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FLASH GENE

Symbol

LHX2

contributors: mct/npt/pgu - updated : 30-03-2018

HGNC name	LIM homeobox 2
HGNC id	6594

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004789 5 - 2416 NP_004780 - 406 - 1999 10593900

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel       moderately Digestive intestine small intestine     moderately Nervous brain diencephalon hypothalamus   highly Homo sapiens   nerve       highly Visual eye anterior segment conjunctiva     Homo sapiens   eye anterior segment cornea     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Nervous epithelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	nervous system, Rathke pouch, extensively expressed in the developing ventral diencephalon, including the infundibulum and the posterior lobe of the pituitary

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two cysteine-rich (LIM) Zn2+ binding domains
	an helix-turn-helix homeobox DNA-binding domain
	C-terminal LIM domain that with the homeodomain were required for its growth-suppressive activity

HOMOLOGY

interspecies	ortholog to rattus Lhx2 (99pc)
	ortholog to murine Lhx2 (99pc)

Homologene

FAMILY

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	acting as a tissue specific transcriptional activator of the alpha subunit of glycoprotein hormones
	involved in the control of cell differentiation in developing lymphoid and neural cell types
	acting as a classic selector gene and essential intrinsic determinant of cortical identity
	required for optic vesicle patterning and lens formation in part by regulating BMP signaling in an autocrine manner in the optic neuroepithelium and in a paracrine manner in the lens ectoderm
	regulates a regional-fate decision by telencephalic progenitors during a critical period that ends as they differentiate from neuroepithelial cells to neuronogenic radial glia
	essential role in the regulation of posterior pituitary development
	unique role in the hippocampus during the phase of active neurogenesis
	key regulator of the neuron-astrocyte cell fate switch in the developing hippocampus but it is an unexpected spatial selectivity within the telencephalon for this critical function
	is able to suppress baseline activation as well as NFIA-induced activation of the GFAP promoter
	LHX2 and LHX9 determine neuronal differentiation and compartition in the caudal forebrain by regulating Wnt signaling
	regulates the development of the forebrain hem system
	plays a critical role in human neural differentiation
	LHX2 regulates the transcription of downstream intrinsic and extrinsic molecules that are essential for early neural differentiation
	is a key regulator of retinal progenitor cells (RPCs) properties that contribute to the ordered production of multiple cell types during retinal tissue formation
	essential roles for LHX2 in glial wedge (GW), hippocampal commissure, and corpus callosum formation, suggesting that defects in radial GW progenitors can give rise to agenesis of the corpus callosum (ACC)
	LHX2 is a key intrinsic regulator of tanycyte differentiation, sustaining RAX-dependent activation of tanycyte-specific genes while also inhibiting expression of ependymal cell-specific genes
	critical roles for LHX2 that acts as one of the terminal selector genes in controlling principal properties of neurons
	regulates the cortex size by maintaining the cortical progenitor proliferation and delaying the initiation of neurogenesis
	is required for maintenance of the corneal epithelial cell compartment and the limbal barrier
	LHX2 not only directly regulates expression of NOTCH signaling pathway components, but also acts together with the gliogenic NOTCH pathway to drive Müller glia (MG) specification and differentiation
	neuroretinal expression of LHX2 and neuroretina-derived FGF factors are crucial for lens fiber development
	function for LHX2 in regulating dorsoventral patterning in the telencephalon
	is capable of blocking proliferation of T-ALL-derived cells by both LMO2-dependent and -independent means
	is a fundamental, temporally dynamic, always necessary, and often sufficient factor in a range of critical developmental phenomena

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development , nervous system

text

Rathke

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	CBP/p300 interactive transactivator
	SSBP3 inhibits LHX2 and LDB1 turnover, stimulates assembly of this DNA-binding complex, promotes its recruitment to the CGA promoter, and enhances CGA transcription
	LHX2 binds to a conserved motif in the ROBO3 gene, suggesting that LHX2/LHX9 regulate directly the expression of ROBO3
	interacting with PAX6 (LHX2 and PAX6 transcription factors operate in a concerted manner during retinal development to promote transcriptional activation of the SIX6 homeobox-gene in primitive and mature retinal progenitors)
	able to suppress NFIA-induced astrogliogenesis robustly
	highly specific point of interaction of LHX2 with the NOTCH pathway in suppressing the astrogliogenic effects of the NOTCH target NFIA
	influences axon guidance and the topographical sorting of axons by regulating the expression of ROBO1 and ROBO2 guidance receptors, which are essential for these axons to establish correct connections in the cerebral cortex
	histone modification and E2F1 binding are integral parts of the mechanism for LHX2 gene expression
	LMO3 is a putative direct transcriptional target of GBX2 (GBX2 regulates the LIM transcriptional codes comprising LHX2, LHX9 and LMO3, which subsequently control the differential expression of ROBO1 and ROBO2 in the thalamus
	regulates neural differentiation at two levels: first, it promotes expression of PAX6 by binding to its active enhancers, and second, it attenuates BMP and WNT signaling by promoting expression of the BMP and WNT antagonist CER1, to inhibit non-neural differentiation
	LHX2 is required for the expression of transcription factor PAX6, axon guidance molecule EFNA5, and the receptor NMDAR1
	LHX2 promotes tumor growth and metastasis by inducing autocrine and paracrine PDGFB signaling
	is required for CTNNB1 function in maintaining cortical progenitor proliferation and controls the timing of cortical neurogenesis
	confers neuronal competency for activity-dependent dendritic development in L4 neurons by inducing the expression of BTBD3
	LHX2 binds a highly conserved putative enhancer of DMRTA2, suggesting an evolutionarily conserved regulatory relationship between these factors
	overexpression of PAX6 can substitute for LHX2 in the regulation of the neuronal versus glial cell fate in the developing hippocampus
	control of LHX2 function by LDB1 and RLIM underpins the coordinated differentiation of neurons and Müller glia in postnatal retina

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   translocation --low   maybe inactivated by the BCR-ABL translocation in chronic myelogenous leukemia

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	deletion of Lhx2 with Emx1-cre at embryonic day 10.5 (E10.5) altered the fates of progenitors, causing them to generate three-layer cortex, phenocopying olfactory cortex rather than lateral neocortex
	Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification