Homeobox genes and axial patterning

Antennapedia (Antp)-class homeobox genes are involved in the determination of pattern formation along the anterior-posterior axis of the animal embryo. A phylogenetic analysis of Antp-class homeodomains of the nematode, Drosophila, amphioxus, mouse, and human indicates that the 13 cognate group genes of this gene family can be divided into two major groups, i.e., groups I and II. Group I genes can further be divided into subgroups A (cognate groups 1–2), B (cognate group 3), and C (cognate groups 4–8), and group II genes can be divided into subgroups D (cognate groups 9–10) and E (cognate groups 11–13), though this classification is somewhat ambiguous. Evolutionary distances among different amino acid sequences suggest that the divergence between group I and group II genes occurred ∼1000 million years (MY) ago, and the five different subgroups were formed by ∼600 MY ago, probably before the divergence of Pseudocoelomates (e.g., nematodes) and Coelomates (e.g., insects and chordates). Our results show that the genes that are phylogenetically close are also closely located in the chromosome, suggesting that the colinearity between the gene expression and gene arrangement was generated by successive tandem gene duplications and that the gene arrangement has been maintained by some sort of selection.

Download Full-text

Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2

Cell Death and Disease ◽

10.1038/s41419-021-03801-w ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Manuel Pedro Jimenez-García ◽

Antonio Lucena-Cacace ◽

Daniel Otero-Albiol ◽

Amancio Carnero

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Transcription Factors ◽

Neural Crest ◽

Tumor Suppressors ◽

Homeobox Genes ◽

Neuronal Cell ◽

Cell Gene Expression

AbstractThe EMX (Empty Spiracles Homeobox) genes EMX1 and EMX2 are two homeodomain gene members of the EMX family of transcription factors involved in the regulation of various biological processes, such as cell proliferation, migration, and differentiation, during brain development and neural crest migration. They play a role in the specification of positional identity, the proliferation of neural stem cells, and the differentiation of certain neuronal cell phenotypes. In general, they act as transcription factors in early embryogenesis and neuroembryogenesis from metazoans to higher vertebrates. The EMX1 and EMX2’s potential as tumor suppressor genes has been suggested in some cancers. Our work showed that EMX1/EMX2 act as tumor suppressors in sarcomas by repressing the activity of stem cell regulatory genes (OCT4, SOX2, KLF4, MYC, NANOG, NES, and PROM1). EMX protein downregulation, therefore, induced the malignance and stemness of cells both in vitro and in vivo. In murine knockout (KO) models lacking Emx genes, 3MC-induced sarcomas were more aggressive and infiltrative, had a greater capacity for tumor self-renewal, and had higher stem cell gene expression and nestin expression than those in wild-type models. These results showing that EMX genes acted as stemness regulators were reproduced in different subtypes of sarcoma. Therefore, it is possible that the EMX genes could have a generalized behavior regulating proliferation of neural crest-derived progenitors. Together, these results indicate that the EMX1 and EMX2 genes negatively regulate these tumor-altering populations or cancer stem cells, acting as tumor suppressors in sarcoma.

Download Full-text