Pivotal role of hmx2 and hmx3 in zebrafish inner ear and lateral line development. 2010

Yi Feng, and Qiling Xu
Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.

hmx2 (nkx5.2) and hmx3 (nkx5.1) are highly conserved homeobox transcription factors required for mouse inner ear development. We have identified four hmx genes that are expressed in developing mechanosensory organs in zebrafish. Knockdown of both hmx2 and hmx3 disrupts formation of the mechanosensory neuromasts and also leads to impaired vestibular function in which utricular maculae fail to develop and the utricular otolith gradually fuses with the saccular otolith. We demonstrate that pax5, known to be required for development of the utricular maculae, is expressed downstream of hmx2 and hmx3. In addition, we show that FGF signaling regulates expression of hmx2 and hmx3 in the otic vesicle, and conversely, hmx2 and hmx3 maintain the expression of fgf ligands, thus revealing a novel tissue-specific feedback mechanism. Our data suggest that hmx2 and hmx3 act as cell autonomous factors required redundantly for cell fate specification and differentiation during inner ear and lateral line development.

UI MeSH Term Description Entries
D007758 Ear, Inner The essential part of the hearing organ consists of two labyrinthine compartments: the bony labyrinthine and the membranous labyrinth. The bony labyrinth is a complex of three interconnecting cavities or spaces (COCHLEA; VESTIBULAR LABYRINTH; and SEMICIRCULAR CANALS) in the TEMPORAL BONE. Within the bony labyrinth lies the membranous labyrinth which is a complex of sacs and tubules (COCHLEAR DUCT; SACCULE AND UTRICLE; and SEMICIRCULAR DUCTS) forming a continuous space enclosed by EPITHELIUM and connective tissue. These spaces are filled with LABYRINTHINE FLUIDS of various compositions. Labyrinth,Bony Labyrinth,Ear, Internal,Inner Ear,Membranous Labyrinth,Bony Labyrinths,Ears, Inner,Ears, Internal,Inner Ears,Internal Ear,Internal Ears,Labyrinth, Bony,Labyrinth, Membranous,Labyrinths,Labyrinths, Bony,Labyrinths, Membranous,Membranous Labyrinths
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004625 Embryo, Nonmammalian The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO. Embryonic Structures, Nonmammalian,Embryo, Non-Mammalian,Embryonic Structures, Non-Mammalian,Nonmammalian Embryo,Nonmammalian Embryo Structures,Nonmammalian Embryonic Structures,Embryo Structure, Nonmammalian,Embryo Structures, Nonmammalian,Embryo, Non Mammalian,Embryonic Structure, Non-Mammalian,Embryonic Structure, Nonmammalian,Embryonic Structures, Non Mammalian,Embryos, Non-Mammalian,Embryos, Nonmammalian,Non-Mammalian Embryo,Non-Mammalian Embryonic Structure,Non-Mammalian Embryonic Structures,Non-Mammalian Embryos,Nonmammalian Embryo Structure,Nonmammalian Embryonic Structure,Nonmammalian Embryos,Structure, Non-Mammalian Embryonic,Structure, Nonmammalian Embryo,Structure, Nonmammalian Embryonic,Structures, Non-Mammalian Embryonic,Structures, Nonmammalian Embryo,Structures, Nonmammalian Embryonic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D014722 Vestibule, Labyrinth An oval, bony chamber of the inner ear, part of the bony labyrinth. It is continuous with bony COCHLEA anteriorly, and SEMICIRCULAR CANALS posteriorly. The vestibule contains two communicating sacs (utricle and saccule) of the balancing apparatus. The oval window on its lateral wall is occupied by the base of the STAPES of the MIDDLE EAR. Vestibular Apparatus,Ear Vestibule,Vestibular Labyrinth,Vestibule of Ear,Vestibulum Auris,Apparatus, Vestibular,Ear Vestibules,Labyrinth Vestibule,Labyrinth Vestibules,Labyrinth, Vestibular,Labyrinths, Vestibular,Vestibular Labyrinths,Vestibule, Ear,Vestibules, Ear,Vestibules, Labyrinth
D015027 Zebrafish An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research. Brachydanio rerio,Danio rerio,B. rerio,D. rerio,Zebra Fish,Zebra Fishes,Zebra danio,Zebrafishes,D. rerios,Fishes, Zebra,Zebra danios,danio, Zebra
D051757 PAX5 Transcription Factor A paired box transcription factor that is essential for CELL DIFFERENTIATION of B-LYMPHOCYTES. It functions both as a transcriptional activator and repressor to mediate B-cell commitment. B-Cell-Specific Activator Protein,B Cell-Specific Transcription Factor,Early B Cell-Specific Binding Protein-1,Paired Box 5 Protein,Pax5A Transcription Factor,Transcription Factor PAX5,B Cell Specific Activator Protein,B Cell Specific Transcription Factor,Early B Cell Specific Binding Protein 1,PAX5, Transcription Factor,Transcription Factor, PAX5,Transcription Factor, Pax5A
D017950 Ganglia, Sensory Clusters of neurons in the somatic peripheral nervous system which contain the cell bodies of sensory nerve axons. Sensory ganglia may also have intrinsic interneurons and non-neuronal supporting cells. Sensory Ganglia,Ganglion, Sensory,Sensory Ganglion
D018398 Homeodomain Proteins Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL). Homeo Domain Protein,Homeobox Protein,Homeobox Proteins,Homeodomain Protein,Homeoprotein,Homeoproteins,Homeotic Protein,Homeo Domain Proteins,Homeotic Proteins,Domain Protein, Homeo,Protein, Homeo Domain,Protein, Homeobox,Protein, Homeodomain,Protein, Homeotic,Proteins, Homeo Domain,Proteins, Homeobox,Proteins, Homeodomain,Proteins, Homeotic

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