Meta-Biol

• Pathways

Commissural axons project to the floor plate, attracted by the interaction of their DCC receptors with Netrin-1 (NTN1) produced by floor plate cells (Dickson and Gilestro 2006) and radial glia (Dominici et al. 2017, Varadarajan et al. 2017). Once an axon enters the floor plate, it must be efficiently expelled on the contralateral side. A switch from attraction to repulsion allows commissural axons to enter and then leave the CNS midline. Based on studies in Xenopus neurons and by yeast two hybrid screens, it is observed that the attractive response of axons to netrins is silenced by activation of ROBO. SLIT bound ROBO binds to DCC, preventing it from transducing an attractive response to netrin. The sensitivity of axons to the repulsive action of SLIT does not only depend on repulsive SLIT receptors (ROBO1 and ROBO2), but is also influenced by expression of ROBO3, a SLIT receptor that suppresses the activity of ROBO1 and ROBO2. Upon crossing the midline, commissural axons downregulate expression of ROBO3 and increase expression of ROBO1/ROBO2 (reviewed by Dickson and Gilestro, 2006). Two transcript variants of ROBO3, ROBO3.1 and ROBO3.2 are considered to play different roles in midline crossing. ROBO3.1 is expressed in the pre-crossing and crossing commissural axons, while ROBO3.2, generated by alternative splicing, is expressed after midline crossing and thought to block midline re-crossing (Chen et al. 2008). In addition to SLITs, a secreted ligand NELL2 also acts as an axonal guidance cue that, by acting through ROBO3 receptors, helps to steer commissural axons to the midline. Both ROBO3.1 and ROBO3.2 can bind to a secreted ligand NELL2. Pre-crossing commissural axons, which express ROBO3.1, are repelled by NELL2. Post-crossing axons, which express ROBO3.2 are not repelled by NELL2 (Jaworski et al. 2015). .

Neurogenesis is the process by which neural stem cells give rise to neurons, and occurs both during embryonic and perinatal development as well as in specific brain lineages during adult life (reviewed in Gotz and Huttner, 2005; Yao et al, 2016; Kriegstein and Alvarez-Buylla, 2009).

As early steps towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of several processes have been annotated. Aspects of processes involved in most developmental processes, transcriptional regulation of pluripotent stem cells, gastrulation, and activation of HOX genes during differentiation are annotated. More specialized processes include nervous system development , aspects of the roles of cell adhesion molecules in axonal guidance and myogenesis, transcriptional regulation in pancreatic beta cell, cardiogenesis, transcriptional regulation of granulopoeisis, transcriptional regulation of testis differentiation, transcriptional regulation of white adipocyte differentiation, and molecular events of "nodal" signaling, LGI-ADAM interactions, and keratinization.