SummaryNeural induction in vertebrates generates a CNS that extends the rostral-caudal length of the body. The prevailing view is that neural cells are initially induced with anterior (forebrain) identity; caudalizing signals then convert a proportion to posterior fates (spinal cord). To test this model, we used chromatin accessibility to define how cells adopt region-specific neural fates. Together with genetic and biochemical perturbations, this identified a developmental time window in which genome-wide chromatin-remodeling events preconfigure epiblast cells for neural induction. Contrary to the established model, this revealed that cells commit to a regional identity before acquiring neural identity. This “primary regionalization” allocates cells to anterior or posterior regions of the nervous system, explaining how cranial and spinal neurons are generated at appropriate axial positions. These findings prompt a revision to models of neural induction and support the proposed dual evolutionary origin of the vertebrate CNS.
How left-right patterning drives asymmetric morphogenesis is unclear. Here, we have quantified shape changes during mouse heart looping, from 3D reconstructions by HREM. In combination with cell labelling and computer simulations, we propose a novel model of heart looping. Buckling, when the cardiac tube grows between fixed poles, is modulated by the progressive breakdown of the dorsal mesocardium. We have identified sequential left-right asymmetries at the poles, which bias the buckling in opposite directions, thus leading to a helical shape. Our predictive model is useful to explore the parameter space generating shape variations. The role of the dorsal mesocardium was validated in Shh-/- mutants, which recapitulate heart shape changes expected from a persistent dorsal mesocardium. Our computer and quantitative tools provide novel insight into the mechanism of heart looping and the contribution of different factors, beyond the simple description of looping direction. This is relevant to congenital heart defects.
SummaryUsing high-resolution live imaging in zebrafish, we show that presumptive eye cells acquire apicobasal polarity and adopt neuroepithelial character prior to other regions of the neural plate. Neuroepithelial organization is first apparent at the margin of the eye field, whereas cells at its core have mesenchymal morphology. These core cells subsequently intercalate between the marginal cells contributing to the bilateral expansion of the optic vesicles. During later evagination, optic vesicle cells shorten, drawing their apical surfaces laterally relative to the basal lamina, resulting in further laterally directed evagination. The early neuroepithelial organization of the eye field requires Laminin1, and ectopic Laminin1 can redirect the apicobasal orientation of eye field cells. Furthermore, disrupting cell polarity through combined abrogation of the polarity protein Pard6γb and Laminin1 severely compromises optic vesicle evagination. Our studies elucidate the cellular events underlying early eye morphogenesis and provide a framework for understanding epithelialization and complex tissue formation.
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