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Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

By Baruch Haimson, Oren Meir, Reut Sudakevitz-Merzbach, Gerard Elberg, Samantha Friedrich, peter Lovell, sonia Paixao, Reudiger Klen, Claudio V. Mello, Avihu Klar

Posted 29 Jan 2021
bioRxiv DOI: 10.1101/2021.01.29.428748

Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avian ephrin-B3 gene lacks an enhancer that drives midline expression, and is missing in Galliformes. The morphology and wiring at brachial levels of the chick spinal cord resemble those of ephrin-B3 null mice. Importantly, dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level, and is prevented by expression of exogenous ephrin-B3 at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping.

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