Reference - Detail
|Author||Inamata Y, Shirasaki R.|
|Title||Dbx1 triggers crucial molecular programs required for midline crossing by midbrain commissural axons.|
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.
|MeSH||Animals Axons / metabolism Body Patterning / genetics Body Patterning / physiology Enhancer Elements, Genetic Female Gene Expression Regulation, Developmental Gene Knockdown Techniques Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Membrane Proteins / antagonists & inhibitors Membrane Proteins / genetics Membrane Proteins / metabolism Mesencephalon / cytology Mesencephalon / embryology* Mesencephalon / metabolism* Mice Mice, Inbred ICR Mice, Transgenic Nerve Tissue Proteins / antagonists & inhibitors Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism* Neural Stem Cells / classification Neural Stem Cells / metabolism Neurogenesis / genetics Neurogenesis / physiology Pregnancy Receptors, Cell Surface Signal Transduction|
|WOS Category||DEVELOPMENTAL BIOLOGY|
|DNA material||MSM Mouse BAC (RDB04214) MSMg01-341M02|