Abstract
ABSTRACTThe folding of epithelial tissues is crucial for development of three-dimensional structure and function. Understanding this process can assist in determining the etiology of developmental disease and engineering of tissues for the future of regenerative medicine. Folding of epithelial tissues towards the apical surface has long been studied, but the molecular mechanisms that mediate epithelial folding towards the basal surface are just emerging. Here, we utilize zebrafish neuroepithelium to identify mechanisms that mediate basal tissue folding to form the highly conserved embryonic midbrain-hindbrain boundary. Live imaging revealed Wnt5b as a mediator of anisotropic epithelial cell shape, both apically and basally. In addition, we uncovered a Wnt5b-mediated mechanism for specific regulation of basal anisotropic cell shape that is microtubule dependent and likely to involve JNK signaling. We propose a model in which a single morphogen can differentially regulate apical versus basal cell shape during tissue morphogenesis.
Highlights
The folding of epithelial tissues is essential for the generation of complex three-dimensional organ structures during morphogenesis
We found a significant decrease in β-tubulin levels in the basal domain of midbrain-hindbrain boundary constriction (MHBC) cells in wnt5b morphants compared with controls (Fig. 3F-H), demonstrating that Wnt5b is essential for the basal microtubule population at the MHBC
Differences in anisotropic cell shape were not observed in cells outside the MHBC with Jun N-terminal kinase (JNK) inhibition (Fig. S8). These results indicate that JNK is required for midbrainhindbrain boundary (MHB) basal tissue folding through specific modulation of MHBC basal anisotropic cell shape
Summary
The folding of epithelial tissues is essential for the generation of complex three-dimensional organ structures during morphogenesis. The pseudostratified neuroepithelium that gives rise to the central nervous system has gained significant attention for its complex structure and the substantial shape changes that occur during its development (Norden, 2017). Apical constriction mediates epithelial folding towards the apical surface during neurulation, and many of the molecular mechanisms that mediate apical constriction have been elucidated in both vertebrate and invertebrate systems (Hunter and Fernandez-Gonzalez, 2017; Martin and Goldstein, 2014). Later in embryonic brain morphogenesis, the neuroepithelium folds towards the basal surface to generate the highly conserved midbrainhindbrain boundary (MHB). A significant gap remains in our understanding of the molecular mechanisms that mediate basal tissue folding
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