EMBL Seminars

Abstract

Groups of cells of all kinds work together as part of multicellular behaviors ranging from collective migration to development. These behaviors are coordinated at the level of single cells, where information about other cells and the environment are encoded in intracellular signaling dynamics that then drive cellular and multicellular-level behaviors. Understanding how these complex behaviors are coordinated in nature is challenging because natural environments perturb signaling and behaviors but make it difficult to visualize behaviors. To identify how natural environments shape multicellular coordination and thus behaviors, we have designed a naturalistic soil model environment where we can visualize how cells interact with environments to affect collective outcomes. We focus on a cellular slime mold, Dictyostelium discoideum, that uses a biochemical environmental signal during starvation to coordinate aggregation into multicellular groups for continued survival. Our current findings suggest that the single-cell and population-wide signaling dynamics that coordinate development are robust in highly complex, three-dimensional environments, and that there are also other important cellular properties driving new behaviors we do not yet fully understand required for success in nature.

Abstract
Nervous systems continually integrate sensory and motor signals to coordinate behaviour, whether to enable controlled flight in an insect or a monkey plucking up a grain of food. To better understand the neural mechanisms that support movement coordination in cortex, my lab studies the neural representation of body posture in freely moving rats. To this end, we developed methods to integrate 3D motion capture with high-density neural recordings to visualize neural spiking in relation to 3D pose dynamics, which revealed dense coding of head and back kinematics in posterior parietal cortex (PPC) and secondary motor cortices. Follow-up work showed that posture and movement signals were widespread among primary sensory and motor cortices, including auditory, visual and somatosensory areas. This ubiquity of kinematic tuning prompted us to expand our framework to include head-mounted high speed (200 FPS) tracking of the whiskers and eyes, to ask how sensory (vibrissal) deployment integrates with head kinematics and whole-body movement. This approach was combined with Neuropixels recordings spanning the PPC and neighboring S1 barrel fields. Ongoing work indicates that single neurons in S1 and the PPC alike conjunctively encode whisker posture and head kinematics, and that this can be further gated by locomotion. Our observations indicate that whisker deployment and head movements are fully interwoven during naturalistic behavior, which is reflected in cortical coding in both primary and associative areas

Abstract
Drastic epigenetic reprogramming occurs during mammalian early embryogenesis. Deciphering the molecular events underlying these processes is crucial for understanding how epigenetic information is transmitted between generations and how life really begins. Probing these questions was previously hindered by the scarce experimental materials that are available in early development. By developing a set of ultra-sensitive chromatin analysis technologies, we investigated chromatin reprogramming during early mouse development for chromatin accessibility, histone modifications, and 3D architecture. These studies unveiled highly dynamic and non-canonical chromatin regulation during maternal-to-zygotic transition and zygotic genome activation (ZGA). However, how ZGA is kickstarted and how the early development program is progressively driven by transcription factors (TFs) remain enigmatic. Recently, we identified key TFs that act at the onset of ZGA, and those that connect ZGA to the first cell fate commitment. In this talk, I will discuss how TFs and epigenetic factors cooperatively establish embryonic program and restore the embryonic epigenomes when the life begins. 

Abstract
Memory formation relies on a bidirectional interplay between synaptic plasticity and nucleus-templated transcriptional programs, but how precisely this interplay is orchestrated by epigenetic mechanisms remains to a large extent unknown. In this talk, I will showcase our recent efforts to better understand this aspect from two angles. First, we have found that chromatin plasticity in the mouse brain is a key determinant for memory allocation, the process by which neurons become recruited into the memory trace: When we increased chromatin plasticity by enzymatic overexpression of histone acetyl transferases (HATs), neurons with elevated histone acetylation were preferentially recruited into the encoding ensemble and memory retention was enhanced, while optogenetic silencing of the epigenetically altered neurons prevented memory expression. Second, we have found that after learning, the epigenetic make-up of a single locus in the encoding ensemble is necessary and sufficient to bidirectionally alter memory performance across different phases of memory consolidation. Together, these findings stipulate that before and after memory encoding, epigenetic mechanisms play a pivotal role as molecular memory aids.