Hypothesis note: retina → relay map read from expression (written 2026-11-03, before any run)

This note is written before the variant python examples/retinothalamic.py --map-source expression is run (no pilot run either: the variant has only been built, not grown). Its predictions are hypotheses about this simulation, not claims about biology. The outcome is appended below, dated, after the runs.

Question

In runs 1–3 of Retina → relay: a small topographic-map experiment the graded EphA-like (x) and EphB-like (y) genes are computed by express but read by nothing: the retina → relay map comes from the gains on the diagonal of B, and EphA-KO sets the x gain to 0. When the map is instead read from the expression by the expression_gradient target rule, and EphA-KO removes the gene (expression 0 in every cell), does the model give the same conclusions?

Variant (differences from run 2, everything else unchanged: seeds 0–9, genome, stages, metrics)

  • express_fate names its three genes fate, EphA, EphB; the EphA morphogen gain is 1 in every condition.

  • grow_axons retina → relay: B = 0, rules_target = ["expression_gradient"] with EphA on axis 0 and EphB on axis 1, gain 2, attraction, min-max normalisation over the projection’s source cells. Target logit per axis 4 · 2 · (e − 0.5), the same slope as B = diag(2, 2, 0) if e were the local position.

  • EphAKO: express(knockout=["EphA"]) sets the EphA column to 0 after each express_fate step. A constant gene normalises to 0.5, so the x target is the centre of the relay, as with a 0 gain in B.

The EphA level is sigmoid(−3 + 2 x) (x the local retinal position), so after min-max normalisation it is a convex, not linear, function of x (0.32 at x = 0.5); the same for EphB on y. The expression-read target is therefore a monotonic but distorted version of the B target, pushed towards the low end of each axis.

Predictions (hypotheses, in this simulation)

  • E1 (map orientation): in WT, b2KO and TTX the map keeps both axes: r_x, r_y > 0.5, positive.

  • E2 (knockout): EphAKO gives |r_x| < 0.3, with r_y within 0.1 of WT of the same variant.

  • E3 (distortion): the expression-read WT map has a higher topographic error than the B WT map of run 2 (error measured against the B target point), by more than one pooled SD; r_x and r_y stay within 0.1 of the B WT values.

  • E4 (activity): as in runs 1–3, TTX and b2KO move topographic error up and corner separation down relative to WT of the same variant, by less than one pooled SD (weak).

  • E5 (unchanged upstream): the RGC mosaic (NND/SD) is identical to run 2 for every seed and condition, since the changes act after mosaic and the fate gene does not read EphA or EphB.

Seeds and reporting

Seeds 0–9 for every condition, python examples/retinothalamic.py --cpu --seeds 10 --map-source expression, compared with run 2 (the B variant, rerun on the same commit). Mean ± SD per condition and paired differences per seed. Each prediction is reported as held / not held / weak, whatever the outcome.

Outcome (appended 2026-11-03, after the runs)

10 seeds (0–9) per condition, python examples/retinothalamic.py --cpu --seeds 10 --map-source expression, and the B variant rerun on the same commit (identical to run 2); table in Retina → relay: a small topographic-map experiment.

  • E1: held: r_x, r_y between 0.889 and 0.896 in WT, b2KO and TTX.

  • E2: held: EphAKO r_x 0.031 ± 0.074; r_y 0.890 ± 0.031 (WT 0.889 ± 0.033).

  • E3: held: WT error 0.254 ± 0.013 against 0.230 ± 0.016 with B (paired +0.023 ± 0.010, pooled SD 0.014; 10 of 10 seeds); r_x −0.015, r_y −0.022.

  • E4: held as weak: TTX error +0.0034, separation −0.005; b2KO +0.0033, −0.003 (paired means), all below one SD.

  • E5: held: the mosaic is identical to run 2 for every seed.

  • Not predicted: the corner separation is higher than with B (0.763 ± 0.078 against 0.671 ± 0.088, higher in 10 of 10 seeds).

  • Deviations from the plan: none.

Larger-seed rerun (appended 2026-11-04, after the runs; exploratory)

50 seeds (0–49) per condition, same driver as in the run-2 rerun (see the hypotheses note of 2026-11-02). Verdicts are unchanged: E1 held (r_x 0.895, r_y 0.903 in TTX), E2 held (EphA-KO r_x 0.002, |Δr_y| 0.008), E3 held (WT error higher than with B in 50 of 50 seeds, paired +0.0263 ± 0.0109, pooled SD 0.0174; r_x −0.024, r_y −0.021), E4 weak (TTX error +0.0025, separation −0.0128; β2-KO +0.0025, −0.0073), E5 held. As with B, the topographic-error shift of TTX and β2-KO is consistent within a seed (dz +1.05 and +0.97) and small against the across-seed SD (ratio 0.15).