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miR-9 and timing of neurogenesis (Coolen 2012)


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).

Chaouiya (Thieffry)

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