Genetic approaches to study liver development in zebrafish - Core component sec13 in COPII complex is essential for liver development in zebrafish

Abstract

The liver is one of the largest internal organs and plays many essential functions in the body. However, its embryonic developmental process is currently poorly studied, especially regarding through forward genetic approaches. We use zebrafish as the model to study liver development. Through screening mutagenized zebrafish populations, 15 putative liver defective mutants were identified. Positional cloning was successfully performed on the mutant line m198 and revealed that the genetic lesion in m198 was a thymine to adenine transversion in sec13, a key component of the COPII complex which involves in protein transportation from the endoplasmic reticulum (ER) to the Golgi apparatus. Mechanism study revealed that Sec13m198 is Carboxyl-terminus truncated and failed to interact with Sec31A, its essential partner in forming the COPII transport vesicle. We propose that this loss-of-interaction leads to the growth arrest in the mutant liver, as well as other digestive organs and skeleton cartilage, in which both Sec13 and Sec31A express at high level.