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Gene Review

fezf2  -  FEZ family zinc finger 2

Danio rerio

Synonyms: Fez family zinc finger protein 2, Forebrain embryonic zinc finger-like protein 2, Foreheadin protein, SI:dZ6A2.1, SI:dZ6A2.7, ...
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Disease relevance of fezf2

  • Holoprosencephaly (HPE) is the most common structural defect of the developing forebrain in humans (1 in 250 conceptuses, 1 in 16,000 live-born infants) [1].
  • Overexpression of xArx resulted in morphological abnormalities in forebrain development, including loss of rostral midline structures, syn- or anophthalmia, dorsal displacement of the nasal organ, and ventral neural tube hyperplasia [2].

Psychiatry related information on fezf2

  • This similarity, along with its numerous advantages for developmental studies, makes the zebrafish a good model for studies of olfaction and forebrain maturation [3].

High impact information on fezf2

  • We also show that, consistent with results obtained using other methods, uncaging eng2a (which encodes the transcription factor Engrailed2a) in the head region during early development causes a severe reduction in the size of the eye and enhanced development of the midbrain and the midbrain-hindbrain boundary at the expense of the forebrain [4].
  • Widespread misexpression of both membrane-attached and secreted forms of oep rescues prechordal plate and forebrain development in mutant embryos but does not lead to the ectopic induction of these cell types in wild-type fish [5].
  • Increasing antivin doses progressively deleted posterior fates within the ectoderm, eventually resulting in the removal of all fates except forebrain and eyes [6].
  • In contrast, overexpression of activin or nodal-related factors converted ectoderm that was fated to be forebrain into more posterior ectodermal or mesendodermal fates [6].
  • Transplantation of these cells shows that they can induce forebrain-specific gene expression in more posterior regions of the neural plate [7].

Biological context of fezf2

  • The development of vertebrate basal forebrain dopaminergic (DA) neurons requires the conserved zinc finger protein Too Few (Tof/Fezl) in zebrafish [8].
  • Comparative synteny cloning of zebrafish you-too: mutations in the Hedgehog target gli2 affect ventral forebrain patterning [9].
  • The deletion is due to a nonautonomous action of the mutation: very few wild-type cells transplanted to the midline of a mutant embryo can rescue the forebrain phenotype, including cyclopia [10].
  • Three major axon pathways cross the midline of the vertebrate forebrain early in embryonic development: the postoptic commissure (POC), the anterior commissure (AC) and the optic nerve [11].
  • Our analysis reveals new roles for Ihx2 in midline axon guidance, forebrain patterning and eye morphogenesis [12].

Anatomical context of fezf2


Associations of fezf2 with chemical compounds


Regulatory relationships of fezf2


Other interactions of fezf2

  • The expression in the ventral forebrain was eliminated in the one-eyed pinhead mutant and the antivin RNA-injected embryos, which lack the prechordal plate [25].
  • Complex spatiotemporal expression patterns of fgf3 and fgf8 within the developing zebrafish forebrain suggest their involvement in its regionalisation and early development [26].
  • During somitogenesis, ndr2 is expressed asymmetrically in the lateral plate as are nodal-related genes of other organisms, and in a small domain in the left diencephalon, providing the first observation of asymmetric gene expression in the embryonic forebrain [27].
  • We conclude that regulated expression of zebrafish rx1 and rx2 helps to define the region of the forebrain fated to give rise to retinal tissue and may be involved in the cellular migrations that lead to splitting of the retinal field and formation of the optic primordia [28].
  • We find expression of meis2.1 in the developing zebrafish hindbrain and somites, correlating with reported sites of zebrafish hox gene expression, as well as in presumptive cerebellum, midbrain, retina and ventral forebrain [29].

Analytical, diagnostic and therapeutic context of fezf2


  1. Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination. Gripp, K.W., Wotton, D., Edwards, M.C., Roessler, E., Ades, L., Meinecke, P., Richieri-Costa, A., Zackai, E.H., Massagué, J., Muenke, M., Elledge, S.J. Nat. Genet. (2000) [Pubmed]
  2. Xenopus aristaless-related homeobox (xARX) gene product functions as both a transcriptional activator and repressor in forebrain development. Seufert, D.W., Prescott, N.L., El-Hodiri, H.M. Dev. Dyn. (2005) [Pubmed]
  3. Organization of the olfactory system in the adult zebrafish: histological, immunohistochemical, and quantitative analysis. Byrd, C.A., Brunjes, P.C. J. Comp. Neurol. (1995) [Pubmed]
  4. Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos. Ando, H., Furuta, T., Tsien, R.Y., Okamoto, H. Nat. Genet. (2001) [Pubmed]
  5. Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation. Zhang, J., Talbot, W.S., Schier, A.F. Cell (1998) [Pubmed]
  6. Activin- and Nodal-related factors control antero-posterior patterning of the zebrafish embryo. Thisse, B., Wright, C.V., Thisse, C. Nature (2000) [Pubmed]
  7. A small population of anterior cells patterns the forebrain during zebrafish gastrulation. Houart, C., Westerfield, M., Wilson, S.W. Nature (1998) [Pubmed]
  8. Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Fezl. Jeong, J.Y., Einhorn, Z., Mercurio, S., Lee, S., Lau, B., Mione, M., Wilson, S.W., Guo, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Comparative synteny cloning of zebrafish you-too: mutations in the Hedgehog target gli2 affect ventral forebrain patterning. Karlstrom, R.O., Talbot, W.S., Schier, A.F. Genes Dev. (1999) [Pubmed]
  10. Midline signaling in the primordium of the zebrafish anterior central nervous system. Hatta, K., Püschel, A.W., Kimmel, C.B. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  11. Hedgehog regulated Slit expression determines commissure and glial cell position in the zebrafish forebrain. Barresi, M.J., Hutson, L.D., Chien, C.B., Karlstrom, R.O. Development (2005) [Pubmed]
  12. belladonna/(Ihx2) is required for neural patterning and midline axon guidance in the zebrafish forebrain. Seth, A., Culverwell, J., Walkowicz, M., Toro, S., Rick, J.M., Neuhauss, S.C., Varga, Z.M., Karlstrom, R.O. Development (2006) [Pubmed]
  13. Patterning the zebrafish diencephalon by the conserved zinc-finger protein Fezl. Jeong, J.Y., Einhorn, Z., Mathur, P., Chen, L., Lee, S., Kawakami, K., Guo, S. Development (2007) [Pubmed]
  14. Zinc finger gene fez-like functions in the formation of subplate neurons and thalamocortical axons. Hirata, T., Suda, Y., Nakao, K., Narimatsu, M., Hirano, T., Hibi, M. Dev. Dyn. (2004) [Pubmed]
  15. Zinc finger protein too few controls the development of monoaminergic neurons. Levkowitz, G., Zeller, J., Sirotkin, H.I., French, D., Schilbach, S., Hashimoto, H., Hibi, M., Talbot, W.S., Rosenthal, A. Nat. Neurosci. (2003) [Pubmed]
  16. A zebrafish forebrain-specific zinc finger gene can induce ectopic dlx2 and dlx6 expression. Yang, Z., Liu, N., Lin, S. Dev. Biol. (2001) [Pubmed]
  17. Involvement of Pax6 and Otx2 in the forebrain-specific regulation of the vertebrate homeobox gene ANF/Hesx1. Spieler, D., Bäumer, N., Stebler, J., Köprunner, M., Reichman-Fried, M., Teichmann, U., Raz, E., Kessel, M., Wittler, L. Dev. Biol. (2004) [Pubmed]
  18. The zebrafish bHLH PAS transcriptional regulator, single-minded 1 (sim1), is required for isotocin cell development. Eaton, J.L., Glasgow, E. Dev. Dyn. (2006) [Pubmed]
  19. BrdU-, neuroD (nrd)- and Hu-studies reveal unusual non-ventricular neurogenesis in the postembryonic zebrafish forebrain. Mueller, T., Wullimann, M.F. Mech. Dev. (2002) [Pubmed]
  20. Zebrafish Dkk1 functions in forebrain specification and axial mesendoderm formation. Hashimoto, H., Itoh, M., Yamanaka, Y., Yamashita, S., Shimizu, T., Solnica-Krezel, L., Hibi, M., Hirano, T. Dev. Biol. (2000) [Pubmed]
  21. Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain. Barth, K.A., Wilson, S.W. Development (1995) [Pubmed]
  22. Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development. Heisenberg, C.P., Brennan, C., Wilson, S.W. Development (1999) [Pubmed]
  23. The homeobox gene mbx is involved in eye and tectum development. Kawahara, A., Chien, C.B., Dawid, I.B. Dev. Biol. (2002) [Pubmed]
  24. The zebrafish orphan nuclear receptor genes nr2e1 and nr2e3 are expressed in developing eye and forebrain. Kitambi, S.S., Hauptmann, G. Gene Expr. Patterns (2007) [Pubmed]
  25. Expression of the zinc finger gene fez-like in zebrafish forebrain. Hashimoto, H., Yabe, T., Hirata, T., Shimizu, T., Bae, Y., Yamanaka, Y., Hirano, T., Hibi, M. Mech. Dev. (2000) [Pubmed]
  26. Unique and combinatorial functions of Fgf3 and Fgf8 during zebrafish forebrain development. Walshe, J., Mason, I. Development (2003) [Pubmed]
  27. Zebrafish nodal-related genes are implicated in axial patterning and establishing left-right asymmetry. Rebagliati, M.R., Toyama, R., Fricke, C., Haffter, P., Dawid, I.B. Dev. Biol. (1998) [Pubmed]
  28. Zebrafish genes rx1 and rx2 help define the region of forebrain that gives rise to retina. Chuang, J.C., Raymond, P.A. Dev. Biol. (2001) [Pubmed]
  29. Cloning and developmental expression of a zebrafish meis2 homeobox gene. Zerucha, T., Prince, V.E. Mech. Dev. (2001) [Pubmed]
  30. Calretinin immunoreactivity in the brain of the zebrafish, Danio rerio: distribution and comparison with some neuropeptides and neurotransmitter-synthesizing enzymes. I. Olfactory organ and forebrain. Castro, A., Becerra, M., Manso, M.J., Anadón, R. J. Comp. Neurol. (2006) [Pubmed]
  31. Genetic dissection of the formation of the forebrain in Medaka, Oryzias latipes. Kitagawa, D., Watanabe, T., Saito, K., Asaka, S., Sasado, T., Morinaga, C., Suwa, H., Niwa, K., Yasuoka, A., Deguchi, T., Yoda, H., Hirose, Y., Henrich, T., Iwanami, N., Kunimatsu, S., Osakada, M., Winkler, C., Elmasri, H., Wittbrodt, J., Loosli, F., Quiring, R., Carl, M., Grabher, C., Winkler, S., Del Bene, F., Momoi, A., Katada, T., Nishina, H., Kondoh, H., Furutani-Seiki, M. Mech. Dev. (2004) [Pubmed]
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