title: A dimerized HMX1 inhibits EPHA6/epha4b in mouse and zebrafish retinas.
abstract: HMX1 is a homeobox-containing transcription factor implicated in eye development and responsible for the oculo-auricular syndrome of Schorderet-Munier-Franceschetti. HMX1 is composed of two exons with three conserved domains in exon 2, a homeobox and two domains called SD1 and SD2. The function of the latter two domains remains unknown. During retinal development, HMX1 is expressed in a polarized manner and thus seems to play a role in the establishment of retinal polarity although its exact role and mode of action in eye development are unknown. Here, we demonstrated that HMX1 dimerized and that the SD1 and homeodomains are required for this function. In addition, we showed that proper nuclear localization requires the presence of the homeodomain. We also identified that EPHA6, a gene implicated in retinal axon guidance, is one of its targets in eye development and showed that a dimerized HMX1 is needed to inhibit EPHA6 expression.
authors.affiliation: IRO - Institute for Research in Ophthalmology, Sion, Switzerland; Faculty of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Marcelli
authors.affiliation: IRO - Institute for Research in Ophthalmology, Sion, Switzerland.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Boisset
authors.affiliation: IRO - Institute for Research in Ophthalmology, Sion, Switzerland; Faculty of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland; Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D036122:Receptor, EphA4 / Q000378:metabolism*; D036124:Receptor, EphA6 / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D050505:Mutant Proteins; C529125:NKX5-3 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D036122:Receptor, EphA4; D036124:Receptor, EphA6