Biology subjects

Rosenthal, S.

Publications and source records attributed to Rosenthal, S..

2 recordsLinked to original sources

bioRxiv2025

Role of the obligate STRIPAK complex component Mob4 in zebrafish vascular development and stability

The STRiatin Interacting Phosphatases and Kinases (STRIPAK) complex is a conserved multiprotein module with functions in cell proliferation, cell growth, and cancer. Primarily examined through proteomic and in vitro studies, there is a relative lack of insight into the in vivo function of the STRIPAK complex during development. Motivated by the prominent interaction of STRIPAK and the CCM3 adapter protein, which is associated with the vascular disease cerebral cavernous malformation (CCM), we sought to examine the role of the conserved STRIPAK component Mob4 in early zebrafish vascular development. We use proximity-dependent biotinylation (BioID) coupled with mass spectrometry to show that Mob4 is a component of the STRIPAK complex in zebrafish. Loss of mob4 leads to pronounced cardiovascular and neuronal defects, including a leaky cerebral vasculature, hypersprouting of venous endothelial cells and poor neuronal branching. Conditional transgenic models further demonstrate a continuous and broad requirement for Mob4 in development. Taken together, these results suggest a key role for STRIPAK function in vascular development and stability, replicating hallmarks of CCM.

developmental biology↗

bioRxiv2019

Increased expression of schizophrenia-associated gene C4 leads to hypoconnectivity of prefrontal cortex and reduced social interaction

Schizophrenia is a severe mental disorder with an unclear pathophysiology. Increased expression of the immune gene C4 has been linked to a greater risk of developing schizophrenia; however, it is unknown whether C4 plays a causative role in this brain disorder. Using confocal imaging and whole-cell electrophysiology, we demonstrate that overexpression of C4 in mouse prefrontal cortex neurons leads to perturbations in dendritic spine development and hypoconnectivity, which mirror neuropathologies found in schizophrenia. We find evidence that microglia-neuron interactions and microglia-mediated synaptic engulfment are enhanced with increased expression of C4. We also show that C4-dependent circuit dysfunction in the frontal cortex leads to decreased social interactions in juvenile mice. These results demonstrate that increased expression of the schizophrenia-associated gene C4 causes aberrant circuit wiring in the developing prefrontal cortex and leads to deficits in early social behavior, suggesting that altered C4 expression contributes directly to schizophrenia pathogenesis.

neuroscience↗