Three-dimensional cellular dynamics and mandibular morphogenesis.

Introduction: Shaping the face requires the coordination of molecular and cellular behaviours that direct tissue-wide dynamics of development. A limited, well-conserved suite of cell behaviours, including cell proliferation, facilitate cellular contributions to morphogenesis, which are in turn regulated by the tissues they comprise. However, the role of cell behaviours in early facial tissues remains poorly characterized, despite underlying both healthy and syndromic facial development. Methods: By integrating light-sheet fluorescence microscopy, shape quantification, and semi-automated image segmentation, we resolve individual cell behaviours and their relationships to morphogenesis across large tissue domains in the developing mandible. We focus on cell proliferation and mitotic orientation, but also analyze cellular morphology and cell-tissue relationships via positional orientation. Results: Here, we describe three-dimensional patterns of cell behaviours in the context of mandibular morphogenesis. We show that several cell behaviours are mediolaterally patterned in tandem at E10.5, a critical point in development. These patterns align with preceding growth, and occur several days before the onset of cell fate commitment. Discussion: These observations reflect the reciprocal interplay between molecular, cellular, and tissue-level processes, highlighting how subtle differences in cell behaviours are connected to complex growth patterns even in largely homogeneous tissues.