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The multisystemic functions of FOXD1 in development and disease

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Abstract

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.

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Funding

The present study was supported by the Universidad del Rosario (Grant CS/Genetics/ABN062-2018). Laissue’s lab is supported by the Universidad del Rosario.

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  1. Center For Research in Genetics and Genomics-CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 No. 63C-69, Bogotá, Colombia

    Paula Quintero-Ronderos & Paul Laissue

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  1. Paula Quintero-Ronderos
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Correspondence to Paul Laissue.

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Electronic supplementary material

Supplementary Fig. S1.

FOXD1 interspecific alignment (Homo sapiens and Mus musculus). An alignment with the nucleotide and amino acid sequences from human and mouse are shown. FOXD1 protein consists of 465 and 456 amino acids in mouse and human, respectively. The bold letters within the purple box indicate the conserved DBD sequence between both species. The yellow and blue boxes show the poly-Ala and poly-Pro stretches, respectively, located within the COOH-terminal domain. (PDF 263 kb)

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Quintero-Ronderos, P., Laissue, P. The multisystemic functions of FOXD1 in development and disease. J Mol Med 96, 725–739 (2018). https://doi.org/10.1007/s00109-018-1665-2

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  • DOI: https://doi.org/10.1007/s00109-018-1665-2

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