Early growth response protein 2 (EGR2), also known asKrox20, is atranscription factor encoded by theEGR2gene in humans. It is highly expressed in migratingneural crest cells and later in neural crest-derived cells of the cranial ganglia.[5][6][7] Expression ofEGR2 is restricted to earlyhindbrain development,[6][8] and the gene is evolutionarily conserved among vertebrates, including humans, mice, chicks, and zebrafish.[9] The conservation of its amino acid sequence and embryonic expression pattern underscores its essential role in hindbrain segmentation and neural differentiation.[7][10][11][12]
EGR2 acts as atranscription factor that regulates gene expression during neural development and peripheral nerve myelination. It binds to specific DNA sequences via its zinc finger motifs to control target genes essential forSchwann cell differentiation andmyelin sheath formation.[13] It is also expressed in osteoprogenitor cells and has been implicated in the proliferation ofEwing sarcoma–derived cell lines, suggesting a role in both bone biology and tumorigenesis.[14][15]
Mutations inEGR2 are associated with several hereditary demyelinating neuropathies, includingCharcot–Marie–Tooth disease type 1D,[13]Dejerine–Sottas disease,[16] and congenital hypomyelinating neuropathy.[17]Recent studies have also suggested thatEGR2 expression in hair follicle stem cells may influence hair maintenance and pigmentation, with loss of Krox20-expressing cells contributing tomale-pattern baldness andgraying hair.[18]
Deletion ofEgr2 in mice results in loss of protein-coding capacity, including the DNA-binding domain, leading to perinatal lethality and severe hindbrain malformations.[6][8] These defects include aberrant formation of cranial sensory ganglia, fusion of the trigeminal (V), facial (VII), and auditory (VIII) nerves, and disorganization of their proximal roots as they enter the brainstem.[19][20][21]
^abcBradley LC, Snape A, Bhatt S, Wilkinson DG (January 1993). "The structure and expression of the Xenopus Krox-20 gene: conserved and divergent patterns of expression in rhombomeres and neural crest".Mechanisms of Development.40 (1–2):73–84.doi:10.1016/0925-4773(93)90089-g.PMID8443108.S2CID20347966.
^Bhat RV, Worley PF, Cole AJ, Baraban JM (April 1992). "Activation of the zinc finger encoding gene krox-20 in adult rat brain: comparison with zif268".Brain Research. Molecular Brain Research.13 (3):263–6.doi:10.1016/0169-328x(92)90034-9.PMID1317498.
^Boerkoel CF, Takashima H, Bacino CA, Daentl D, Lupski JR (July 2001). "EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy".Neurogenetics.3 (3):153–7.doi:10.1007/s100480100107.PMID11523566.S2CID32746701.
^Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, et al. (April 1998). "Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies".Nature Genetics.18 (4):382–4.doi:10.1038/ng0498-382.PMID9537424.S2CID25550479.
^Frohman MA, Boyle M, Martin GR (October 1990). "Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm".Development.110 (2):589–607.doi:10.1242/dev.110.2.589.PMID1983472.
^Nieto MA, Bradley LC, Wilkinson DG (1991). "Conserved segmental expression of Krox-20 in the vertebrate hindbrain and its relationship to lineage restriction".Development. Suppl 2:59–62.doi:10.1242/dev.113.Supplement_2.59.hdl:10261/32226.PMID1688180.
Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, et al. (April 1998). "Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies".Nature Genetics.18 (4):382–4.doi:10.1038/ng0498-382.PMID9537424.S2CID25550479.
Timmerman V, De Jonghe P, Ceuterick C, De Vriendt E, Löfgren A, Nelis E, et al. (June 1999). "Novel missense mutation in the early growth response 2 gene associated with Dejerine-Sottas syndrome phenotype".Neurology.52 (9):1827–32.doi:10.1212/wnl.52.9.1827.PMID10371530.S2CID11569651.
Pareyson D, Taroni F, Botti S, Morbin M, Baratta S, Lauria G, et al. (April 2000). "Cranial nerve involvement in CMT disease type 1 due to early growth response 2 gene mutation".Neurology.54 (8):1696–8.doi:10.1212/wnl.54.8.1696.hdl:2434/531868.PMID10762521.S2CID28404231.
Yoshihara T, Kanda F, Yamamoto M, Ishihara H, Misu K, Hattori N, et al. (March 2001). "A novel missense mutation in the early growth response 2 gene associated with late-onset Charcot--Marie--Tooth disease type 1".Journal of the Neurological Sciences.184 (2):149–53.doi:10.1016/S0022-510X(00)00504-9.PMID11239949.S2CID19693658.
Boerkoel CF, Takashima H, Bacino CA, Daentl D, Lupski JR (July 2001). "EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy".Neurogenetics.3 (3):153–7.doi:10.1007/s100480100107.PMID11523566.S2CID32746701.
Musso M, Balestra P, Taroni F, Bellone E, Mandich P (February 2003). "Different consequences of EGR2 mutants on the transactivation of human Cx32 promoter".Neurobiology of Disease.12 (1):89–95.doi:10.1016/S0969-9961(02)00018-9.PMID12609493.S2CID29600641.
Numakura C, Shirahata E, Yamashita S, Kanai M, Kijima K, Matsuki T, et al. (June 2003). "Screening of the early growth response 2 gene in Japanese patients with Charcot-Marie-Tooth disease type 1".Journal of the Neurological Sciences.210 (1–2):61–4.doi:10.1016/S0022-510X(03)00028-5.PMID12736090.S2CID36723641.
