HGNC Approved Gene Symbol: FOXP4
Cytogenetic location: 6p21.1 Genomic coordinates (GRCh38): 6:41,546,381-41,602,384 (from NCBI)
Teufel et al. (2003) cloned mouse Foxp4. The deduced protein shares structural features with other forkhead box proteins, including a central zinc finger domain and a C-terminal forkhead domain separated by a coiled-coil region. Northern blot analysis of adult mouse tissues detected several Foxp4 transcripts and variable levels of expression in most tissues examined. In situ hybridization of developing mouse embryos revealed Foxp4 expression around developing airway epithelium by embryonic day 13.5. Expression in the lung was reduced by day 15.5. Human FOXP4 expression was significantly reduced in 8 of 14 kidney tumors and in a larynx carcinoma compared with normal tissues, but it was not clearly reduced in other tumors.
Teufel et al. (2003) determined that the mouse Foxp4 gene contains 16 exons and spans more than 37 kb.
Hartz (2004) mapped the FOXP4 gene to chromosome 6p21.1 based on an alignment of the FOXP4 sequence (GenBank BC013030) with the genomic sequence. Teufel et al. (2003) mapped the mouse Foxp4 gene to mouse chromosome 17.
Li et al. (2004) generated mice deficient in Foxp4 by targeted disruption. Heterozygous embryos were fertile and exhibited no obvious defects; the majority of homozygous embryos died around embryonic day 12.5. Histologic analysis from embryonic days 8.5 to 12.5 revealed the development of 2 complete hearts in Foxp4 mutant embryos. This was apparent as early as embryonic day 8.5, when midline fusion of the bilateral cardiac primordia has normally occurred. The 2 hearts in Foxp4 mutants were positioned bilaterally, suggesting a lack of proper migration of the precardiac primordia to the midline. Foxp4 mutants exhibited grossly normal ventral morphogenesis and embryonic turning, suggesting that cardia bifida was not due to secondary defects in these processes, as has been observed in other mouse models. Upon sacrifice, each of the 2 bilateral hearts was beating at approximately the same rate as in wildtype embryos, although they were asynchronous. Proper chamber septation and left-right chamber specification was evident from expression of eHAND (602406) and dHAND (602407). Endocardial cushions were also present. All chamber-specific markers were appropriately placed, indicating that Foxp4 mutants developed 2 hearts with proper chamber formation and normal trabecular and compact myocardial development. Analysis of earlier embryos showed that Foxp4 mutants exhibited delay in anterior foregut closure and cell death-mediated loss of anterior foregut endoderm after closure. This delay did not interfere with normal formation of neural tube, limb bud, and head structures. Li et al. (2004) concluded that left-right chamber specification, cardiac looping, septation, cardiac myocyte differentiation, and endocardial cushion formation are preprogrammed in the precardiac mesoderm and do not require midline position identity or heart tube fusion.
Hartz, P. A. Personal Communication. Baltimore, Md. 9/16/2004.
Li, S., Zhou, D., Lu, M. M., Morrisey, E. E. Advanced cardiac morphogenesis does not require heart tube fusion. Science 305: 1619-1622, 2004. [PubMed: 15361625] [Full Text: https://doi.org/10.1126/science.1098674]
Teufel, A., Wong, E. A., Mukhopadhyay, M., Malik, N., Westphal, H. FoxP4, a novel forkhead transcription factor. Biochim. Biophys. Acta 1627: 147-152, 2003. [PubMed: 12818433] [Full Text: https://doi.org/10.1016/s0167-4781(03)00074-5]