Biology subjects

Panagiotakos, G.

Publications and source records attributed to Panagiotakos, G..

3 recordsLinked to original sources

bioRxiv2025

Cell Cycle Arrest of a "Zippering" Epithelial Cell Cluster Shapes the Face and is Disrupted in Craniofacial Disorders

Facial features identify individuals, but the mechanisms shaping the human face remain elusive. Orofacial clefting (OFC), the most common craniofacial abnormality, results from failed fusion of the facial prominences that is in part caused by persistence of the cephalic epithelium. Here we uncover the identity, behaviors, and molecular blueprints of a novel craniofacial epithelial population, the Zippering Lambda (ZL), which mediates prominence fusion and is characterized by cell cycle arrest in mouse and human embryos. Remarkably, cell cycle is unleashed in the ZL of Pbx1/2 and p63 mutant mice with OFC. Intersection of ZL-enriched genes with human OFC whole-genome sequencing datasets identifies ZFHX3 variants in affected individuals and cephalic epithelial Zfhx3 deletion causes murine OFC. ZFHX3 and PBX1 genetically interact and synergistically regulate cell cycle inhibitor genes within a complex in embryonic faces. Collectively, we deconstruct new mechanisms that pattern the face, connecting cell cycle arrest to developmental tissue fusion.

developmental biology↗

bioRxiv2020

The npBAF to nBAF Chromatin Switch Regulates Cell Cycle Exit in the Developing Mammalian Cortex

Nervous system development is orchestrated by tightly-regulated progenitor cell divisions, followed by differentiation at precise but varying times across different regions. As progenitors exit the cell cycle, they initiate a subunit switch of the mSWI/SNF or npBAF complex to generate neuron-specific nBAF complexes. These chromatin regulatory complexes play dosage-sensitive roles in neural development and are frequently mutated in neurodevelopmental disorders. Here we manipulated the timing of BAF subunit exchange in the developing mouse brain and find that deletion of the npBAF subunit BAF53a blocks progenitor proliferation, leading to impaired neurogenesis. We show that npBAF complexes regulate cell cycle progression by antagonizing Polycomb complexes to promote chromatin accessibility at cell cycle and NPC identity genes. Replacement of the actin-related protein, Actl6a (BAF53a) by the neuron-specific actin-related protein, Actl6b (BAF53b), but not other regulators of proliferation, rescues progenitors by promoting neuronal differentiation. We propose that the function of the npBAF to nBAF chromatin switch is to control progenitor cell cycle exit and promote synchronous neural differentiation.

developmental biology↗

bioRxiv2017

Two-stage adaptation of inhibition mediates predictive sensitization in the retina

A critical function of the nervous system is the prediction of future sensory input. One such predictive computation is retinal sensitization, a form of short-term plasticity seen in multiple species that elevates local sensitivity following strong local stimulation. Here we perform a causal circuit analysis of retinal sensitization using simultaneous intracellular and multielectrode recording in the salamander. We show, using direct current injection into inhibitory sustained amacrine cells that a decrease in amacrine transmission is necessary, sufficient and occurs at the right time and manner to cause sensitization in ganglion cells. Because of neural dynamics and nonlinear pathways, a computational model is essential to explain how a change in steady inhibitory transmission causes sensitization. Whereas adaptation of excitation removes an expected result in order to transmit novelty, adaptation of inhibition provides a general mechanism to enhance the sensitivity to the sensory feature conveyed by an inhibitory pathway, creating a prediction of future input.

neuroscience↗