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Genetics. 2018 Jun;209(2):489-506. doi: 10.1534/genetics.118.300904. Epub 2018 Apr 20.

Regulation of Cell-to-Cell Communication and Cell Wall Integrity by a Network of MAP Kinase Pathways and Transcription Factors in Neurospora crassa.

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The Plant and Microbial Biology Department, University of California, Berkeley, California 94720-3102.
The Energy Biosciences Institute, University of California, Berkeley, California 94720-3102.
US Department of Energy, Joint Genome Institute, Walnut Creek, California 94598.
The Plant and Microbial Biology Department, University of California, Berkeley, California 94720-3102
Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720.


Maintenance of cell integrity and cell-to-cell communication are fundamental biological processes. Filamentous fungi, such as Neurospora crassa, depend on communication to locate compatible cells, coordinate cell fusion, and establish a robust hyphal network. Two MAP kinase (MAPK) pathways are essential for communication and cell fusion in N. crassa: the cell wall integrity/MAK-1 pathway and the MAK-2 (signal response) pathway. Previous studies have demonstrated several points of cross-talk between the MAK-1 and MAK-2 pathways, which is likely necessary for coordinating chemotropic growth toward an extracellular signal, and then mediating cell fusion. Canonical MAPK pathways begin with signal reception and end with a transcriptional response. Two transcription factors, ADV-1 and PP-1, are essential for communication and cell fusion. PP-1 is the conserved target of MAK-2, but it is unclear what targets ADV-1. We did RNA sequencing on Δadv-1, Δpp-1, and wild-type cells and found that ADV-1 and PP-1 have a shared regulon including many genes required for communication, cell fusion, growth, development, and stress response. We identified ADV-1 and PP-1 binding sites across the genome by adapting the in vitro method of DNA-affinity purification sequencing for N. crassa To elucidate the regulatory network, we misexpressed each transcription factor in each upstream MAPK deletion mutant. Misexpression of adv-1 was sufficient to fully suppress the phenotype of the Δpp-1 mutant and partially suppress the phenotype of the Δmak-1 mutant. Collectively, our data demonstrate that the MAK-1/ADV-1 and MAK-2/PP-1 pathways form a tight regulatory network that maintains cell integrity and mediates communication and cell fusion.


DAP-seq; MAP kinase; Neurospora crassa; cell fusion; cell-to-cell communication; regulatory networks

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