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Gene Review

Otp  -  orthopedia homolog (Drosophila)

Mus musculus

Synonyms: Homeobox protein orthopedia
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High impact information on Otp

  • Homozygous Otp(-/-) mice die soon after birth and display progressive impairment of crucial neuroendocrine developmental events such as reduced cell proliferation, abnormal cell migration, and failure in terminal differentiation of the parvocellular and magnocellular neurons of the aPV, PVN, SON, and ARN [1].
  • In mouse, Otp is expressed only in restricted domains of the developing forebrain, hindbrain, and spinal cord [2].
  • From these results, we conclude that the Otp homeodomain gene is involved in short-range cell signalling within the oral ectoderm for patterning the endoskeleton of the larva through epithelial-mesenchymal interactions [3].
  • Sim1, Arnt2, and Otp genes are essential for terminal differentiation of these neurons [4].
  • Absence of elevated apoptotic activity, but reduced cell proliferation together with the ectopic activation of Six3 expression in the presumptive PVN, indicates a critical role for Otp in terminal differentiation and maturation of these neuroendocrine cell lineages [5].

Biological context of Otp

  • Hypothalamic nuclei, including the anterior periventricular (aPV), paraventricular (PVN), and supraoptic (SON) nuclei strongly express the homeobox gene Orthopedia (Otp) during embryogenesis [5].
  • Otp maps to mouse chromosome 13 [6].
  • The deduced amino acid sequence of the open reading frame of the human cDNA is 99% homologous to mouse Otp and demonstrates a high degree of conservation when compared to sea urchin and Drosophila [7].

Anatomical context of Otp

  • Otp employs distinct regulatory mechanisms to modulate the expression of specific molecular markers in the developing hypothalamus [5].
  • By using Otp as a marker, these goosecoid-positive cells were found to constitute a small area just beside the paraventricular nucleus [8].
  • Molecularly, the loss of the tectum is demonstrated by an expanded expression of Pax6, (the molecular determinant of posterior commissure), and a rostral shift of the territory of expression of Gbx2 and Otp (markers for the pons), towards the caudal diencephalon [9].
  • In an effort to identify novel HD genes involved in the development of the human CNS, we have cloned, characterized, and mapped the human homologue of the murine HD gene Orthopedia (Otp), whose product is found in multiple cell groups within the mouse hypothalamus, amygdala, and brain stem [7].

Regulatory relationships of Otp

  • In contrast, the regulation of Brn4 which is also expressed in the SON and PVN is independent of Otp function [5].

Other interactions of Otp

  • Hence no strong evidence links Otp and Brn4 in the same regulatory pathway [5].
  • The involvement of Otp and Sim1 in specifying specific hypothalamic neurosecretory cell lineages is shown to operate via distinct signaling pathways that partially overlap with Brn2 [5].


  1. Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene. Acampora, D., Postiglione, M.P., Avantaggiato, V., Di Bonito, M., Vaccarino, F.M., Michaud, J., Simeone, A. Genes Dev. (1999) [Pubmed]
  2. Orthopedia, a novel homeobox-containing gene expressed in the developing CNS of both mouse and Drosophila. Simeone, A., D'Apice, M.R., Nigro, V., Casanova, J., Graziani, F., Acampora, D., Avantaggiato, V. Neuron (1994) [Pubmed]
  3. Spatially restricted expression of PlOtp, a Paracentrotus lividus orthopedia-related homeobox gene, is correlated with oral ectodermal patterning and skeletal morphogenesis in late-cleavage sea urchin embryos. Di Bernardo, M., Castagnetti, S., Bellomonte, D., Oliveri, P., Melfi, R., Palla, F., Spinelli, G. Development (1999) [Pubmed]
  4. Sim2 contributes to neuroendocrine hormone gene expression in the anterior hypothalamus. Goshu, E., Jin, H., Lovejoy, J., Marion, J.F., Michaud, J.L., Fan, C.M. Mol. Endocrinol. (2004) [Pubmed]
  5. The murine Otp homeobox gene plays an essential role in the specification of neuronal cell lineages in the developing hypothalamus. Wang, W., Lufkin, T. Dev. Biol. (2000) [Pubmed]
  6. Otp maps to mouse chromosome 13. Wang, W., Lufkin, T. Mamm. Genome (1997) [Pubmed]
  7. Identification, chromosomal assignment, and expression analysis of the human homeodomain-containing gene Orthopedia (OTP). Lin, X., State, M.W., Vaccarino, F.M., Greally, J., Hass, M., Leckman, J.F. Genomics (1999) [Pubmed]
  8. Survey for paired-like homeodomain gene expression in the hypothalamus: restricted expression patterns of Rx, Alx4 and goosecoid. Asbreuk, C.H., van Schaick, H.S., Cox, J.J., Smidt, M.P., Burbach, J.P. Neuroscience (2002) [Pubmed]
  9. Pax2/5 and Pax6 subdivide the early neural tube into three domains. Schwarz, M., Alvarez-Bolado, G., Dressler, G., Urbánek, P., Busslinger, M., Gruss, P. Mech. Dev. (1999) [Pubmed]
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