Biology subjects

Mallamaci, A.

Publications and source records attributed to Mallamaci, A..

4 recordsLinked to original sources

bioRxiv2026

Foxg1 promotes neuron allocation to engrams and facilitates fear memorization

In addition to orchestrate telencephalic development, the transcription factor Foxg1 is involved in mutual positive feedback with neuronal activity. Based on that, we hypothesized an involvement of it in learning and engram dynamics. We observed that its sparse and mild neuronal upregulation improved learning abilities as evaluated by a CFC assay. This effect was specifically pronounced upon early memory retrieval and disappeared when Foxg1-GOF neurons were silenced by a Gi DREADD effector. A prevailing positive relationship was detectable between Foxg1 expression level and the probability of a neuron getting recruited into training and recall engrams, in structures involved in both short- and long-term memory formation. Moreover, Foxg1 upregulation elicited a generalized shrinkage of engrams and increased the fraction of late recall engram cells already active at the time of training. Together, these findings establish Foxg1 as a key effector linking neuronal excitability to engram allocation and memory recall.

neuroscience↗

bioRxiv2024

Foxg1 and companions: not only transcription factors

Here, moving from our most recent results on Foxg1 biology, we firstly summarize available information about a few, special pleiotropic effectors of neurodevelopmental interest, involved in control of both transcription and post-transcriptional steps of gene expression. Next, upon further scanning of literature, we report evidence that, not strictly limited to neurodevelopmental processes, such functional pleiotropy also applies to other transcription factors, involved in physiology and homeostasis. Besides, by systematic mining of a major public protein-protein interaction database, we collect robust evidence that an involvement of "canonical" transcription factors in post-transcriptional control of gene expression may be a pervasive phenomenon, characterizing hundreds of effectors. Finally, we discuss the biological meaning of these findings and propose three evolutionary mechanisms that may have conspired to such unexpected scenario.

molecular biology↗

bioRxiv2023

Foxg1 bimodally tunes L1-mRNA and -DNA dynamics in the developing murine neocortex

Foxg1 masters telencephalic development via a pleiotropic control of its articulation. L1 is a large retrotransposon family expressed within CNS and suggested to contribute to its genomic plasticity. Foxg1 represses gene transcription, and L1 elements share putative Foxg1 binding motifs, suggesting the former might limit telencephalic expression (and activity) of the latter. We tested such prediction, in vivo as well as in engineered primary neural cultures, by loss- and gain-of-function approaches. We showed that Foxg1-dependent, transcriptional L1 repression specifically occurs in neopallial neuronogenic progenitors and post-mitotic neurons, where it is supported by specific changes in the L1 epigenetic landscape. Unexpectedly, we also found that Foxg1 physically interacts with L1-mRNA and positively impacts on neonatal neopallium L1-DNA content, antagonizing the retrotranscription-suppressing activity exerted by Mov10 and Ddx39a helicases. To our knowledge, Foxg1 is the first CNS patterning gene acting as a bimodal retrotransposon modulator, limiting and promoting L1 transcription and amplification, respectively, within a specific domain of the developing mouse brain.

developmental biology↗

bioRxiv2022

Foxg1 regulates translation of neocortical neuronal genes, including the main NMDA receptor subunit gene, Grin1.

Mainly known as a transcription factor patterning the rostral brain and governing its histogenesis, Foxg1 has been also detected outside the nucleus, however biological meaning of that has been only partially clarified. Here, moving from Foxg1 expression in cytoplasm of neocortical neurons, we investigated its implication in translational control. We documented an impact of Foxg1 on ribosomal recruitment of Grin1-mRNA, encoding for the main subunit of NMDA receptor. Next, we showed that Foxg1 increases Grin1 protein level by enhancing translation of its mRNA, while not increasing its stability. Such enhancement was associated to augmented translational initiation and, possibly, polypeptide elongation. Molecular mechanisms at the basis of this activity included Foxg1 interaction with Eif4e and Eef1d as well as with Grin1-mRNA. Besides, we found that, within murine neocortical cultures, Grin1 de novo synthesis undergoes a prominent and reversible, homeostatic regulation and Foxg1 is instrumental to that. Finally, through TRAP-seq, we discovered that Foxg1 is implicated in the translation of hundreds of neuronal genes at the level of ribosome engagement and progression. All that points to Foxg1 as a key effector, crucial to multi-scale temporal tuning of neocortical pyramid activity, an issue with profound physiological and neuropathological implications.

molecular biology↗