Dbx1 triggers crucial molecular programs required for midline crossing by midbrain commissural axons
| Autor: | Yasuyuki Inamata, Ryuichi Shirasaki |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Neurogenesis
Mice Transgenic Nerve Tissue Proteins Receptors Cell Surface Biology Midbrain Mice Neural Stem Cells Mesencephalon Pregnancy Animals Molecular Biology Transcription factor Body Patterning Genetics Homeodomain Proteins Mice Inbred ICR Effector Gene Expression Regulation Developmental Membrane Proteins Commissure Axons Enhancer Elements Genetic Gene Knockdown Techniques Neuron differentiation Homeobox DBX1 Axon guidance Female Neuroscience Developmental Biology Signal Transduction |
| Zdroj: | Development (Cambridge, England). 141(6) |
| ISSN: | 1477-9129 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|