Genes regulating spindle orientation and mutated in diseases
| Gene name – species | Cellular function | Associated disease | Molecular characteristics | ||
| Vertebrate | Fly | Worm | |||
| lis1 | lis1 | lis-1 | Dynein-based movement, nucleokinesis (vertebrate, fly, worm), spindle orientation (vertebrate, fly), chromosome alignment (vertebrate), centrosome separation (fly, worm) spindle positioning (worm) (Swan et al., 1999; Dawe et al., 2001; Cockell et al., 2004; Siller and Doe, 2008; Wynshaw-Boris et al., 2010) | Lissencephaly (Reiner et al., 1993; Lo Nigro et al., 1997) | Coiled-coil domain, WD40 repeats |
| dcx | CG17528a | zyg-8 | Microtubule polymerization (vertebrate, worm), spindle orientation (vertebrate), spindle positioning (worm) (Gönczy et al., 2001; Pramparo et al., 2010; Wynshaw-Boris et al., 2010) | Lissencephaly (des Portes et al., 1998; Gleeson et al., 1998) | Doublecortin domain, kinase domain |
| nde1 | nudE | nud-2 | Centrosome duplication and maturation, chromosome alignment, spindle orientation, nucleokinesis (vertebrate), kinetochore function, chromosome congression, centrosome behavior (fly), nuclear migration (worm) (Wainman et al., 2009; Fridolfsson et al., 2010; Chansard et al., 2011) | Microlissencephaly (Alkuraya et al., 2011; Bakircioglu et al., 2011) | Coiled-coil domain |
| Gαi1, Gαi2, Gαi3 | Gαi1 | goa-1, gpa-16 | Spindle orientation (vertebrate, fly), ACD (fly, worm), spindle positioning, chromosome segregation (worm) (Srinivasan et al., 2003; Morin and Bellaïche, 2011) | – | GTPase subunit of heterotrimeric G proteins |
| numa | mud | lin-5 | ACD, chromosome segregation (vertebrate, fly, worm), spindle orientation, spindle pole integrity (vertebrate, fly), spindle positioning, cytokinesis (worm) (Lorson et al., 2000; Radulescu and Cleveland, 2010; Capalbo et al., 2011; Morin and Bellaïche, 2011; Kolano et al., 2012) | Leukemia (Wells et al., 1997) | Coiled-coil domain |
| pins/lgn/gpsm2/ags3 | pins | gpr-1, gpr-2 | ACD (vertebrate, fly, worm), spindle orientation (vertebrate, fly), chromosome segregation (vertebrate, worm), spindle positioning (worm) (Du et al., 2001; Srinivasan et al., 2003; Morin and Bellaïche, 2011) | Non-syndromic deafness (Walsh et al., 2010), brain malformations and deafness in Chudley-McCullough syndrome (Doherty et al., 2012) | GoLoco motif, tetratricopeptide (TPR) domains |
| insc | insc | – | Spindle orientation (vertebrate, fly), asymmetric cell division (fly) (Morin and Bellaïche, 2011) | – | Armadillo repeats |
| htt | htt | F21G4.6a | Neuronal transport, spindle orientation (vertebrate, fly) (Gunawardena et al., 2003; Godin and Humbert, 2011) | The Huntington’s Disease Collaborative Research Group (1993) | Polyglutamine tract, polyproline sequence, HEAT repeats |
| magoh | mago | mag-1 | RNA processing (vertebrate, fly worm), RNA localization (vertebrate, fly), spindle orientation and integrity, genomic stability (vertebrate), cytoskeleton organization (fly) (Li et al., 2000; Kataoka et al., 2001; Palacios, 2002; Le Hir and Andersen, 2008; Silver et al., 2010) | – | Mago nashi domain |
| apc | apc1, apc2 | apr-1 | Wnt signaling, ACD, microtubule stability (vertebrate, fly, worm), spindle orientation (vertebrate, fly), chromosome segregation, tumor suppressor (vertebrate) (Yamashita et al., 2003; Mizumoto and Sawa, 2007; McCartney and Näthke, 2008; Bahmanyar et al., 2009) | Familial adenomatous polyposis (FAP), gastrointestinal tumors (Minde et al., 2011) | Armadillo repeats, oligomerization domain, CRM1, β-catenin, microtubule-binding domains, |
| vegf | pvf1, pvf2, pvf3 | pvf-1 | Cell migration (vertebrate, fly), growth factor, oncogene, spindle orientation, angiogenesis (vertebrate) (Duchek et al., 2001; Tarsitano et al., 2006; Beck et al., 2011; Sitohy et al., 2012) | Epithelia skin cancer (Beck et al., 2011) | PDGF domain |
| vhl | vhl | vhl-1 | HIF1α regulation (vertebrate, fly, worm), microtubule stability, endocytosis, cell migration (vertebrate, fly), tumor suppressor, spindle orientation, genome integrity (vertebrate) (Thoma et al., 2009; Hsu, 2012) | Renal cell carcinoma (Kaelin, 2008) | Cullin E3 ubiquitin ligase |
| pten | pten | daf-18 | PI3K signaling (vertebrate, fly, worm), tumor suppressor, spindle orientation, genome integrity, cell growth (vertebrate), cell growth, actin cytoskeleton organization, (fly) (Ogg and Ruvkun, 1998; Stocker and Hafen, 2000; von Stein et al., 2005; Toyoshima et al., 2007; Hollander et al., 2011) | PTEN hamartoma tumor syndromes (PHTS) (Hollander et al., 2011) | Protein and lipid phosphatase |
| mcph1/microcephalin/brit1 | mcph1 | – | DNA damage response, centrosome integrity, chromosome segregation (vertebrate, fly), spindle orientation (vertebrate) (Thornton and Woods, 2009; Gruber et al., 2011) | Microcephaly (Jackson et al., 2002) | BRCA1 C-terminal (BRCT) domains |
| mcph2/wdr62 | – | – | Centrosome integrity, spindle orientation, chromosome alignment (vertebrate) (Bogoyevitch et al., 2012) | Microcephaly, lissencephaly, schizencephaly (Bilgüvar et al., 2010; Nicholas et al., 2010; Yu et al., 2010) | WD40 repeats |
| mcph3/cdk5rap2/cep215 | cnn | – | Centrosome assembly, spindle orientation, chromosome segregation (vertebrate, fly), DNA damage response (vertebrate) (Siller and Doe, 2008; Megraw et al., 2011) | Microcephaly (Bond et al., 2005) | Coiled-coil domains, centrosomin motives (CM) 1 and 2 |
| mcph4/cep152 | asl | – | Centriole formation and duplication (vertebrate, fly), genome integrity (vertebrate) (Kalay et al., 2011; Brito et al., 2012) | Microcephaly (Guernsey et al., 2010), Seckel syndrome (Kalay et al., 2011) | Coiled-coil domains |
| mcph5/aspm/calmbp1 | asp | aspm-1 | Spindle assembly, spindle orientation, cytokinesis (vertebrate, fly), the integrity of spindle poles and the central spindle (fly), meiotic spindle orientation (worm) (Varmark, 2004; van der Voet et al., 2009; Higgins et al., 2010) | Microcephaly (Bond et al., 2002), tumorigenesis (Lin et al., 2008) | Calponin homology (CH) domains, IQ-repeat motifs |
| mcph6/cenpj/cpap | sas4 | sas-4 | Centriole duplication (vertebrate, fly, worm), spindle orientation (vertebrate), ACD (fly) (Leidel and Gönczy, 2005; Basto et al., 2006; Kitagawa et al., 2011; Brito et al., 2012) | Microcephaly (Bond et al., 2005), Seckel syndrome (Al-Dosari et al., 2010) | Coiled-coil motives, PN2-3 domain, T-complex protein 10 (TCP) domain |
| mcph7/stil/sil | ana2 | sas-5 | Centriole duplication (vertebrate, fly, worm), spindle orientation (vertebrate, fly), ACD (fly) (Leidel and Gönczy, 2005; Wang et al., 2011; Brito et al., 2012) | Microcephaly (Kumar et al., 2009), leukemia (Aplan et al., 1991) | Coiled-coil domain, STIL/ANA2 (STAN) motif |
| cep63 | – | – | Spindle assembly, mitotic entry, genome maintenance, centrosome duplication (vertebrate) (Smith et al., 2009; Löffler et al., 2011) | Microcephaly (Sir et al., 2011) | Coiled-coil domains |
| Gene name – species | Cellular function | Associated disease | Molecular characteristics | ||
| Vertebrate | Fly | Worm | |||
| lis1 | lis1 | lis-1 | Dynein-based movement, nucleokinesis (vertebrate, fly, worm), spindle orientation (vertebrate, fly), chromosome alignment (vertebrate), centrosome separation (fly, worm) spindle positioning (worm) (Swan et al., 1999; Dawe et al., 2001; Cockell et al., 2004; Siller and Doe, 2008; Wynshaw-Boris et al., 2010) | Lissencephaly (Reiner et al., 1993; Lo Nigro et al., 1997) | Coiled-coil domain, WD40 repeats |
| dcx | CG17528a | zyg-8 | Microtubule polymerization (vertebrate, worm), spindle orientation (vertebrate), spindle positioning (worm) (Gönczy et al., 2001; Pramparo et al., 2010; Wynshaw-Boris et al., 2010) | Lissencephaly (des Portes et al., 1998; Gleeson et al., 1998) | Doublecortin domain, kinase domain |
| nde1 | nudE | nud-2 | Centrosome duplication and maturation, chromosome alignment, spindle orientation, nucleokinesis (vertebrate), kinetochore function, chromosome congression, centrosome behavior (fly), nuclear migration (worm) (Wainman et al., 2009; Fridolfsson et al., 2010; Chansard et al., 2011) | Microlissencephaly (Alkuraya et al., 2011; Bakircioglu et al., 2011) | Coiled-coil domain |
| Gαi1, Gαi2, Gαi3 | Gαi1 | goa-1, gpa-16 | Spindle orientation (vertebrate, fly), ACD (fly, worm), spindle positioning, chromosome segregation (worm) (Srinivasan et al., 2003; Morin and Bellaïche, 2011) | – | GTPase subunit of heterotrimeric G proteins |
| numa | mud | lin-5 | ACD, chromosome segregation (vertebrate, fly, worm), spindle orientation, spindle pole integrity (vertebrate, fly), spindle positioning, cytokinesis (worm) (Lorson et al., 2000; Radulescu and Cleveland, 2010; Capalbo et al., 2011; Morin and Bellaïche, 2011; Kolano et al., 2012) | Leukemia (Wells et al., 1997) | Coiled-coil domain |
| pins/lgn/gpsm2/ags3 | pins | gpr-1, gpr-2 | ACD (vertebrate, fly, worm), spindle orientation (vertebrate, fly), chromosome segregation (vertebrate, worm), spindle positioning (worm) (Du et al., 2001; Srinivasan et al., 2003; Morin and Bellaïche, 2011) | Non-syndromic deafness (Walsh et al., 2010), brain malformations and deafness in Chudley-McCullough syndrome (Doherty et al., 2012) | GoLoco motif, tetratricopeptide (TPR) domains |
| insc | insc | – | Spindle orientation (vertebrate, fly), asymmetric cell division (fly) (Morin and Bellaïche, 2011) | – | Armadillo repeats |
| htt | htt | F21G4.6a | Neuronal transport, spindle orientation (vertebrate, fly) (Gunawardena et al., 2003; Godin and Humbert, 2011) | The Huntington’s Disease Collaborative Research Group (1993) | Polyglutamine tract, polyproline sequence, HEAT repeats |
| magoh | mago | mag-1 | RNA processing (vertebrate, fly worm), RNA localization (vertebrate, fly), spindle orientation and integrity, genomic stability (vertebrate), cytoskeleton organization (fly) (Li et al., 2000; Kataoka et al., 2001; Palacios, 2002; Le Hir and Andersen, 2008; Silver et al., 2010) | – | Mago nashi domain |
| apc | apc1, apc2 | apr-1 | Wnt signaling, ACD, microtubule stability (vertebrate, fly, worm), spindle orientation (vertebrate, fly), chromosome segregation, tumor suppressor (vertebrate) (Yamashita et al., 2003; Mizumoto and Sawa, 2007; McCartney and Näthke, 2008; Bahmanyar et al., 2009) | Familial adenomatous polyposis (FAP), gastrointestinal tumors (Minde et al., 2011) | Armadillo repeats, oligomerization domain, CRM1, β-catenin, microtubule-binding domains, |
| vegf | pvf1, pvf2, pvf3 | pvf-1 | Cell migration (vertebrate, fly), growth factor, oncogene, spindle orientation, angiogenesis (vertebrate) (Duchek et al., 2001; Tarsitano et al., 2006; Beck et al., 2011; Sitohy et al., 2012) | Epithelia skin cancer (Beck et al., 2011) | PDGF domain |
| vhl | vhl | vhl-1 | HIF1α regulation (vertebrate, fly, worm), microtubule stability, endocytosis, cell migration (vertebrate, fly), tumor suppressor, spindle orientation, genome integrity (vertebrate) (Thoma et al., 2009; Hsu, 2012) | Renal cell carcinoma (Kaelin, 2008) | Cullin E3 ubiquitin ligase |
| pten | pten | daf-18 | PI3K signaling (vertebrate, fly, worm), tumor suppressor, spindle orientation, genome integrity, cell growth (vertebrate), cell growth, actin cytoskeleton organization, (fly) (Ogg and Ruvkun, 1998; Stocker and Hafen, 2000; von Stein et al., 2005; Toyoshima et al., 2007; Hollander et al., 2011) | PTEN hamartoma tumor syndromes (PHTS) (Hollander et al., 2011) | Protein and lipid phosphatase |
| mcph1/microcephalin/brit1 | mcph1 | – | DNA damage response, centrosome integrity, chromosome segregation (vertebrate, fly), spindle orientation (vertebrate) (Thornton and Woods, 2009; Gruber et al., 2011) | Microcephaly (Jackson et al., 2002) | BRCA1 C-terminal (BRCT) domains |
| mcph2/wdr62 | – | – | Centrosome integrity, spindle orientation, chromosome alignment (vertebrate) (Bogoyevitch et al., 2012) | Microcephaly, lissencephaly, schizencephaly (Bilgüvar et al., 2010; Nicholas et al., 2010; Yu et al., 2010) | WD40 repeats |
| mcph3/cdk5rap2/cep215 | cnn | – | Centrosome assembly, spindle orientation, chromosome segregation (vertebrate, fly), DNA damage response (vertebrate) (Siller and Doe, 2008; Megraw et al., 2011) | Microcephaly (Bond et al., 2005) | Coiled-coil domains, centrosomin motives (CM) 1 and 2 |
| mcph4/cep152 | asl | – | Centriole formation and duplication (vertebrate, fly), genome integrity (vertebrate) (Kalay et al., 2011; Brito et al., 2012) | Microcephaly (Guernsey et al., 2010), Seckel syndrome (Kalay et al., 2011) | Coiled-coil domains |
| mcph5/aspm/calmbp1 | asp | aspm-1 | Spindle assembly, spindle orientation, cytokinesis (vertebrate, fly), the integrity of spindle poles and the central spindle (fly), meiotic spindle orientation (worm) (Varmark, 2004; van der Voet et al., 2009; Higgins et al., 2010) | Microcephaly (Bond et al., 2002), tumorigenesis (Lin et al., 2008) | Calponin homology (CH) domains, IQ-repeat motifs |
| mcph6/cenpj/cpap | sas4 | sas-4 | Centriole duplication (vertebrate, fly, worm), spindle orientation (vertebrate), ACD (fly) (Leidel and Gönczy, 2005; Basto et al., 2006; Kitagawa et al., 2011; Brito et al., 2012) | Microcephaly (Bond et al., 2005), Seckel syndrome (Al-Dosari et al., 2010) | Coiled-coil motives, PN2-3 domain, T-complex protein 10 (TCP) domain |
| mcph7/stil/sil | ana2 | sas-5 | Centriole duplication (vertebrate, fly, worm), spindle orientation (vertebrate, fly), ACD (fly) (Leidel and Gönczy, 2005; Wang et al., 2011; Brito et al., 2012) | Microcephaly (Kumar et al., 2009), leukemia (Aplan et al., 1991) | Coiled-coil domain, STIL/ANA2 (STAN) motif |
| cep63 | – | – | Spindle assembly, mitotic entry, genome maintenance, centrosome duplication (vertebrate) (Smith et al., 2009; Löffler et al., 2011) | Microcephaly (Sir et al., 2011) | Coiled-coil domains |
In many cases genes mutated in these pathologies control spindle orientation at the cellular level. ACD, asymmetric cell division.
The function of the genes has not been characterized.