Wnt Signaling Drives Correlated Changes in Facial Morphology and Brain Shape

Abstract

Canonical Wnt signaling plays multiple roles critical to normal craniofacial development while its dysregulation is known to be involved in structural birth defects of the face. However, when and how Wnt signaling influences phenotypic variation, including those associated with disease, remains unclear. One potential mechanism is via Wnt signaling’s role in the patterning of an early facial signaling center, the frontonasal ectodermal zone (FEZ), and its subsequent regulation of early facial morphogenesis. For example, Wnt signaling may directly alter the shape and/or magnitude of expression of the sonic hedgehog (SHH) domain in the FEZ. To test this idea, we used a replication-competent avian sarcoma retrovirus (RCAS) encoding Wnt3a to modulate its expression in the facial mesenchyme. We then quantified and compared ontogenetic changes in treated to untreated embryos in the three-dimensional (3D) shape of both the SHH expression domain of the FEZ, and the morphology of the facial primordia and brain using iodine-contrast microcomputed tomography imaging and 3D geometric morphometrics (3DGM). We found that increased Wnt3a expression in early stages of head development produces correlated variation in shape between both structural and signaling levels of analysis. In addition, altered Wnt3a activation disrupted the integration between the forebrain and other neural tube derivatives. These results show that activation of Wnt signaling influences facial shape through its impact on the forebrain and SHH expression in the FEZ, and highlights the close relationship between morphogenesis of the forebrain and midface.

Thirty years of geometric morphometrics: Achievements, challenges, and the ongoing quest for biological meaningfulness

“…Since then, geometric morphometrics has been continually refined and has found countless applications in biological, anthropological, paleontological, medical, psychological, archeological, and industrial fields (for reviews see, e.g., Adams & Otárola‐Castillo, 2013; Bookstein, 2018; Cardini, 2020; Elewa, 2010; Halazonetis, 2004; Klingenberg, 2010; Lawing & Polly, 2010; MacLeod, 2018; Mitteroecker, 2020; Mitteroecker & Gunz, 2009; Schaefer et al, 2009; Slice, 2005; Wiley et al, 2005; Zelditch et al, 2012). The geometric morphometric toolkit has also been connected to other methodologies, including biomechanics (e.g., O'Higgins et al, 2019; Parr et al, 2012; Polly et al, 2016; Weber et al, 2011), systematics and phylogenetics (e.g., Adams, 2014; Klingenberg & Gidaszewski, 2010; Monteiro, 2013; Rohlf, 2002), image analysis (e.g., Mayer et al, 2014, 2017), quantitative genetics (e.g., Adams, 2011; Baab, 2018; Klingenberg & Leamy, 2001; Martínez‐Abadías et al, 2009; Pavličev et al, 2016; Schroeder & von Cramon‐Taubadel, 2017), genetic mapping (e.g., Klingenberg et al, 2001; Mitteroecker et al, 2016; Pallares et al, 2015; Varón‐González et al, 2019), evolutionary psychology and brain imaging (e.g., Walla et al, 2020; Windhager et al, 2012, 2018) as well as molecular and developmental biology (e.g., Arif et al, 2013; Buchberger et al, 2021; Hallgrimsson et al, 2015; Marchini et al, 2021; Martínez‐Abadías et al, 2018). Recent implementations of geometric morphometric methods into R and Mathematica facilitated analyses (Adams & Otárola‐Castillo, 2013; Dryden, 2021; Dryden & Mardia, 2016; Polly, 2017; Schlager, 2017).…”

High-quality chromosome-level genome assembly of the melon-headed whale (<i>Peponocephala electra</i>)

“…Nevertheless, we observed an expansion for genes enriched in several GO terms, including “wnt signaling pathway”, “head development”, and “neuron projection morphogenesis” ( P <0.01) using Metascape (Supplementary Figure S5). We speculate that these genes may play a role in the development of the pointed, melon-shaped head in P. electra ( Marchini et al, 2021 ), but await the availability of additional chromosome-level cetacean genomes .…”

MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses

“…Because developmental 13 homology was not a consideration for the adults, we landmarked the adult atlas in MINC using built-in display tools, again ensuring sparse and dense landmark coverage. Shared developmental pathways lead to correlated morphological variation, or morphological integration [51][52][53][54][55][56][57] . To enable analyses of integration, we added landmark configurations to segmented surfaces of the adult skull atlas.…”