Maternal regulation of the vertebrate egg-to-embryo transition
Authors: Fuentes Ricardo , Marlow Florence L. , Abrams Elliott W. , Zhang Hong , Kobayashi Manami , Gupta Tripti , Kapp Lee D. , DiNardo Zachary , Heller Ronald , Cisternas Ruth , Montecinos-Franjola Felipe , Vought William , Mullins Mary C. 
Published: June 2023

Egg activation and early embryonic development are complex and highly regulated processes that involve a series of coordinated cellular and molecular events after fertilization. While significant progress has been made in unraveling the mechanisms underlying these processes, there remains a need to comprehensively understand the precise molecular pathways and regulatory factors involved. We characterized four recessive maternal-effect mutants identified from a zebrafish forward genetic screen that function during the egg-to-embryo transition. We found that these genes encompass distinct aspects of egg activation, including cortical granule biology, cytoplasmic segregation, and the suppression of microtubule organizing center (MTOC) assembly and ectopic aster-like microtubule formation. These genes are essential to the development of the early embryo and the establishment of the basic body plan. Notably, we discovered a novel gene that we namedkrang,which is highly conserved across metazoans. Maternal Krang was found to be associated with the function of cortical granules during egg activation. This collection of mutants represents valuable tools to understand the genetic architecture underlying phenotypic traits shaping the egg-to-embryo transition. Furthermore, these results highlight the evolutionary conservation of maternal functions in diverse species. By deepening our understanding of these findings, we will improve our knowledge of reproductive traits and potentially develop new diagnostic tools to address human reproductive disorders.

Author Summary

During egg activation, the egg undergoes a series of biochemical and cellular modifications that activate its dormant metabolism, preparing it to initiate embryonic development. Egg activation initiates the completion of meiosis, and the newly formed zygote undergoes a series of additional changes, including the cell cycle establishment. However, our knowledge of the molecular mechanisms controlling these processes remain limited. We identified four recessive maternal-effect mutants in zebrafish that exhibit a range of developmental alterations during egg activation and early embryogenesis. We found that these maternally acting mutant genes are associated with defects in cortical granule exocytosis, yolk-cytoplasm segregation, microtubule nucleation and dynamics that are critical for the egg-to-embryo transition. Our results suggest that the proper regulation of these processes is essential for successful egg development and embryogenesis. We characterized the Krang factor, which regulates aspects of egg activation likely by modulating the secretory pathway. Further studies on this gene may provide new insights into the molecular mechanisms underlying oocyte development and egg quality acquisition. Overall, our collection of maternal-effect mutants sheds light on the proper regulation of key molecular and cellular events for successful egg development, with important implications for reproductive medicine and assisted reproductive technologies.