The multisystemic functions of FOXD1 in development and disease

Transcription factors (TFs) participate in a wide range of cellular processes due to their inherent function as essential regulatory proteins. Their dysfunction has been linked to numerous human diseases. The forkhead box (FOX) family of TFs belongs to the “winged helix” superfamily, consisting of proteins sharing a related winged helix-turn-helix DNA-binding motif. FOX genes have been extensively present during vertebrates and invertebrates’ evolution, participating in numerous molecular cascades and biological functions, such as embryonic development and organogenesis, cell cycle regulation, metabolism control, stem cell niche maintenance, signal transduction, and many others. FOXD1, a forkhead TF, has been related to different key biological processes such as kidney and retina development and embryo implantation. FOXD1 dysfunction has been linked to different pathologies, thereby constituting a diagnostic biomarker and a promising target for future therapies. This paper aims to present, for the first time, a comprehensive review of FOXD1’s role in mouse development and human disease. Molecular, structural, and functional aspects of FOXD1 are presented in light of physiological and pathogenic conditions, including its role in human disease aetiology, such as cancer and recurrent pregnancy loss. Taken together, the information given here should enable a better understanding of FOXD1 function for basic science researchers and clinicians.