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Homeobox protein OTX2
Gene OTX2: OTX2_HUMAN
Homeobox protein OTX2 (Gene OTX2) Homo sapiens
NCBI/Entrez 5015
HGNC 8522
UniProt/Swiss-Prot/ UniProt/TrEMBL P32243,Q6GTV3, Q9HAW3
Ensembl ENSG00000165588
OMIM 600037
GeneCards GC14M056337
Synonyms: Orthodenticle homolog 2 (Drosophila)

 

Homeobox protein OTX2 (Gene OTX2)

The OTX2 (gene locus: Entrez: 14q21-q22; Ensembl/HGNC: 14q22.3) gene product, homeoprotein OTX2, is a paired homeobox (bicoid subfamily) transcription factor that exists in two isoforms, isoform 1 and isoform 2. Isoform 1 is 289 AA (31.6 kDa) protein with a 60 AA (38-97) DNA-binding homeobox and a 7 AA (95-101) polyGln region C-terminal to and overlapping the homeobox. Isoform 2 is 297 AA long protein wherein, the 8-AA sequence ‘GPWASCPA’ is inserted immediately C-terminal to Pro32, Courtois V, et al. (2003).

The homeobox transcription factors Otx1 and Otx2 are involved in fundamental processes of anterior neural patterning, Boyl PP, et al. (2001a, 2001b). Otx2 functions as a rostral head organizer, Makiyama Y, et al. (1997) that is important in the early specification of fore- and midbrain neuroectoderm, Simeone A. et al. (1998). Otx2 plays a major role in gastrulation and in the early specification of the anterior neural plate while Otx1 is mainly involved in corticogenesis, Acampora D, et al. (1999a, 1999b, 2000). Otx1 and Otx2 functions overlap in regions where both are expressed, Suda Y, et al. (1997). Otx2 is required beginning as early as gastrulation for proper head development, Zakin L, et al. (2000).

Otx2 is involved in the early anterior-posterior (A-P) patterning of the mouse epiblast, Kimura C, et al. (2001). It is expressed in the entire epiblast (embryonic ectoderm) of pre-streak embryos and in an anterior-posterior gradient within the hypoblast (primitive endoderm) of early steak embryos. Mallamaci A, et al. (1996). Otx2 expression in the endomesoderm (early to midstreak-stage) and ectoderm supports anterior neuroectoderm specification, Acampora D, et al. (1995), Simeone A and Acampora D, (2001). Otx2 functions in the anterior visceral endoderm to influence epiblast cells to differentiate into anterior neuroectoderm, Perea-Gomez A, et al. (2001). Later, it is found in the neuroectoderm of the presumptive forebrain and midbrain, Rhinn M, et al. (1998). The Otx2 expression domain covers the entire forebrain and midbrain, Matsuo I, et al. (1995) and contains the expression domains of the homeoboxes, Emx1, Emx2 and Otx1, Boncinelli E. et al. (1995).

The boundary between the caudal midbrain (mesencephalon) and hindbrain (rhombencephalon) (MHB) contains an organizing center called the isthmic organizer (IO). This center controls anterior hindbrain and midbrain regionalization through a genetic network of genes such as En2, Wnt1, Pax-2, Fgf8 and Gbx2, Garda AL, et al. (2001). Otx2 expression is a caudal limit marker of the midbrain/hindbrain boundary separating the mesencephalic and isthmo/cerebellar regions, Millet S, et al. (1996) where its expression relative to Gbx2 positions the isthmic organizer and encodes the midbrain fate within this region, Broccoli V, et al. (1999), Simeone A. (2000), Martinez S, (2001). Otx2 activates the MHB genetic network genes whereas Gbx2 negatively regulates Otx2 and MHB genes, Tour E, et al. (2002). The role of Otx2 as a regulator of the isthmic organizer and brain regionalization has been defined in several publications; Garda AL, et al. (2001), Martinez S, (2001), Tour E, et al. (2002, 2002b); Rhinn M, et al. (2005) and reviewed by Hidalgo-Sánchez M, et al. (2005).

Regional differentiation of the diencephalon thalamic complex, a sensory relay station, is regulated by an intervening boundary region between the prethalamus and the thalamus called the zona limitans intrathalamica (ZLI). This center is induced in a competence area establish by Otx1, Otx2 and posteriorly restricted by Irx1b, Scholpp S, et al. (2007).

Otx1 and Otx2 play a role in cerebellar regionalization during early and postnatal development. During postnatal development Otx1 is found in the external granular layer (EGL) within posterior cerebellar lobules and overlapping Otx2 in the mid-cerebellum. Otx1 helps define the spinocerebellum and pontocerebellum, Frantz GD, et al. (1994).

Otx2 regulates the development of various neuronal populations within the forebrain and midbrain including GABAergic, glutamatergic, Puelles E, et al. (2006) and dopaminergic neurons. Dopaminergic neurons located in the substantia nigra compacta (SNc) are the cells that degenerate in Parkinson’s disease (PD). Otx2 has been identified as a factor that along with Pax2, Pax5, Nkx2.2 and Nkx6.1 regulates the local identity of the ventral midbrain regions that give rise to substantia nigra compacta and ventral tegmentum, Simon HH, et al. (2003) by mechanisms that are under current study, Puelles E, et al. (2004), Vernay B, et al. (2005) and review Prakash N and Wurst W, (2006).

Otx2 is involved in the development of several sensory organs. It is required for development of olfactory cells of the nose, Mallamaci A, et al. (1996); the otic vesicle and cochlear ganglion of the auditory system, Morsli H, et al. (1999), Miyazaki H, et al. (2006) and the formation of the competent eye field within the anterior plate, Katahira T, et al. (2000), Zuber ME, et al. (2003).

Otx2 is essential for retinal photoreceptor cell fate determination and development of the pineal gland, Nishida A, et al. (2003), Akagi T, et al. (2004). Otx2 plays a functional role in the postnatal maturation of retinal photoreceptor and bipolar cells, Koike C, et al. (2007).

Sigma offers antibodies and shRNAs useful for the study of OTX2 gene products..


References:

Footnote: Gene Data Sources: HGNC, Entrez Gene, UniProt/Swiss-Prot, UniProt/TrEMBL, GDB, OMIM, GeneLoc, Ensembl.

 

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