Zebrafishcrocc2mutants exhibit divergent craniofacial shape, misregulated variability, and aberrant cartilage morphogenesis

Abstract

Background Phenotypic variation is of paramount importance in development, evolution, and human health; however, the molecular mechanisms that influence organ shape and shape variability are not well understood. During craniofacial development, the behavior of skeletal precursors is regulated by both biochemical and environmental inputs, and the primary cilia play critical roles in transducing both types of signals. Here, we examine a gene that encodes a key constituent of the ciliary rootlets, crocc2, and its role in cartilage morphogenesis in larval zebrafish. Results Geometric morphometric analysis of crocc2 mutants revealed altered craniofacial shapes and expanded variation. At the cellular level, we observed altered chondrocyte shapes and planar cell polarity across multiple stages in crocc2 mutants. Notably, cellular defects were specific to areas that experience direct mechanical input. Cartilage cell number, apoptosis, and bone patterning were not affected in crocc2 mutants. Conclusions Whereas “regulatory” genes are widely implicated in patterning the craniofacial skeleton, genes that encode “structural” aspects of the cell are increasingly implicated in shaping the face. Our results add crocc2 to this list, and demonstrate that it affects craniofacial geometry and canalizes phenotypic variation. We propose that it does so via mechanosensing, possibly through the ciliary rootlet. If true, this would implicate a new organelle in skeletal development and evolution.

Foraging-induced craniofacial plasticity is associated with an early, robust and dynamic transcriptional response

“…We then ran a generalized Procrustes analysis (GPA) on landmark data. From whole shape landmark data, we quantified shape change trajectories between environments (shape ∼ species × treatment, ∼ centroid size), or over time (shape ∼ species × time, ∼centroid size) using the trajectory.analysis function in Geomorph v3.0 [ 31 ] following [ 32 ]. This function uses ANOVA to evaluate the trajectories, and calculates the differences in trajectory path and magnitude.…”