Abelson Interactor 1 (Abi1) and Its Interaction with Wiskott-Aldrich Syndrome Protein (Wasp) Are Critical for Proper Eye Formation in Xenopus Embryos

• Published in: The Journal of biological chemistry 2013-05, Vol.288 (20), p.14135-14146
• Main Authors: Singh, Arvinder, Winterbottom, Emily F., Ji, Yon Ju, Hwang, Yoo-Seok, Daar, Ira O.
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - metabolism; Adaptor Proteins, Signal Transducing - chemistry; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adaptor Proteins, Signal Transducing - physiology; Animals; Cell Lineage; Cell Migration; Cell Movement; Development; Developmental Biology; Eye; Eye - embryology; Gene Expression Regulation, Developmental; Open Reading Frames; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Retina - embryology; Signal Transduction; src Homology Domains; Stem Cells - cytology; Wiskott-Aldrich Syndrome Protein - metabolism; Xenopus; Xenopus - embryology; Xenopus - genetics; Xenopus Proteins - chemistry; Xenopus Proteins - physiology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.445643

Abl interactor 1 (Abi1) is a scaffold protein that plays a central role in the regulation of actin cytoskeleton dynamics as a constituent of several key protein complexes, and homozygous loss of this protein leads to embryonic lethality in mice. Because this scaffold protein has been shown in cultured cells to be a critical component of pathways controlling cell migration and actin regulation at cell-cell contacts, we were interested to investigate the in vivo role of Abi1 in morphogenesis during the development of Xenopus embryos. Using morpholino-mediated translation inhibition, we demonstrate that knockdown of Abi1 in the whole embryo, or specifically in eye field progenitor cells, leads to disruption of eye morphogenesis. Moreover, signaling through the Src homology 3 domain of Abi1 is critical for proper movement of retinal progenitor cells into the eye field and their appropriate differentiation, and this process is dependent upon an interaction with the nucleation-promoting factor Wasp (Wiskott-Aldrich syndrome protein). Collectively, our data demonstrate that the Abi1 scaffold protein is an essential regulator of cell movement processes required for normal eye development in Xenopus embryos and specifically requires an Src homology 3 domain-dependent interaction with Wasp to regulate this complex morphogenetic process. Background: The Abi1 scaffold protein affects cell migration in vitro by regulating actin cytoskeletal dynamics. Results: Knockdown of Abi1 or its binding partner, Wasp, disrupts eye development and retinal progenitor cell movement in Xenopus embryos. Conclusion: Abi1 and Wasp are essential for eye morphogenesis in Xenopus. Significance: Cytoskeletal regulation by Abi1 is critical in vivo for morphogenesis during embryonic development.