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Key Event Title
foxi1 expression, increased
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Repression of Gbx2 expression leads to increased mortality||KeyEvent||Vid Modic (send email)||Under development: Not open for comment. Do not cite|
Key Event Description
Foxi1 exhibits DNA-binding transcription factor activity. Involved in several processes, including animal organ development; epidermal cell fate specification; and neuron development. Predicted to localize to nucleus. Is expressed in several structures, including ectoderm; epibranchial ganglion; head; neural crest; and neurogenic field. Human ortholog(s) of this gene implicated in autosomal recessive nonsyndromic deafness 4. Orthologous to human FOXI1 (forkhead box I1) (ZFIN Gene: Foxi1, n.d.). The zebrafish Foxi1 protein shares 52% identity with Xenopus FoxI1c and 40% with human FOXI1; the forkhead domains are 95% and 94% identical, respectively (Solomon et al., 2003).
Zebrafish Foxi1 is expressed in nonneural ectoderm. Based on double in situ labeling with otx2, the anterior-most region of foxi1 expression lies just posterior to the midbrain hindbrain boundary. At the three-somite stage, the two domains of foxi1 expression become more compact, but are still located in approximately the same position lateral to the hindbrain (Solomon et al., 2003).
How It Is Measured or Detected
Inhibition of expression can be measured with reverse transcription polymerase chain reaction (RT-PCR). This technique is primarily used to measure the amount of specific RNA which is achieved by monitoring the amplification reaction using fluorescence, a technique called real-time PCR or quantitative PCR (qPCR) (Wong & Medrano, 2005). Combined RT-PCR and qPCR are routinely used for analysis of gene expression.
Domain of Applicability
Foxi I class genes have been described in zebrafish (Hans et al., 2004; Solomon et al., 2003), humans (Larsson et al., 1995; Pierrou et al., 1994), mouse (Hulander et al., 1998; Overdier et al., 1997), rat (Clevidence et al., 1993) and Xenopus (Lef et al., 1994, 1996). However, it is unclear whether zebrafish foxi1 is orthologous to any one of these genes. The Xenopus FoxI1c (Lef et al., 1996), FoxI1a and FoxI1b genes (Lef et al., 1994) share the highest degree of sequence conservation with the zebrafish gene. The expression pattern of the two Xenopus pseudoallelic variants FoxI1a/b does not suggest functional similarity to zebrafish foxi1. Of the three Xenopus FoxI genes, FoxI1c (XFD-10) is most similar to foxi1 in sequence. However, Xenopus FoxI1c was reported to be expressed in the neuroectoderm and somites but not in the otic placode, unlike the pattern for foxi1 reported in (Lef et al., 1996). (Pohl et al., 2002) report provides a more detailed description of Xenopus FoxI1c, which suggests that this gene is expressed in preplacodal tissue and the branchial arches, similar to observations for zebrafish foxi1. Thus, it appears probable that Xenopus FoxI1c represents the ortholog of zebrafish foxi1 (Solomon et al., 2003).
Clevidence, D. E., Overdier, D. G., Taot, W., Qian, X., Pani, L., Lait, E., & Costa, R. H. (1993). Identification of nine tissue-specific transcription factors of the hepatocyte nuclear factor 3/forkhead DNA-binding-domain family (tissue-specific transcription factors/gene family/differentiation). In Proc. Natl. Acad. Sci. USA (Vol. 90).
Hulander, M., Wurst, W., Carlsson, P., & Enerbäck, S. (1998). The winged helix transcription factor FKh10 is required for normal development of the inner ear. Nature Genetics, 20(4), 374–376. https://doi.org/10.1038/3850
Larsson, C., Hellqvist, M., Pierrou, S., White, I., Enerback, S. and, & Carlsson, P. (1995). Chromosomal Localization of Six Human Forkhead Genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12). Genomics, 30, 464–469.
Lef, J., Clement, J. H., Oschwald, R., Köster, M., & Knöchel, W. (1994). Spatial and temporal transcription patterns of the forkhead related XFD-2/XFD-2′ genes in Xenopus laevis embryos. Mechanisms of Development, 45(2), 117–126. https://doi.org/10.1016/0925-4773(94)90025-6
Lef, J., Dege, P., Scheucher, M., Forsbach-Birk, V., Clement, J. H., & Knöchel, W. (1996). A fork head related multigene family is transcribed in Xenopus laevis embryos. International Journal of Developmental Biology, 40(1), 245–253. https://doi.org/10.1387/ijdb.8735935
Overdier, D. G., Ye, H., Peterson, R. S., Clevidence, D. E., & Costa, R. H. (1997). The Winged Helix Transcriptional Activator HFH-3 Is Expressed in the Distal Tubules of Embryonic and Adult Mouse Kidney*. In THE JOURNAL OF BIOLOGICAL CHEMISTRY (Vol. 272, Issue 21). https://doi.org/10.1074/jbc.272.21.13725
Pierrou, S., Hellqvist, M., Samuelsson, L., Enerbäck, S., & Carlsson, P. (1994). Cloning and characterization of seven human forkhead proteins: Binding site specificity and DNA bending. EMBO Journal, 13(20), 5002–5012. https://doi.org/10.1002/j.1460-2075.1994.tb06827.x
Pohl, B. S., Knöchel, S., Dillinger, K., & Knöchel, W. (2002). Sequence and expression of FoxB2 (XFD-5) and FoxI1c (XFD-10) in Xenopus embryogenesis. Mechanisms of Development, 117(1–2), 283–287. https://doi.org/10.1016/S0925-4773(02)00184-3
Solomon, K. S., Kudoh, T., Dawid, I. B., & Fritz, A. (2003). Zebrafish foxi1 mediates otic placode formation and jaw development. Development, 130(5), 929–940. https://doi.org/10.1242/dev.00308
Wong, M. L., & Medrano, J. F. (2005). Real-time PCR for mRNA quantitation. 39(1), 75–85. https://doi.org/10.2144/05391RV01
ZFIN Gene: foxi1. (n.d.). Retrieved April 12, 2021, from https://zfin.org/ZDB-GENE-030505-1