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

Baruch Haimson, Oren Meir, Reut Sudakevitz-Merzbach, Gerard Elberg, Samantha Friedrich, Peter V. Lovell, Sonia Paixao, Rüdiger Klein, Claudio V. Mello, Avihu Klar

Research output: Contribution to journalArticlepeer-review


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 galliforms. The morphology and wiring at brachial levels of the chicken embryonic spinal cord resemble those of ephrin-B3 null mice. 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.

Original languageAmerican English
Article numbereabg5968
JournalScience Advances
Issue number24
StatePublished - Jun 2021

All Science Journal Classification (ASJC) codes

  • General


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