Alternative titles; symbols
HGNC Approved Gene Symbol: FOXB1
Cytogenetic location: 15q22.2 Genomic coordinates (GRCh38): 15:60,004,311-60,007,444 (from NCBI)
FOXB1 is a winged helix gene encoding a transcription factor (Labosky et al., 1997).
Kaestner et al. (1993) cloned mouse Foxb1, also known as Fkh5, which shares a high degree of similarity with the Drosophila forkhead gene. Fkh5 was expressed during mouse embryogenesis and in adult brain and thymus.
Kaestner et al. (1996) cloned the cDNA of mouse Fkh5, which encodes a protein of 324 amino acids and a calculated molecular mass of 34.9 kD. Fkh5 contains a class IV winged helix domain; from the N terminus to the winged helix domain is a very short domain of only 10 amino acids. RNase protection analysis detected expression of Fkh5 only in hypothalamus of adult mouse brain. In situ hybridization of mouse embryos indicated expression of Fkh5 in the developing diencephalon from the headfold stage onward.
Using in situ hybridization Labosky et al. (1997) showed that expression of Fkh5, also known as Mf3, was restricted to the presomitic mesoderm and anterior neurectoderm and mesoderm in early mouse embryos. By 9.5 days postcoitum, expression in the nervous system was predominantly in the diencephalon, midbrain, and neural tube. After midgestation, the highest level of expression was in the mammillary bodies, the posteriormost part of the hypothalamus.
Kaestner et al. (1996) determined that mouse Fkh5 gene consists of 2 exons.
Stumpf (2022) mapped the FOXB1 gene to chromosome 15q22.2 based on an alignment of the FOXB1 sequence (GenBank AK290944) with the genomic sequence (GRCh38).
Using linkage analysis, Kaestner et al. (1996) mapped the Fkh5 gene to mouse chromosome 9.
By analyzing a mouse line carrying a replacement of the Foxb1 locus with an EGFP reporter, Zhang et al. (2017) showed that Foxb1 was expressed in oligodendrocyte-generating regions of the embryonic medulla oblongata (hindbrain) and the thalamus (forebrain). Foxb1-expressing neural progenitor cells (NPCs) produced some neurons and few astrocytes but mostly oligodendrocytes (OLs), including oligodendrocyte precursor cells (OPCs). Foxb1 deficiency in NPCs resulted in generation of an abnormally large number of OPCs and immature OL to the detriment of neurons, astrocytes, and mature OLs. Foxb1 inactivation increased the proliferation of OPC. However, electron microscopic analysis showed that the axonal G-ratio was not changed in Foxb1-deficient hindbrain. These results indicated that Foxb1 negatively regulates the proliferation of oligodendrocyte progenitors in restricted regions of mouse brain.
Labosky et al. (1997) found that most Mf3 -/- mouse embryos were morphologically and histologically normal throughout gestation. However, 11% of Mf3 -/- embryos displayed abnormalities and died in utero, with approximately 6% showing an open neural tube in the diencephalon and midbrain region and 5% showing a severe reduction of the posterior body axis. At birth, Mf3 -/- mice had no gross external anatomic differences compared to control, but showed growth retardation as early as 2 to 3 days after birth, and approximately one-third of the animals died before weaning. Growth was normal for those who survived past weaning. This growth retardation was not a direct result of lack of circulating growth hormone or thyrotropin. Mf3 -/- mice also exhibited abnormal hindlimb clasping behavior. Although small, the surviving Mf3 -/- mice were healthy and fertile and lived to over 1 year of age. However, Mf3 -/- mothers were unable to release milk in response to suckling of their pups. This nursing defect could be corrected with intraperitoneal injections of oxytocin. Studies showed that there was no inherent defect in the secretion of oxytocin into the bloodstream of Mf3 -/- mothers, leading Labosky et al. (1997) to conclude that the oxytocin surge necessary to induce milk ejection was either not generated or was not of sufficient amplitude to be functional.
Kaestner, K. H., Lee, K. H., Schlondorff, J., Hiemisch, H., Monaghan, A. P., Schutz, G. Six members of the mouse forkhead gene family are developmentally regulated. Proc. Nat. Acad. Sci. 90: 7628-7631, 1993. [PubMed: 7689224] [Full Text: https://doi.org/10.1073/pnas.90.16.7628]
Kaestner, K. H., Schutz, G., Monaghan, A. P. Expression of the winged helix genes fkh-4 and fkh-5 defines domains in the central nervous system. Mech. Dev. 55: 221-230, 1996. [PubMed: 8861101] [Full Text: https://doi.org/10.1016/0925-4773(96)00507-2]
Labosky, P. A., Winnier, G. E., Jetton, T. L., Hargett, L., Ryan, A. K., Rosenfeld, M. G., Parlow, A. F., Hogan, B. L. The winged helix gene, Mf3, is required for normal development of the diencephalon and midbrain, postnatal growth and the milk-ejection reflex. Development 124: 1263-1274, 1997. [PubMed: 9118797] [Full Text: https://doi.org/10.1242/dev.124.7.1263]
Stumpf, A. M. Personal Communication. Baltimore, Md. 07/15/2022.
Zhang, Y., Hoxha, E., Zhao, T., Zhou, X., Alvarez-Bolado, G. Foxb1 regulates negatively the proliferation of oligodendrocyte progenitors. Front. Neuroanat. 11: 53, 2017. [PubMed: 28725186] [Full Text: https://doi.org/10.3389/fnana.2017.00053]