title: A competition mechanism for a homeotic neuron identity transformation in C. elegans.
abstract: Neuron identity transformations occur upon removal of specific regulatory factors in many different cellular contexts, thereby revealing the fundamental principle of alternative cell identity choices made during nervous system development. One common molecular interpretation of such homeotic cell identity transformations is that a regulatory factor has a dual function in activating genes defining one cellular identity and repressing genes that define an alternative identity. We provide evidence for an alternative, competition-based mechanism. We show that the MEC-3 LIM homeodomain protein can outcompete the execution of a neuropeptidergic differentiation program by direct interaction with the UNC-86/Brn3 POU homeodomain protein. MEC-3 thereby prevents UNC-86 from collaborating with the Zn finger transcription factor PAG-3/Gfi to induce peptidergic neuron identity and directs UNC-86 to induce an alternative differentiation program toward a glutamatergic neuronal identity. Homeotic control of neuronal identity programs has implications for the evolution of neuronal cell types.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Gordon
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: or38@columbia.edu.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hobert
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D050809:POU Domain Factors / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C407044:CEH-14 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D050809:POU Domain Factors; C106295:Pag-3 protein, C elegans; D014157:Transcription Factors; C072005:mec-3 protein, C elegans; C081539:unc-86 protein, C elegans