Biology subjects

Fawcett, J. P.

Publications and source records attributed to Fawcett, J. P..

3 recordsLinked to original sources

bioRxiv2026

Activity dependent regulation of Angiomotin modulates dendritic complexity in hippocampal neurons

Neuronal activity alters synaptic protein composition, which is important for maintaining dendritic complexity. Multiple signaling networks have been implicated in these processes, but how increased neuronal activity regulates their expression remains incompletely understood. The long isoform of Angiomotin, AMOT-130, is a scaffolding protein that recruits signaling proteins involved in regulating cell morphology and has been implicated in dendritic spine morphogenesis during early development. Here, we show that RNAi-mediated depletion of AMOT-130 reduces dendritic arbor complexity in neurons as early as DIV9. Elevated neuronal activity similarly decreases dendritic complexity which is accompanied by reduced AMOT-130 levels. Overexpression of AMOT-130 counteracts this morphological effect, suggesting that its activity-dependent downregulation contributes to dendritic remodelling during early development. We further, demonstrate that elevated neuronal activity promotes ubiquitin-mediated proteasomal degradation of AMOT-130, identifying a mechanism regulating its abundance in developing neurons. These findings suggest that maintaining sufficient AMOT-130 protein levels is necessary for normal dendritic arborization.

neuroscience↗

bioRxiv2026

LATS2 modulates synaptic organization and function by regulating actin dynamics

Recent work has highlighted the importance of core Hippo pathway kinases in cycling cells. Many of these kinases are also expressed in post-mitotic neurons, where they have been linked to synaptic function, and more recently a number have been shown to be dysregulated in neurodegenerative diseases such as Alzheimers disease. Despite this, little is known about the specific role or subcellular localization of the Large Tumor Suppressor kinases, LATS1 and LATS2, in postmitotic neurons. Previously, we demonstrated that LATS1 plays an important role in synapse development; however, the role of LATS2 remains poorly understood. Here, we examined the distribution and function of LATS2 and found that it is highly expressed in CA3/CA4 neurons of the hippocampus and localized throughout dendrites and dendritic spines. In contrast to LATS1, LATS2 expression remains stable throughout neuronal development. Furthermore, ectopic expression of LATS2 induces kinase-dependent structural spine defects, alters actin dynamics and reduces activity-dependent synaptic SEP-GluR1 fluorescence. Collectively, these findings reveal a unique distribution LATS2 in the hippocampus and demonstrate that LATS2 directly regulates actin dynamics and GluR1-containing AMPAR trafficking.

neuroscience↗

bioRxiv2021

Mllt11 regulates the migration and neurite outgrowth of cortical projection neurons during development

The formation of connections within the mammalian neocortex is highly regulated by both extracellular guidance mechanisms and intrinsic gene expression programs. There are generally two types of cortical projection neurons: those that project locally and interhemispherically, and those that project to sub-cerebral structures such as the thalamus, hindbrain, and spinal cord. The regulation of cortical projection morphologies is not yet fully understood at the molecular level. Here we report a role for Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in the migration and neurite outgrowth of callosal projection neurons during brain formation. We show that Mllt11 expression is exclusive to developing neurons and is enriched in the developing cortical plate, particularly during the formation of the upper or superficial cortical layers. In cultured primary cortical neurons, Mllt11 is detected in varicosities and growth cones as well as the soma. Using conditional loss-of-function and gain-of-function analysis we show that Mllt11 is a required for neuritogenesis and proper migration of upper layer cortical projection neurons. Loss of Mllt11 in the superficial cortex leads to a severe reduction in fibres crossing the corpus callosum, a progressive loss in the maintenance of upper layer projection neuron gene expression, and dysplasia of dendritic arborisation patterns. Proteomic analysis revealed that Mllt11 associates with cytoskeletal components including stabilized microtubules consistent with a role in neuronal migration and neuritogenesis. Taken together, our findings support a role for Mllt11 in promoting the formation of mature projection neuron morphologies and connectivity in the cerebral cortex.

developmental biology↗