A PAK family kinase and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration

• 成果类型: Article
• 署名作者: Doddihal, Viraj; Mann Jr, Frederick G.; Ross, Eric J.; McKinney, Mary C.; Guerrero-Hernandeza, Carlos; Brewster, Carolyn E.; McKinney, Sean A.; Alvarado, Alejandro Sanchez
• 署名单位: Stowers Institute for Medical Research
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9791
• DOI: 10.1073/pnas.2321919121
• 发表日期: 2024-05-14
• 关键词: planarian regeneration; cell-proliferation; protein-kinases; hippo pathway; organ size; stem-cells; yap; ORGANIZATION; polarity; GROWTH

摘要

Successful regeneration of missing tissues requires seamless integration of positional information along the body axes. Planarians, which regenerate from almost any injury, use conserved, developmentally important signaling pathways to pattern the body axes. However, the molecular mechanisms which facilitate cross talk between these signaling pathways to integrate positional information remain poorly understood. Here, we report a p21- activated kinase ( smed-pak1 ) which functionally integrates the anterior-posterior (AP) and the medio- lateral (ML) axes. pak1 inhibits WNT/(3- catenin signaling along the AP axis and, functions synergistically with the (3- catenin- independent WNT signaling of the ML axis. Furthermore, this functional integration is dependent on warts and merlin-the components of the Hippo/Yorkie (YKI) pathway. Hippo/YKI pathway is a critical regulator of body size in flies and mice, but our data suggest the pathway regulates body axes patterning in planarians. Our study provides a signaling network integrating positional information which can mediate coordinated growth and patterning during planarian regeneration.