title: Dbx1 triggers crucial molecular programs required for midline crossing by midbrain commissural axons.
abstract: Axon guidance by commissural neurons has been well documented, providing us with a molecular logic of how midline crossing is achieved during development. Despite these advances, knowledge of the intrinsic genetic programs is still limited and it remains obscure whether the expression of a single transcription factor is sufficient to activate transcriptional programs that ultimately enable midline crossing. Here, we show in the mouse that the homeodomain transcription factor Dbx1 is expressed by a subset of progenitor cells that give rise to commissural neurons in the dorsal midbrain. Gain- and loss-of-function analyses indicate that the expression of Dbx1 alone is sufficient and necessary to trigger midline crossing in vivo. We also show that Robo3 controls midline crossing as a crucial downstream effector of the Dbx1-activated molecular programs. Furthermore, Dbx1 suppresses the expression of the transcriptional program for ipsilateral neuron differentiation in parallel. These results suggest that a single transcription factor, Dbx1, has an essential function in assigning midline-crossing identity, thereby contributing crucially to the establishment of the wiring laterality in the developing nervous system.
authors.affiliation: Cellular and Molecular Neurobiology Laboratory, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Inamata
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shirasaki
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D058953:Neural Stem Cells / Q000145:classification / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D000097905:Roundabout Proteins
chemical_list: D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C103403:Dbx1 protein, mouse; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins
keywords: Axon guidance; Commissural neurons; Dbx1; Midline crossing; Mouse; Robo3; Transcriptional program