title: Cell-Autonomous and Non-cell-autonomous Function of Hox Genes Specify Segmental Neuroblast Identity in the Gnathal Region of the Embryonic CNS in Drosophila.
abstract: During central nervous system (CNS) development neural stem cells (Neuroblasts, NBs) have to acquire an identity appropriate to their location. In thoracic and abdominal segments of Drosophila, the expression pattern of Bithorax-Complex Hox genes is known to specify the segmental identity of NBs prior to their delamination from the neuroectoderm. Compared to the thoracic, ground state segmental units in the head region are derived to different degrees, and the precise mechanism of segmental specification of NBs in this region is still unclear. We identified and characterized a set of serially homologous NB-lineages in the gnathal segments and used one of them (NB6-4 lineage) as a model to investigate the mechanism conferring segment-specific identities to gnathal NBs. We show that NB6-4 is primarily determined by the cell-autonomous function of the Hox gene Deformed (Dfd). Interestingly, however, it also requires a non-cell-autonomous function of labial and Antennapedia that are expressed in adjacent anterior or posterior compartments. We identify the secreted molecule Amalgam (Ama) as a downstream target of the Antennapedia-Complex Hox genes labial, Dfd, Sex combs reduced and Antennapedia. In conjunction with its receptor Neurotactin (Nrt) and the effector kinase Abelson tyrosine kinase (Abl), Ama is necessary in parallel to the cell-autonomous Dfd pathway for the correct specification of the maxillary identity of NB6-4. Both pathways repress CyclinE (CycE) and loss of function of either of these pathways leads to a partial transformation (40%), whereas simultaneous mutation of both pathways leads to a complete transformation (100%) of NB6-4 segmental identity. Finally, we provide genetic evidences, that the Ama-Nrt-Abl-pathway regulates CycE expression by altering the function of the Hippo effector Yorkie in embryonic NBs. The disclosure of a non-cell-autonomous influence of Hox genes on neural stem cells provides new insight into the process of segmental patterning in the developing CNS.
authors.affiliation: Institute of Genetics, University of Mainz, Mainz, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Becker
authors.affiliation: Institute of Genetics, University of Mainz, Mainz, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Renner
authors.affiliation: Institute of Genetics, University of Mainz, Mainz, Germany.
authors.forename: Gerhard M
authors.initials: GM
authors.lastname: Technau
authors.affiliation: Institute of Genetics, University of Mainz, Mainz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Berger
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D002490:Central Nervous System / Q000196:embryology*; D019927:Cyclin E / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C476240:Ama protein, Drosophila; D019927:Cyclin E; C066676:Dfd protein, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; C066176:Nrt protein, Drosophila; D011505:Protein-Tyrosine Kinases; C506548:Abl protein, Drosophila