RRC ID 32639
Author Inamata Y, Shirasaki R.
Title Dbx1 triggers crucial molecular programs required for midline crossing by midbrain commissural axons.
Journal Development
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.
Volume 141(6)
Pages 1260-71
Published 2014-3-1
DOI 10.1242/dev.102327
PII dev.102327
PMID 24553291
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
IF 5.611
Times Cited 16
DNA material MSM Mouse BAC (RDB04214) MSMg01-341M02