Disease relevance of Foxd3

• Extensive Northern analysis of Genesis found that the message was exclusively expressed in embryonic stem cells or their malignant equivalent, embryonal carcinoma cells [1].
• Based on that finding, Genesis was retrovirally transduced into pluripotent N-Tera-2 clone D1 (NT2/D1) teratocarcinoma cells, which are a well-described in vitro model of neural development [2].

High impact information on Foxd3

• These results establish Foxd3 as a factor required for the maintenance of progenitor cells in the mammalian embryo [3].
• Together these results suggest Foxd3 can function independently of Slug and RhoB to promote the development of neural crest cells from neural tube progenitors [4].
• We show that misexpression of Foxd3 in the chick neural tube promotes a neural crest-like phenotype and suppresses interneuron differentiation [4].
• We previously showed, using differential expression screening and in situ hybridization that Vanin-1, which encodes a glycosylphosphatidylinositol-linked membrane-associated pantetheinase, is expressed in a sex-specific manner during fetal gonad development in mice (Bowles, J., Bullejos, M., and Koopman, P. (2000) Genesis 27, 124-135) [5].
• DNA sequences that Genesis protein would interact with were characterized and were found to contain a consensus similar to that found in an embryonic stem cell enhancer sequence [1].

Biological context of Foxd3

• Re-expression of the ES-specific gene Foxd3 from somatic-derived chromosomes suggested that the somatic nucleus had been reprogrammed [6].
• In this study in situ cRNA hybridization experiments revealed that Genesis was expressed during embryogenesis only in developing neural crest cells [2].

Anatomical context of Foxd3

• Here, we demonstrate that Foxd3 is also required in the trophoblast lineage [7].
• Trophoblast progenitors in Foxd3-/- embryos do not self-renew and are not multipotent, but instead give rise to an excess of trophoblast giant cells [7].
• Foxd3 is expressed in most beta cells and infrequently in alpha and PP cells but is not expressed in somatostatin cells [8].
• To explore that possibility in a heterologous system of differentiation, Genesis was stably transduced into the IL-3-dependent myeloid cell line 32D using a retroviral expression vector [9].
• The winged helix transcription factor Hfh2 is expressed in neural crest and spinal cord during mouse development [10].

Associations of Foxd3 with chemical compounds

• Although RA-induced expression of neuronal differentiation markers was not influenced by forced overexpression of Genesis in NT2-D1 cells, proliferation of Genesis-transduced cells continued following RA treatment [2].
• A novel repressor of the Winged Helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis (also called HFH2), was previously found to be exclusively expressed in primitive embryonic cell lines [2].

Other interactions of Foxd3

• Expression and shifting subcellular localization of the transcription factor, Foxd3, in embryonic and adult pancreas [8].
• Therefore, Genesis may play a role in the regulation of primitive neural crest development by preventing terminal quiescence through inhibition of p21 protein expression [2].
• Maturation of bone marrow lymphocytes. III. Genesis of Fc receptor-bearing "null" cells and B lymphocytes subtypes defined by concomitant expression of surface IgM, Fc, and complement receptors [11].

Analytical, diagnostic and therapeutic context of Foxd3

• The subcellular localization of Foxd3 varies with fat content in the diet; with a high fat diet the protein is found primarily in the cytoplasm while a low fat diet results in nuclear localization [8].

References