Table 1Functional analysis of the vertebrate Gli proteins in vivo

GeneOrganismMutationSurvivalTissueEffectRefs.
Gli1 Mouse Gli1zfd/zfd ViableNo phenotype41, 64
(Gli1 nul)
Gli1lacZ/lacZ ViableNo phenotype63
(Gli1 nul)
ZebrafishdetourNeural tubeVentral CNS patterning defects212, 226
(Gli1 nul)ForebrainReduced ventral markers of diencephalon
PituitaryReduced expression of adenohypophysis markers
Gli2 HumanvariousForebrainSpectrum of holoprosencephaly features218
(?)PituitaryAbnormal pituitary formation and function
Mouse Gli2zfd/zfd Perinatal lethalNeural tubeLack of floor plate, reduced V3 interneurons41, 64, 65
(Gli2 nul)Oligodendrocyte specification216
ForebrainMild holoprosencephaly66, 190
Thinner telencephalic vesicles, smaller tectum and cerebellum190
LungLung hypoplasia and lobulation defects67
ForegutTracheo-oesophageal fistula67
HindgutImperforate anus with recto-urethral fistula199
SkeletonAbsence of vertebrae and intervertebral discs66
Cleft palate, delayed ossification of skull
Reduced length of limbs and sternum
SkinHair follicle arrest99
TeethAbnormal maxillary incisors66, 119
MammaryDuctal hyperplasia in explants124
Gli2gli1/- ViableNeural tubeRescue ventral cell types and notochord regression defects of Gli2-/- 57
(GliACT med)LungsAccessory lobe rescued and increased proliferation
SkinProgressive alopecia >3 mos
Gli2gli1/gli1 Postnatal lethalNeural tubeSimilar to Gli2gli1/-rescue; no expansion of ventral cell types57
(GliACT high)CNSStiffness of movement and loss of hindlimb coordination
SkinEarly and severe alopecia and more severe
Gli2 Mouse Gli2gli3/- Perinatal lethalNeural tubeIdentical to Gli2-/-; lack of floor plate, reduced V3 interneurons58
(GliACT low)
Gli2gli3/gli3 Perinatal lethalNeural tubePartial rescue of FP cells, V3 interneurons and motor neurons58
(GliACT med)(requires Gli1 induction: no rescue in Gli2gli3/gli3Gli1lacz/lacz)
Zebrafish you-too (Gli2ΔC)Neural tubeMidline and axonal guidance defects212, 222, 225, 226
ForebrainVentral differentiation defects226
PituitaryLoss of adenohypophysis & ectopic lens formation214, 219, 226
SomitesLack of horizontal myoseptum; defects in slow muscle formation208, 226
Gli3 HumanGCPSSkeletonPost- and pre-axial polydactyly, syndactyly210, 223, 224
(GLI3 heterozygous)Craniofacial defects and hypertelomerism Macrocephaly
PHSForebrainHypothalamic hamartoma and pituitary disfunction52, 211
(Gli3ΔC )ForegutLaryngotracheal cleft and malformed epiglottis
KidneyRenal anomalies
HindgutImperforate anus
SkeletonPost-axial and central polydactyly
AppendageHypoplastic nails
PAP-ASkeletonPost-axial polydactyly217
(GLI3 REP mild)
Mouse Gli3xtj/xtj Perinatal lethalNeural tubeDorsal expansion of V0-V2 interneurons73, 103
(Gli3 nul)Neural tube closure defects & edema68
ForebrainExencephaly and choroid plexus defects190, 209
Ventralized telecephalon215, 220
LungAltered shape and size67, 178
HindgutAnal stenosis and ectopic anus199, 213
Perinatal lethalSkeletonPolydactyly, syndactyly66, 68
Craniofacial defects and unfused sternum66, 68
Shortening and thickening of limbs66
Gli3 Mouse Gli3xtj/xtj Perinatal lethalSkinSupernumerary vibrissae and pelage follicles99
(Gli3 nul)EyesPoorly developed eyes71
Gli3phs/phs Perinatal lethalForegutEpiglottis and larynx defects207
(Gli3ΔC )KidneyHypoplastic and dysmorphic defects and lack of adrenal glands
HindgutGastrointestinal defects and imperforate anus
SkeletonPolydactyly, syndactyly
Proximal-distal shortening of limbs
Premature skeletal mineralization
ZebrafishGli3 morpholinoCNSPatterning defects of neural tube and brain221
EyeReduced retinal ganglion cell differentiation
Gli1/Gli2 Mouse Gli1zfd/zfd PostnatalCNSReduction of floor plate and V3 interneurons64
Gli2zfd/+ lethalityBehavioral and neurological defects
LungsHypoplastic and lobular defects
GenitalsMales: undescended testes and incomplete external development
Gli1zfd/zfd EmbryonicCNSLack all V3 interneurons and floor plate64
Gli2zfd/zfd lethality
LungsDelayed morphogenesis and severe hypoplasia
PituitaryAbsent
SkeletonPost-axial nubbin present on all limbs
Gli1/Gli3 Mouse Gli1zfd/zfd ViableSkeletonPost-axial polydactyly, but phenotype identical to Gli3xtj/+ 64
Gli3xtj/-
Gli2/Gli3 Mouse Gli2zfd/zfd Perinatal lethalityNeural tubeExpanded motor neuron progenitor domain, normal MN develop53, 58
Gli3xtj/- SkeletonMore severe reduction in stylopod and zeugopod length66
More severe pre-axial polydactyly phenotype, post-axial nubbin
More severe defects in vertebral column and sternum
Gli2/Gli3 Mouse Gli2zfd/zfd Perinatal lethalityTeethMandible defects, maxillary incisors arrested and small molars66, 119
Gli3xtj/- Foregutesophageal atresia with tracheo-oesophageal fistula67
LungSeverely hypoplastic lung with lobulation defects
Gli2/Gli3 Mouse Gli2zfd/zfd Perinatal lethalityHindgutPersistent cloaca199
Gli3xtj/- Hair folliclesMore severe arrest of hair follicle development99
Gli2zfd/zfd Gli3xtj/xtj Embryonic lethality E10.5Neural tubeLoss of ventral cell types (required for proliferation and positioning) and extension of dorsal identity, hyperproliferation58
SomitesDefects in sclerotome and myotome development59
ForegutNo trachea or esophagus form67
LungsNo lung formation
Ptc1/Gli1 Mouse Ptc1-/-Gli1zfd/zfd E9.5Neural tubeNo rescue of ventralized Ptc1-/- phenotype 63
Ptc1/Gli2 Mouse Ptc1-/-Gli2zfd/zfd >E9.5Neural tubeVentralized Ptc1-/- phenotype suppressed60, 63
MesodermReduction of Hh responses63
Ptc1/Gli3 Mouse Ptc1-/-Gli3xtj/xtj E9.5Neural tubeNo rescue of ventralized Ptc1-/- phenotype60
Shh/Gli2 Mouse Shh-/-Gli2zfd/zd Perinatal lethalNeural tubeNo rescue of Shh-/- phenotype: cyclopia, loss of ventral cell types57
Shh/Gli3 Mouse Shh-/-Gli3xtj/+ Perinatal lethalNeural tubeSome rescue of ventral cell types69, 73, 103
CNSTelencephalon partially rescued, increased progenitor proliferationC.c.H. and P.D., unpubl.
CraniofacialTwo eyes and more defined frontonasal mass71; P.M. andC.c.H. unpubl.
SkeletalImproved distal limb development and autopod number71, 72, 74
Hair follicleVibrissae and pelage follicle pattern improvementsP.M. andC.c.H. unpubl.
Shh-/-Gli3xtj/xtjs Perinatal lethalNeural tubeRescue of all ventral cell types, patterning defects remain69, 73, 103
CNSExencephaly, high progenitor proliferationC.c.H. and P.D., unpubl.
CraniofacialTwo eyelids with hypomorphic eyes and large frontonasal mass71; P.M. and C.c.H. unpubl.
SkeletalDistally complete limb and polydactylous (duplications)71, 72, 74
Hair folliclePartial rescue of vibrissae and pelage follicle developmentP.M. and C.c.H., unpubl.

From: Splitting Hairs: Dissecting the Roles of Gli Activator and Repressor Functions during Epidermal Development and Disease

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