GRHL2

Cilia effects upon perturbation of GRHL2

Cilia number / % ciliated:

Decreased cilia number

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-6.91) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:

abnormal hindbrain development, abnormal abdomil wall morphology, increased startle reflex, embryonic growth retardation, abnormal pericardium morphology, syndactyly, exencephaly, abnormal placenta size, abnormal craniofacial morphology, abnormal limb morphology, abnormal neural tube morphology, preweaning lethality, complete penetrance, abnormal placenta morphology, abnormal blood vessel morphology, abnormal optic vesicle formation, abnormal forebrain development, increased freezing behavior

Mouse ciliopathy phenotype:

abnormal midbrain development, abnormal head shape, abnormal heart morphology, abnormal neural tube closure

Human ciliopathy phenotype:

autosomal dominant nonsyndromic hearing loss 28

Subcellular localization

cilia associated gene

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Cardiac & muscle development
• Transcription regulation

Function

Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2(PMID: 26527742).