BIOSIG · BIOelectrical SIGnalling in early neurodevelopment

Living tissues reliably develop into species-specific forms from noisy components, implying a distributed control system that tells cells what shape to make and when to stop. While gene regulatory networks, morphogen gradients and tissue mechanics explain much of development, they do not yet yield comprehensive, predictable control of complex 3D structures. Emerging evidence points to bioelectricity as the missing integrative layer: ion channels and gap junctions wire epithelia into electrical networks that propagate information rapidly and generate spatial patterns even in transcriptionally similar cells. BIOSIG addresses this gap in a human-relevant context by asking how bioelectrical dynamics guide early CNS morphogenesis, with a focus on neural tube folding and closing. The central hypothesis is that ion channels act as coincidence detectors, integrating mechanical, chemical and electrical cues and funneling them into canonical pathways through membrane-potential and calcium dynamics, altering cellular fate commitment, proliferation and shape change. Using human stem-cell derived neural tube organoids that recapitulate plate formation, folding and closure, BIOSIG will (i) build a 4D atlas of bioelectric activity aligned to morphology and morphogen fields; (ii) map the spatial expression of the bioelectric components (channels, connexins, transporters) and link it to live electrical states; and (iii) impose mechanical actuation and optogenetically patterned morphogen gradients, to reconstruct dorsal–ventral identity. BIOSIG will produce the first human-specific framework for bioelectric control of morphogenesis and its relation to morphogen gradients and mechanical stimulation. Beyond understanding the underlying mechanisms of diseases of developmental morphogenesis, such as neural tube defects, BIOSIG will produce valuable open resources (cell lines, code, datasets) with direct relevance to neural tube defects and, more broadly, to tissue morphogenesis.