The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC sensory neuron type via regulation of the ceh-36 Otx gene in C. elegans.
The differentiated features of postmitotic neurons are dictated by the expression of specific transcription factors. The mechanisms by which the precise spatiotemporal expression patterns of these factors are regulated are poorly understood. In C. elegans, the ceh-36 Otx homeobox gene is expressed in the AWC sensory neurons throughout postembryonic development, and regulates terminal differentiation of this neuronal subtype. Here, we show that the HMX/NKX homeodomain protein MLS-2 regulates ceh-36 expression specifically in the AWC neurons. Consequently, the AWC neurons fail to express neuron type-specific characteristics in mls-2 mutants. mls-2 is expressed transiently in postmitotic AWC neurons, and directly initiates ceh-36 expression. CEH-36 subsequently interacts with a distinct site in its cis-regulatory sequences to maintain its own expression, and also directly regulates the expression of AWC-specific terminal differentiation genes. We also show that MLS-2 acts in additional neuron types to regulate their development and differentiation. Our analysis describes a transcription factor cascade that defines the unique postmitotic characteristics of a sensory neuron subtype, and provides insights into the spatiotemporal regulatory mechanisms that generate functional diversity in the sensory nervous system.
Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
Kyuhyung
K
Kim
Rinho
R
Kim
Piali
P
Sengupta
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D051857:Otx Transcription Factors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011984:Sensory Receptor Cells / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; C508613:MLS-2 protein, C elegans; D051857:Otx Transcription Factors; D014157:Transcription Factors; C485328:ceh-36 protein, C elegans