NF1

Cilia effects upon perturbation of NF1

Ciliogenesis screen results (5 screens)

• Kim2016: No effect
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.04) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-1.27) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: Hyper-ciliogenesis (robust z=2.03, ciliated=53.2%) PMID:26595381
• Kim et al. 2010 (siRNA) [siRNA]: Longer Cilia (Area per Cilia z=5.29) PMID:20393562

Phenotypes

Mouse phenotype:

preweaning lethality, complete penetrance, inflammation

Subcellular localization

cilia associated gene, microtubules, nucleus, ribosome

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Neurogenesis & migration
• Protein processing & maturation
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)
• Cardiac & muscle development

Function

Neurofibromin, the product of the Neurofibromatosis-1 gene (NF1), a major Ras GTPase activating protein (RasGAP) in neural cells, controls also the critical function of chromosome congression in astrocytic cellular contexts. NLS-neurofibromin knockdown led to increased density of cytosolic MTs but loss of MT intersections, a stral spindles featuring large hollows and abnormal chromosome positioning, and fi lly abnormal chromosome segregation and increased micronuclei frequency. Differential neurofibromin isoform colocalization with γ-tubulin on mitotic centrosomes( 33114250).