independent of FGF and dependent on Wnts. Importantly, RA specifies and patterns the hindbrain territory by antagonizing the activity of the spinal cord specification gene cdx4; loss of Cdx4 rescues the defects associated with the loss of RA, including the reduction in hindbrain size and the loss of posterior rhombomeres. We propose that at the head-trunk transition, RA coordinates the specification, alignment and patterning of neural and mesodermal tissues essential for neural and skeletal system’s functional organization.
