Orthopedia, a novel homeobox-containing gene expressed in the developing CNS of both mouse and drosophila

Simeone, Antonio; D’Apice, Maria Rosaria; Nigro, Vincenzo; Casanova, Jordi; Graziani, Franco; Acampora, Dario; Avantaggiato, Virginia

doi:10.1016/0896-6273(94)90461-8

Cited by 179 publications

(164 citation statements)

References 46 publications

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“…However, Rax does not encode the paired-box motif. Interestingly, at the C terminus of the Rax protein, we found a 15-aa stretch that is homologous to the C terminus of the homeodomains of aristaless, cart1 (40), chx10, otp (42), and s8 (39) (Fig. 2B).…”

Section: Resultsmentioning

confidence: 97%

rax , a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina

Furukawa

Kozak

Cepko

1997

Proc. Natl. Acad. Sci. U.S.A.

340

289

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Development of the vertebrate eye has been found to require the activity of several genes encoding homeodomain proteins (Freund, C., Horsford, D. J. & McInnes, R. R. (1996) Hum. Mol. Genet. 5, 1471-1488). Some of these genes, or portions thereof, are highly conserved across phyla. In this paper, we report the identification of a novel homeobox gene, rax (retina and anterior neural fold homeobox), whose expression pattern suggests an important role in eye development. The predicted amino acid sequence of Rax comprises a protein with a paired-type homeobox, as well as the octapeptide that is found in many paired-type homeobox genes. In addition, in the C terminus of Rax, we found a 15-aa domain that we have named the OAR domain. This domain is also found in several other homeobox genes. In the early mouse embryo, rax is expressed in the anterior neural fold, including areas that will give rise to the ventral forebrain and optic vesicles. Once the optic vesicles form, rax expression is restricted to the ventral diencephalon and the optic vesicles. At later stages, rax expression is found only in the developing retina. After birth, the expression of rax is restricted to the zone of proliferating cells within the retina, and expression gradually decreases as proliferation declines. These findings suggest that rax is one of the molecules that define the eye field during early development and that it has a role in the proliferation and͞or differentiation of retinal cells.During vertebrate development, the central nervous system emerges as a highly complex, patterned structure with an enormous diversity of neuronal and glial cell types. The vertebrate retina is a relatively well described and accessible structure that provides an excellent model system for studies of patterning and cell fate determination within the central nervous system (1). In the early stages of eye development, the optic vesicles evaginate from the ventral forebrain, making contact with the overlying surface ectoderm at embryonic day 9 (E9) in the mouse. Subsequently, the optic vesicle invaginates to form the optic cup, while overlying surface ectoderm gives rise to the lens placode (2, 3). Retinal neurogenesis then proceeds within the inner layer of the optic cup. The mitotic progenitors within the optic cup line the surface apposed to the former lumen of the neural tube, in an area known as the ventricular zone (VZ). Postmitotic progeny of the retina migrate away from the VZ as they differentiate to form the laminar structure of the mature retina. While the different retinal cells are born in a sequence conserved among many species, more than one cell type is born at any one time (4). Lineage analyses in several species have shown that retinal progenitors remain multipotent throughout development (5-8).

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Section: Resultsmentioning

confidence: 97%

rax , a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina

Furukawa

Kozak

Cepko

1997

Proc. Natl. Acad. Sci. U.S.A.

340

289

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“…2F,G,L). To confirm and extend these results, we immunostained for the transcription factors retina and anterior neural fold homeobox (RAX) (Furukawa et al, 1997), orthopedia homeobox (OTP) (Simeone et al, 1994) and single-minded homolog 1 (SIM1) (Fan et al, 1996) (Fig. 2H-J).…”

Section: Self-patterning Of Hpscs Into Hypothalamic Progenitorsmentioning

confidence: 99%

Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

et al. 2015

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Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agoutirelated peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a 'self-patterning' strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases.

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“…Therefore, both the timing and location of Olf-1 expression suggest a role for Olf-1 in the postmitotic, neural cell that has commenced a course of differentiation. Olf-1 joins a small group of factors that have been found selectively in postmitotic cells, including Brn-3.2, OTP, and T-Brain (Simeone et al, 1994;Turner et al, 1994;Bulfone et al, 1995).…”

Section: Widespread Olf-1 Expression In Nervous Tissue Of the Developmentioning

confidence: 99%

Role of Olf-1 and Pax-6 Transcription Factors in Neurodevelopment

1996

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The Olf-1 transcription factor is expressed in olfactory sensory neurons where it regulates the expression of genes that encode components of the odorant signal transduction cascade and contributes to the terminal phenotype of these sensory neurons. We examined the pattern of expression of Olf-1 protein during mouse embryogenesis and observed Olf-1 expression transiently in a subset of neural precursor cells in the CNS and peripheral nervous system. The expression of Olf-1 protein was enriched in sensory components and coincided with postmitotic cells and the initiation of overt differentiation within the nervous system. The spatial and temporal patterns of Olf-1 expression during development suggest a role in neurogenesis that is common among different neural cell types. In parallel, the expression pattern of Pax-6, a transcription factor that is widely expressed in the developing nervous system, including the visual and olfactory systems, was examined with a C-terminal antibody. In the retina, Pax-6 protein is detected in the lens, the cornea, and the neural and pigmented retinas. In the olfactory epithelium, Pax-6 protein is expressed exclusively in cells of non-neuronal lineage, including sustentacular cells, basal cells, and Bowman's glands. The nonoverlapping, cellular localization patterns of Pax-6 and Olf-1 demarcate distinct cell lineages within the developing olfactory epithelium.

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Orthopedia, a novel homeobox-containing gene expressed in the developing CNS of both mouse and drosophila

Cited by 179 publications

References 46 publications

rax , a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina

rax , a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina

Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

Role of Olf-1 and Pax-6 Transcription Factors in Neurodevelopment

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