SPECC1L

Cilia effects upon perturbation of SPECC1L

Cilia number / % ciliated:

No effect

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-5.14) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:

hyperactivity; decreased circulating calcium level

Ciliopathy associations

• Frontonasal Dysplasia

Subcellular localization

actin filaments, cilia associated gene, cytoskeleton

Functional category

• Metabolism; Signaling (Hedgehog, GPCRs, ion channels); Cilia???cytoskeleton/adhesion links

Function

We have shown that increased F-actin upon SPECC1L deficiency results in shortened cilia and increased Hh signaling in the palate at E13.5 (Hufft-Martinez et al., 2025). Thus, we expected cilia length and Hh signaling in the cranial mesenchyme to be perturbed. Indeed, cilia lengths were significantly decreased in Specc1lΔCNCC cranial mesenchyme at E13.5 (Fig.4A,B). Consistent with the ciliary defect, expression of GLI1, a downstream activator of hedgehog signaling, was increased in the Specc1lΔCNCC cranial mesenchyme (Fig.4C,D). Altered Hh signaling in ciliary mutants is known to affect canonical WNT signaling (Kurosaka et al., 2014). To this end we assessed expression of functionally active β-catenin, which was significantly decreased in Specc1lΔCNCC cranial mesenchyme (Fig.4E,F), consistent with the observed decrease in cell proliferation. (41332626).