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.
Author contributions
Y.I. carried out the experiments. Y.I. and R.S. analyzed the data. Y.I. and R.S. designed experiments and interpreted results. Y.I. and R.S. wrote the paper. R.S. conceived and supervised the project.
Funding
This work was supported by Grant-in-Aid for Young Scientists (A) [18680028] and (S) [21670002] from the Japan Society for the Promotion of Science (JSPS KAKENHI); by the Uehara Memorial Foundation; the Takeda Science Foundation; and the Mitsubishi Foundation (to R.S.).
