Marco La Fortezza

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La Fortezza

First Name

Marco

ORCID

0000-0002-4485-9840

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Publications 1 - 6 of 6

Local Variation in Myxococcus xanthus Fruiting Body Development
Yuen, Lok Man; La Fortezza, Marco; Wielgoss, Sebastien; et al. (2025)
Though developmental biology has mostly focused on obligately multicellular organisms, some unicellular organisms are capable of aggregating into a multicellular structures during their life cycle. During this process, cells diﬀerentiate into multiple cell types unique to multicellular development. Myxobacteria are gram-negative bacteria capable of developing multicellular fruiting bodies upon starvation. The shape and size of fruiting bodies varies greatly between myxobacteria, both between and within species, but how this morphological diversity has evolved is poorly understood. An early study showed that morphology correlates with 16S rRNA phylogeny broadly across myxobacterial species, with more closely related species produce more similar fruiting bodies. How fruiting body morphologies might correlate with genome-based phylogenies at the intra-specific scale – the scale at which evolution plays out – has not been investigated, but may provide insights into the rate, patterns and genomic basis of morphological evolution. Here, we investigate relationships between phylogeny and fruiting body morphology in closely related isolates of the model species Myxococcus xanthus, quantifying developmental features not only of mature fruiting bodies, but as they emerge over time with time-lapse microscopy. Most strains are morphologically similar, but one monophyletic clade displays a vastly diﬀerent morphologies, with larger and fewer fruiting bodies than most isolates. While most strains have similar developmental timing, the morphologically distinct clade exhibits slower aggregation and darkening of fruiting bodies. Study of distinguishing genomic features of this clade may lead to genetic-level understanding of fine-scale, natural morphological evolution in this model species for the study of aggregative multicellularity.
Hidden paths to endless forms most wonderful: ecology latently shapes evolution of multicellular development in predatory bacteria
La Fortezza, Marco; Rendueles, Olaya; Keller, Heike; et al. (2022)
Communications Biology
Ecological causes of developmental evolution, for example from predation, remain much investigated, but the potential importance of latent phenotypes in eco-evo-devo has received little attention. Using the predatory bacterium Myxococcus xanthus, which undergoes aggregative fruiting body development upon starvation, we tested whether adaptation to distinct growth environments that do not induce development latently alters developmental phenotypes under starvation conditions that do induce development. In an evolution experiment named MyxoEE-3, growing M. xanthus populations swarmed across agar surfaces while adapting to conditions varying at factors such as surface stiffness or prey identity. Such ecological variation during growth was found to greatly impact the latent evolution of development, including fruiting body morphology, the degree of morphological trait correlation, reaction norms, degrees of developmental plasticity and stochastic diversification. For example, some prey environments promoted retention of developmental proficiency whereas others led to its systematic loss. Our results have implications for understanding evolutionary interactions among predation, development and motility in myxobacterial life cycles, and, more broadly, how ecology can profoundly shape the evolution of developmental systems latently rather than by direct selection on developmental features.
Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan
Grigolon, Giovanna; Araldi, Elisa; Erni, Reto; et al. (2022)
Nature Communications
Aging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in Caenorhabditis elegans. A compound screen identifies FDA-approved drugs able to activate human GRHL1 and promote nematodal GRH-1-dependent longevity. GRHL1 activity is regulated by post-translational lysine methylation and the phosphoinositide (PI) 3-kinase C2A. Consistently, nematodal longevity following impairment of the PI 3-kinase or insulin/IGF-1 receptor requires grh-1. In BXD mice, Grhl1 expression is positively correlated with lifespan and insulin sensitivity. In humans, GRHL1 expression positively correlates with insulin receptor signaling and also with lifespan. Fasting blood glucose levels, including in individuals with type 2 diabetes, are negatively correlated with GRHL1 expression. Thereby, GRH-1/GRHL1 is identified as a pharmacologically malleable transcription factor impacting insulin signaling and lifespan.
Group Formation: On the Evolution of Aggregative Multicellularity
La Fortezza, Marco; Schaal, Kaitlin A.; Velicer, Gregory J. (2022)
Evolutionary Cell Biology ~ The Evolution of Multicellularity
Social selection within aggregative multicellular development drives morphological evolution
La Fortezza, Marco; Velicer, Gregory J. (2021)
Proceedings of the Royal Society B: Biological Sciences
Aggregative multicellular development is a social process involving complex forms of cooperation among unicellular organisms. In some aggregative systems, development culminates in the construction of spore-packed fruiting bodies and often unfolds within genetically and behaviourally diverse conspecific cellular environments. Here, we use the bacterium Myxococcus xanthus to test whether the character of the cellular environment during aggregative development shapes its morphological evolution. We manipulated the cellular composition of Myxococcus development in an experiment in which evolving populations initiated from a single ancestor repeatedly co-developed with one of several non-evolving partners-a cooperator, three cheaters and three antagonists. Fruiting body morphology was found to diversify not only as a function of partner genotype but more broadly as a function of partner social character, with antagonistic partners selecting for greater fruiting body formation than cheaters or the cooperator. Yet even small degrees of genetic divergence between distinct cheater partners sufficed to drive treatment-level morphological divergence. Co-developmental partners also determined the magnitude and dynamics of stochastic morphological diversification and subsequent convergence. In summary, we find that even just a few genetic differences affecting developmental and social features can greatly impact morphological evolution of multicellular bodies and experimentally demonstrate that microbial warfare can promote cooperation.
Deletion of an sRNA primes development in a multicellular bacterium
La Fortezza, Marco; Verwilt, Jasper; Cossey, Sarah M.; et al. (2025)
iScience
Small non-coding RNAs (sRNAs) regulate gene expression of many biological processes. During growth, some myxobacteria produce an sRNA—Pxr—that blocks fruiting-body development, an aggregative multicellular process typically triggered by starvation. Deleting the pxr gene allows Myxococcus xanthus to develop despite nutrient availability, but Pxr binding targets and the genes regulated by Pxr remain unknown. Here, after showing that Pxr controls the temporal dynamics of development, we compare the transcriptomes of vegetative M. xanthus cells possessing vs. lacking pxr. Over half of the genes impacted by pxr deletion are linked to development, including known and previously undiscovered critical regulators. Pxr also positively regulates genes associated with general metabolic processes. Our study discovers phenotypic effects of Pxr regulation with ecological importance, identifies the suite of genes this sRNA controls during vegetative growth and reveals a previously unknown developmental regulator. These findings provide insights into the molecular mechanism controlling myxobacterial development.

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Marco La Fortezza

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