miR-9 and timing of neurogenesis (Coolen 2012)

Taxon: Zebrafish
Process: Development | Differentiation
Submitter: Chaouiya (Thieffry)

Supporting paper: Coolen, Marion and Thieffry, Denis and Drivenes, \Oyvind and Becker, Thomas S. and Bally-Cuif, Laure (2012). miR-9 Controls the Timing of Neurogenesis through the Direct Inhibition of Antagonistic Factors. Developmental Cell. 10.1016/j.devcel.2012.03.003

Model file(s)	Description(s)
zebra_miR9_22jul2011.zginml	Model file

Summary:
This Boolean model displays the subtle role of miR-9 in the course of neural specification in zebrafish.

Figure 1: Green arrows represent positive regulations, whereas red T arrows represent inhibitory interactions. Dotted lines represent suspected (but not yet molecularly characterized) direct or indirect interactions, which prevent the expression of a gene in the progenitor or neuronal precursor states, such as elavl3/HuC inhibition in progenitors.

The node P denotes a proliferating progenitor state (P=1, N=0). It is defined by the expression of Her6 and/or Zic5. The node N denotes the commitment of a progenitor into a neural precursor (P=0, N=1). By inhibiting genes with opposite effect on neural differentiation, miR-9 activity generates an ambivalent state (P=0, N=0) poised for responding to both progenitor maintenance and commitment cues.

Model simulations qualitatively recapitulate all the experimental results presented in Coolen et al (submitted), for the wild-type as well as for various mutant situations (including loss-of-functions, ectopic gene expressions, and miR-9 target protection by morpholinos).