SummaryIn Aspergillus nidulans, asexual differentiation requires the presence of the transcription factor FlbB at the cell tip and apical nuclei. Understanding the relationship between these two pools is crucial for elucidating the biochemical processes mediating conidia production. Tip-to-nucleus communication was demonstrated by photo-convertible FlbB::Dendra2 visualization. Tip localization of FlbB depends on Cys382 in the C-terminus and the bZIP DNA-binding domain in the N-terminus. FlbE, a critical FlbB interactor, binds the bZIP domain. Furthermore, the absence of FlbE results in loss of tip localization but not nuclear accumulation. flbE deletion also abrogates transcriptional activity indicating that FlbB gains transcriptional competence from interactions with FlbE at the tip. Finally, a bipartite nuclear localization signal is required for nuclear localization of FlbB. Those motifs of FlbB may play various roles in the sequence of events necessary for the distribution and activation of this transcriptionally active developmental factor. The tip accumulation, FlbE-dependent activation, transport and nuclear import sketch out a process of relaying an environmentally triggered signal from the tip to the nuclei. As the first known instance of transcription factor-mediated tip-to-nucleus communication in filamentous fungi, this provides a general framework for analyses focused on elucidating the set of molecular mechanisms coupling apical signals to transcriptional events.

The infection cycle of filamentous fungi consists of two main stages: invasion (growth) and dispersion (development). After the deposition of a spore on a host, germination, polar extension and branching of vegetative cells called hyphae allow a fast and efficient invasion. Under suboptimal conditions, genetic reprogramming of hyphae results in the generation of asexual spores, allowing dissemination to new hosts and the beginning of a new infection cycle. In the model filamentous fungus Aspergillus nidulans, asexual development or conidiation is induced by the upstream developmental activation (UDA) pathway. UDA proteins transduce signals from the tip, the polarity site of hyphae, to nuclei, where developmental programs are transcriptionally activated. The present review summarizes the current knowledge on this tip-to-nucleus communication mechanism, emphasizing its dependence on hyphal polarity. Future approaches to the topic will also be suggested, as stimulating elements contributing to the understanding of how apical signals are coupled with the transcriptional control of development and pathogenesis in filamentous fungi.

Permanently polarized cells have developed transduction mechanisms linking polarity-sites with gene regulation in the nucleus. In neurons, one mechanism is based on long-distance retrograde migration of transcription factors (TFs). Aspergillus nidulans FlbB is the only known fungal TF shown to migrate retrogradely to nuclei from the polarized region of fungal cells known as hyphae. There, FlbB controls developmental transitions by triggering the production of asexual multicellular structures. FlbB dynamics in hyphae is orchestrated by regulators FlbE and FlbD. At least three FlbE domains are involved in the acropetal transport of FlbB, with a final MyoE/actin filament-dependent step from the subapex to the apex. Experiments employing a T2A viral peptide-containing chimera (FlbE::mRFP::T2A::FlbB::GFP) suggest that apical FlbB/FlbE interaction is inhibited in order to initiate a dynein-dependent FlbB transport to nuclei. FlbD controls the nuclear accumulation of FlbB through a cMyb domain and a C-terminal LxxLL motif. Overall, results elucidate a highly dynamic pattern of FlbB interactions, which enable timely developmental induction. Furthermore, this system establishes a reference for TF-based long-distance signaling in permanently polarized cells..

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1 8 polarity site-to-nucleus communication 1 9 2 0 2 1 2 Abstract (175 words). 1 Permanently polarized cells have developed transduction mechanisms linking 2 polarity-sites with gene regulation in the nucleus. In neurons, one mechanism is 3 based on long-distance retrograde migration of transcription factors (TFs). 4 Aspergillus nidulans FlbB is the only known fungal TF shown to migrate 5 retrogradely to nuclei from the polarized region of fungal cells known as hyphae. 6 There, FlbB controls developmental transitions by triggering the production of 7 asexual multicellular structures. FlbB dynamics in hyphae is orchestrated by 8 regulators FlbE and FlbD. At least three FlbE domains are involved in the 9 acropetal transport of FlbB, with a final MyoE/actin filament-dependent step from 1 0 the subapex to the apex. Experiments employing a T2A viral peptide-containing 1 1 chimera (FlbE::mRFP::T2A::FlbB::GFP) suggest that apical FlbB/FlbE 1 2 interaction is inhibited in order to initiate a dynein-dependent FlbB transport to 1 3 nuclei. FlbD controls the nuclear accumulation of FlbB through a cMyb domain 1 4 and a C-terminal LxxLL motif. Overall, results elucidate a highly dynamic pattern 1 5 of FlbB interactions, which enable timely developmental induction. Furthermore, 1 6 this system establishes a reference for TF-based long-distance signaling in 1 7 permanently polarized cells.