High impact information on Hmx3

• Hmx2, a member of the Hmx homeobox gene family, is coexpressed with Hmx3 in the dorsolateral otic epithelium [1].
• Inner ear and maternal reproductive defects in mice lacking the Hmx3 homeobox gene [2].
• Hmx3 null females can be fertilized and their embryos undergo normal preimplantation development, but the embryos fail to implant successfully in the Hmx3 null uterus and subsequently die [2].
• Both the sensory and secretory epithelium of the cochlear duct appear normal in the Hmx3 null animals [2].
• Hmx3 is one of the earliest markers for vestibular inner ear development during embryogenesis, and is also upregulated in the myometrium of the uterus during pregnancy [2].

Biological context of Hmx3

• Assignment of the murine Hmx2 and Hmx3 homeobox genes to the distal region of mouse chromosome 7 [3].
• The mouse Nkx-5.1 and Nkx-5.2 genes have been identified by sequence homology to Drosophila NK genes within the homeobox domain [4].
• A similar consensus binding sequence was isolated for both Nkx5 proteins using binding site selection [5].
• Analysis of the Fam3c promoter region demonstrated a putative Nkx5.1 binding site [6].
• Based on our findings, we hypothesize that Fam3c may be a downstream target gene for the Nkx5.1 transcription factor, and may thus be involved in cell differentiation and proliferation during inner ear embryogenesis [6].

Anatomical context of Hmx3

• Both Hmx2 and Hmx3 transcripts are coexpressed in the developing central nervous system including the neural tube and hypothalamus [1].
• Transfer of preimplantation embryos from mutant Hmx3 uterine horns to wild-type pseudopregnant females results in successful pregnancy, indicating a failure of the Hmx3 null uterus to support normal post-implantation pregnancy [2].
• During evolution, mouse Hmx2 and Hmx3 may have retained a primary function in central nervous system development as suggested by their expression in the postmitotic cells of the neural tube, as well as in the hypothalamus, the mesencephalon, metencephalon and discrete regions in the myelencephalon during embryogenesis [7].
• However, null mutation of the Hmx3 patterning gene produced only a limited vestibular defect, and did not result in the agenesis of the vestibule [8].
• The balance defect correlates with severe malformations of the vestibular organ in Nkx5-1(-/-) mutants, which fail to develop the semicircular canals [9].

Co-localisations of Hmx3

• Nkx-5.2 transcripts are first detected in E13.5 embryos where they colocalize with Nkx-5.1 mRNA in the developing central nervous system and the inner ear [4].

Regulatory relationships of Hmx3

• Pax2 is expressed in epithelial cells of the ventral part of the membranous labyrinth where it overlaps with the Nkx5 expression domain. sek shows a complementary pattern to Nkx5 in the vestibular epithelium [10].

Other interactions of Hmx3

• The Igf1r and Agc1 loci are syntenic on mouse Chr 7, together with Hmx3, an H6-like locus [11].
• These data suggest that Nkx5 genes, Pax2 and sek play different roles in the patterning of inner ear structures [10].
• Mice carrying the Nkx5-1 null mutation exhibit behavioural abnormalities that resemble the typical hyperactivity and circling movements of the shaker/waltzer type mutants [9].

References