High impact information on Foxp1

• Foxp1 is an essential transcriptional regulator of B cell development [1].
• Foxp1 regulates B cell receptor signalling in B cells, and also during DNA damage response (Mraz et al, Blood, 2014; Cerna et al, Leukemia, 2018) .
• Foxp1 bound to the Erag enhancer and was involved in controlling variable-(diversity)-joining recombination of the gene encoding immunoglobulin heavy chain in a B cell lineage-specific way [1].
• Our results identify Foxp1 as an essential participant in the transcriptional regulatory network of B lymphopoiesis [1].
• Foxp1 deficiency was associated with decreased expression of all B lineage genes in B220+ fetal liver cells as well as with a block in the transition from pro-B cell to pre-B cell involving diminished expression of recombination-activating genes 1 and 2 [1].
• Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1 [2].

Biological context of Foxp1

• Finally, we show that the integrity of this subdomain is essential for DNA binding, making Foxp1, Foxp2, and Foxp4 the first Fox proteins that require dimerization for DNA binding [3].
• Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation [4].
• Foxp1 gene expression in projection neurons of the mouse striatum [5].

Anatomical context of Foxp1

• Foxp1 protein expression is also observed in the mesenchyme and vascular endothelial cells of the lung [6].
• All three proteins are expressed in lung epithelium with Foxp1 and Foxp4 expressed in both proximal and distal airway epithelium while Foxp2 is expressed primarily in distal epithelium [6].
• Foxp2 and Foxp1 were most highly expressed in the developing and mature basal ganglia [7].
• We have recently described a new subfamily of Fox genes, Foxp1/2/4, which are transcriptional repressors and are thought to regulate important aspects of development in several tissues, including the lung, brain, thymus and heart [4].
• Here, we show that Foxp1 is expressed in the myocardium as well as the endocardium of the developing heart [4].

Other interactions of Foxp1

• At embryonic day 12.5, Foxp1 and Foxp2 are expressed in both the mucosal and epithelial layers of the intestine [8].
• Foxp1 mutant embryos have severe defects in cardiac morphogenesis, including outflow tract septation and cushion defects, a thin ventricular myocardial compact zone caused by defects in myocyte maturation and proliferation, and lack of proper ventricular septation [4].

Analytical, diagnostic and therapeutic context of Foxp1

• In the present study, we investigated the time course and localization of Foxp2 and Foxp1 mRNA and protein expression in the developing and adult mouse using in situ hybridization and immunohistochemistry [7].
• To further explore the role of Foxp1 in cardiac development, we inactivated Foxp1 through gene targeting in embryonic stem cells [4].
• In situ hybridization combined with immunohistochemistry in the striatum of adult mice revealed that Foxp1 mRNA was detected in a subset of projection neurons, not in interneurons [5].

References