Growth arrest-specific 2-like 3 (Gas2l3) is a newly discovered cell cycle protein and a cytoskeleton orchestrator that binds both actin filament and microtubule networks. Studies of cultured mammalian cells established Gas2l3 as a regulator of the cell division process, in particular cytokinesis and cell abscission. Thus far, the role of Gas2l3 in vivo remains entirely unknown. In order to investigate Gas2l3 in developing vertebrates, we cloned the zebrafish gene. Spatiotemporal analysis of gas2. l3 expression revealed a ubiquitous maternal transcript as well as a zygotic transcript primarily restricted to brain tissues. We next conducted a series of loss-of-function experiments, and searched for developmental anomalies at the end of the segmentation period. Our analysis revealed abnormal brain morphogenesis and ventricle formation in gas2. l3 knockdown embryos. This signature phenotype could be rescued by elevated levels of gas2. l3 RNA. At the tissue level, gas2. l3 downregulation interferes with cell proliferation, suggesting that the cell cycle activities of Gas2l3 are essential for brain tissue homeostasis. Altogether, this study provides the first insight into the function of gas2. l3 in vivo, demonstrating its essential role in brain development.
|Number of pages||9|
|State||Published - 15 Oct 2014|
Bibliographical noteFunding Information:
We are deeply indebted to Dr. Adi Inbal for her critical input throughout this work, and to Prof. Hazel Sive for her important comments at the early stages of this research. We also thank Dr. Gad Vatin and Mr. David Zada for their immense technical assistance throughout this study, Dr. Rachel Levy-Drummer for statistical consulting and Ms. Sharon Victor for copy-editing. This work was funded by the Israeli Centers of Research Excellence (I-CORE), Gene Regulation in Complex Human Disease, Center no. 41/11 (AT), Israel Cancer Association Grant 20120067 (AT), and Marie Curie Actions-International Reintegration Grant FP7- PEOPLE-2010-RG, 274333 (LA).
© 2014 Elsevier Inc.
- Brain morphogenesis
- Cell proliferation