Abstract
prospero-related homeobox genes have been identified from various multi-cellular organisms and play important roles in development as a cell fate determinant. Mouse Prox1 is essential for embryogenesis and is required to differentiate horizontal cells in the retina. Here we describe a novel prospero family member, Prox2. Transcriptional reporter assays demonstrated that mouse Prox2 is a transcriptional activator and the N-terminal region has been identified as an activation domain. The expression of mouse Prox2 was detected in postnatal eyes and adult testes as well as embryos. To investigate the in vivo role of Prox2, we generated the Prox2 mutant allele, Prox2 −, by homologous recombination in mouse ES cells. Prox2 − lacks the first coding exon that encodes a translational start site and a part of homeodomain. In spite of the Prox2 expression during embryogenesis, Prox2 − homozygous mutant mice were born at the expected Mendelian ratio without overt abnormalities. Histological analyses revealed that Prox2 − homozygous eyes retained the organized layer structure including three nuclear layers and differentiated horizontal cells. Prox2 − homozygous mutant males produced elongated spermatids and were fertile. These results demonstrate that mouse Prox2 is dispensable for embryonic development, horizontal cell generation and fertility in contrast to mouse Prox1.
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References
Bi X, Kajava AV, Jones T, Deminenko ZN, Mortin MA (2003) The carboxy terminus of Prospero regulates its subcellular localization. Mol Cell Biol 23:1014–1024
Cook T (2003) Cell diversity in the retina: more than meets the eye. BioEssays 25:921–925
Cui W, Tomarev SI, Piatigorsky J, Chepelinsky AB, Duncan MK (2004) Mafs, Prox1, and Pax6 can regulate chicken βB1-Crystallin gene expression. J Biol Chem 279:11088–11095
Del Bene F, Wittbrodt J (2004) Cell cycle control by homeobox genes in development and diseases. Semin Cell Dev Biol 16:449–460
Demidenko Z, Badenhorst P, Jones T, Bi X, Mortin MA (2001) Regulated nuclear export of the homeodomain transcription factor Prospero. Development 128:1359–1367
Dyer MA, Livesey FJ, Cepko CL, Oliver G (2003) Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nat Genet 34:53–58
Glasgow E, Tomarev SI (1998) Restricted expression of the homeobox gene prox1 in developing zebrafish. Mech Dev 76:175–178
Griffiths RL, Hidalgo A (2004) Prospero maintains the mitotic potential of glial precursors enabling them to respond to neurons. EMBO J 23:2440–2450
Hassan B, Li L, Bremer KA, Chang W, Pinsonneault J, Vaessin H (1997) Prospero is a panneural transcription factor that modulates homeodomain protein activity. Proc Natl Acad Sci USA 94:10991–10996
Hirata J, Nakagoshi H, Nabeshima Y, Matsuzaki F (1995) Asymmetric segregation of the homeodomain protein Prospero during Drosophila development. Nature 377:627–630
Hong YK, Detmar M (2003) Prox1, master regulator of the lymphatic vasculature phenotype. Cell Tissue Res 314:85–92
Hong YK, Harvey N, Noh YH, Hirakawa S, Detmar M, Oliver G (2002) Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev Dyn 225:351–357
Li L, Vaessin H (2000) Pan-neural Prospero terminates cell proliferation during Dorosophila neurogenesis. Genes Dev 14:147–151
Liu YW, Gao W, The HL, Tan JH, Chan WK (2003) Prox1 is a novel coregulator of Ff1b and is involved in the embryonic development of the zebra fish interrenal primordium. Mol Cell Biol 23:7243–7255
Manning L, Doe CQ (1999) Prospero distinguishes sibling cell fate without asymmetric localization in the Drosophila adult external organ lineage. Development 126:2063–2071
O’Gorman S, Dagenais NA, Qian M, Marchuk Y (1997) Protamine-Cre recombinase transgenes efficiently recombine target sequences in the male germ line of mice, but not in embryonic stem cells. Proc Natl Acad Sci USA 94:14602–14607
Ohtoshi A, Behringer RR (2004) Neonatal lethality, dwarfism, and abnormal brain development in Dmbx1 mutant mice. Mol Cell Biol 24:7548–7558
Ohtoshi A, Justice MJ, Behringer RR (2001) Isolation and characterization of Vsx1, a novel mouse CVC paired-like homeobox gene expressed during embryogenesis and retina. Biochem Biophys Res Commun 286:133–140
Ohtoshi A, Nishijima I, Justice MJ, Behringer RR (2002) Dmbx1, a novel evolutionarily conserved paired-like homeobox gene expressed in the brain of mouse embryos. Mech Dev 110:241–244
Ohtoshi A, Wang SW, Maeda H, Saszik SM, Frishman LJ, Klein WH, Behringer RR (2004) Regulation of retinal cone bipolar cell differentiation and photopic vision by the CVC homeobox gene Vsx1. Curr Biol 14:530–536
Ohtoshi A, Otoshi H (2001) Analysis of β3-endonexin mutants for their ability to interact with cyclin A. Mol Genet Genomics 266:664–671
Qin JB, Gao DB, Jiang QF, Zhou Q, Kong YY, Wang Y, Xie YH (2004) Prospero-related homeobox (Prox1) is a corepressor of human liver receptor homolog-1 and suppress the transcription of the cholesterol 7-α-hydroxylase gene. Mol Endocrinol 18:2424–2439
Sosa-Pineda B, Wigle JT, Oliver G (2000) Hepatocyte migration during liver development requires Prox1. Nat Genet 25:254–255
Spana EP, Doe CQ (1995) The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila. Development 121:3187–3195
Tomarev SI, Zinovieva RD, Chang B, Hawes NL (1998) Characterization of the mouse Prox1 gene. Biochem Biophys Res Commun 30:684–689
Wigle JT, Chowdhury K, Gruss P, Oliver G (1999) Prox1 function is required for lens-fibre elongation. Nat Genet 21:318–322
Wigle JT, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn MD, Jackson DG, Oliver G (2002) An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J 21:1505–1513
Wigle JT, Oliver G (1999) Prox1 function is required for the development of the murine lymphatic system. Cell 98:769–778
Zinovieva RD, Duncan MK, Johnson TR, Torres RR, Polymeropoulos MH, Tomarev SI (1996) Structure and chromosomal localization of the human homeobox gene Prox1. Genomics 35:517–522
Acknowledgements
We thank Steve O’Gorman for PC3 ES cells, Allan Bradley for SNL 76/7 STO cells, Jennifer Voss for assistance with histology, Wenning Zhao for Western blotting, and Tara McArthur for critical reading of the manuscript.
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Nishijima, I., Ohtoshi, A. Characterization of a novel prospero-related homeobox gene, Prox2 . Mol Genet Genomics 275, 471–478 (2006). https://doi.org/10.1007/s00438-006-0105-0
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DOI: https://doi.org/10.1007/s00438-006-0105-0