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Gene Review

Prox1  -  prospero homeobox 1

Mus musculus

Synonyms: A230003G05Rik, Homeobox prospero-like protein PROX1, PROX-1, Prospero homeobox protein 1
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Disease relevance of Prox1


High impact information on Prox1


Biological context of Prox1

  • Prox1 activity controls pancreas morphogenesis and participates in the production of "secondary transition" pancreatic endocrine cells [8].
  • Here we show that the divergent homeodomain transcription factor Prox1 is a novel, crucial regulator of mouse pancreas organogenesis [8].
  • Hence, it is possible that Prox1 contributes to the allocation of an adequate supply of islet cells throughout pancreas ontogeny by preventing exocrine cell differentiation of multipotent pancreatic progenitors [8].
  • We identified Prox1, a critical regulator of lymphangiogenesis, as a downstream target for Fiaf signaling in the intestinal lymphatic endothelium [9].
  • Voluntary wheel running of mice in pregnancy and lactation led to a twofold increase in hippocampal precursor-cell proliferation and in the number of Prox1-expressing lineage-determined cells at postnatal day 8 (P8) [10].

Anatomical context of Prox1

  • Within the vascular system, the mucin-type transmembrane glycoprotein T1alpha/podoplanin is predominantly expressed by lymphatic endothelium, and recent studies have shown that it is regulated by the lymphatic-specific homeobox gene Prox1 [11].
  • 5. Conversely, the lack of Prox1 activity substantially decreased the formation of islet cell precursors after E13.5, during a period known as the "secondary transition". Notably, this defect occurred concurrently with an abnormal increment of exocrine cells [8].
  • This finding indicates that Prox1 is one of the earliest specific markers of this commonly fated region of the mammalian endoderm [12].
  • At 0.5 day after birth, when taste cells have not yet differentiated, the expressions of Shh and Prox1 completely overlapped in the epithelium of circumvallate papillae [13].
  • Expression of lymphatic-specific markers (Flt-4, LYVE-1, Prox-1) and the tight junction proteins (ZO-1) were examined by RT-PCR, immunoblotting, and fluorescent microscopy [14].

Associations of Prox1 with chemical compounds

  • Tetracycline-induced wild-type (wt) Prox1 in tumor cells inhibited transforming activity and cellular proliferation [3].
  • BrdU/CR-labeled cells were negative for GABA and GABAA1 receptor, but early on expressed granule cell marker Prox-1 [15].
  • In situ hybridization was carried out on tissue sections using digoxigenin-labeled sense and antisense RNA probes that recognize chicken Pax-6 and Prox 1 (whose sequences were already available), and chicken Chx10 (which was cloned and sequenced as part of this study) [4].
  • ENR did not cause increased cell proliferation or an increased number of BrdU-labeled type 2 cells, but both ENR and RUN resulted in more newly generated cells lacking nestin-GFP immunoreactivity and expressing Prox-1 [16].
  • Here we report that the mRNA of a homeobox gene prox1, a candidate tumor suppressor, suffers adenosine-to-inosine nucleotide conversion and loses tumor-suppressive functions in a subset of human cancers [3].
  • In mouse embryos, expression of VEGFR3 and integrin alpha9 is increased in Prox1-expressing lymphatic endothelial cells (LECs) compared with BECs [17].

Other interactions of Prox1

  • These data suggest that the rd3 mutation affects expression of the mouse Prox1 gene [1].
  • Immunoblotting for LYVE-1 and Prox-1 showed strong expression on SV-LEC and VEC, but not AEC [14].
  • Regulation of proliferation, cell fate specification and differentiation by the homeodomain proteins Prox1, Six3, and Chx10 in the developing retina [18].
  • This delay is most apparent postnatally and correlates with appropriate changes in expression of marker genes including p57(KIP2), Maf and Prox1 [19].
  • Loss of Prox1 function severely disrupted epithelial pancreas morphology and hindered pancreatic growth without affecting significantly the genesis of endocrine cells before E11 [8].

Analytical, diagnostic and therapeutic context of Prox1


  1. Characterization of the mouse Prox1 gene. Tomarev, S.I., Zinovieva, R.D., Chang, B., Hawes, N.L. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  2. Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Harvey, N.L., Srinivasan, R.S., Dillard, M.E., Johnson, N.C., Witte, M.H., Boyd, K., Sleeman, M.W., Oliver, G. Nat. Genet. (2005) [Pubmed]
  3. Loss of function of the candidate tumor suppressor prox1 by RNA mutation in human cancer cells. Takahashi, M., Yoshimoto, T., Shimoda, M., Kono, T., Koizumi, M., Yazumi, S., Shimada, Y., Doi, R., Chiba, T., Kubo, H. Neoplasia (2006) [Pubmed]
  4. Pax-6, Prox 1, and Chx10 homeobox gene expression correlates with phenotypic fate of retinal precursor cells. Belecky-Adams, T., Tomarev, S., Li, H.S., Ploder, L., McInnes, R.R., Sundin, O., Adler, R. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  5. Hepatocyte migration during liver development requires Prox1. Sosa-Pineda, B., Wigle, J.T., Oliver, G. Nat. Genet. (2000) [Pubmed]
  6. Prox1 function is required for the development of the murine lymphatic system. Wigle, J.T., Oliver, G. Cell (1999) [Pubmed]
  7. Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. Maruyama, K., Ii, M., Cursiefen, C., Jackson, D.G., Keino, H., Tomita, M., Van Rooijen, N., Takenaka, H., D'Amore, P.A., Stein-Streilein, J., Losordo, D.W., Streilein, J.W. J. Clin. Invest. (2005) [Pubmed]
  8. Prox1 activity controls pancreas morphogenesis and participates in the production of "secondary transition" pancreatic endocrine cells. Wang, J., Kilic, G., Aydin, M., Burke, Z., Oliver, G., Sosa-Pineda, B. Dev. Biol. (2005) [Pubmed]
  9. Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor. B??ckhed, F., Crawford, P.A., O'donnell, D., Gordon, J.I. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  10. Running in pregnancy transiently increases postnatal hippocampal neurogenesis in the offspring. Bick-Sander, A., Steiner, B., Wolf, S.A., Babu, H., Kempermann, G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. Schacht, V., Ramirez, M.I., Hong, Y.K., Hirakawa, S., Feng, D., Harvey, N., Williams, M., Dvorak, A.M., Dvorak, H.F., Oliver, G., Detmar, M. EMBO J. (2003) [Pubmed]
  12. Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Burke, Z., Oliver, G. Mech. Dev. (2002) [Pubmed]
  13. Co-expression pattern of Shh with Prox1 and that of Nkx2.2 with Mash1 in mouse taste bud. Miura, H., Kusakabe, Y., Kato, H., Miura-Ohnuma, J., Tagami, M., Ninomiya, Y., Hino, A. Gene Expr. Patterns (2003) [Pubmed]
  14. Isolation and Characterization of A Novel Mouse Lymphatic Endothelial Cell Line: SV-LEC. Ando, T., Jordan, P., Joh, T., Wang, Y., Jennings, M.H., Houghton, J., Alexander, J.S. Lymphatic research and biology. (2005) [Pubmed]
  15. Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice. Brandt, M.D., Jessberger, S., Steiner, B., Kronenberg, G., Reuter, K., Bick-Sander, A., von der Behrens, W., Kempermann, G. Mol. Cell. Neurosci. (2003) [Pubmed]
  16. Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. Kronenberg, G., Reuter, K., Steiner, B., Brandt, M.D., Jessberger, S., Yamaguchi, M., Kempermann, G. J. Comp. Neurol. (2003) [Pubmed]
  17. Prox1 induces lymphatic endothelial differentiation via integrin alpha9 and other signaling cascades. Mishima, K., Watabe, T., Saito, A., Yoshimatsu, Y., Imaizumi, N., Masui, S., Hirashima, M., Morisada, T., Oike, Y., Araie, M., Niwa, H., Kubo, H., Suda, T., Miyazono, K. Mol. Biol. Cell (2007) [Pubmed]
  18. Regulation of proliferation, cell fate specification and differentiation by the homeodomain proteins Prox1, Six3, and Chx10 in the developing retina. Dyer, M.A. Cell Cycle (2003) [Pubmed]
  19. Secreted FGFR3, but not FGFR1, inhibits lens fiber differentiation. Govindarajan, V., Overbeek, P.A. Development (2001) [Pubmed]
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