期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 45, 页码 12027-12032出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1710254114
关键词
phosphorylation; cell signaling; cytokines; surface receptors; pigment development
资金
- NIGMS NIH HHS [T32 GM007324] Funding Source: Medline
Anaplastic lymphoma kinase (Alk) and leucocyte tyrosine kinase (Ltk) were identified as orphan receptor tyrosine kinases (RTKs) with oncogenic potential. Recently ALKAL1 and ALKAL2 (also named augmentor-beta and augmentor-alpha or FAM150A and FAM150B, respectively) were discovered as physiological ligands of Alk and Ltk. Here, we employ zebrafish as a model system to explore the physiological function and to characterize in vivo links between Alk and Ltk with their ligands. Unlike the two ligands encoded by mammalian genomes, the zebrafish genome contains three genes: aug-alpha 1, aug-alpha 2, and aug-beta. Our experiments demonstrate that these ligands play an important role in zebrafish pigment development. Deficiency in aug-alpha 1, aug-alpha 2, and aug-beta results in strong impairment in iridophore patterning of embryonic and adult zebrafish that is phenocopied in zebrafish deficient in Ltk. We show that aug-alpha 1 and aug-alpha 2 are essential for embryonic iridophore development and adult body coloration. In contrast, aug-alpha 2 and aug-beta are essential for iridophore formation in the adult eye. Importantly, these processes are entirely mediated by Ltk and not by Alk. These experiments establish a physiological link between augmentor ligands and Ltk and demonstrate that particular augmentors activate Ltk in a tissue-specific context to induce iridophore differentiation from neural crest-derived cells and pigment progenitor cells.
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