Onset of ETS expression is not accelerated by premature exposure to signals from limb mesenchyme

The ETS transcription factors ER81 and PEA3 are expressed in discrete populations of sensory and motor neurons and regulate late events in neuronal development and limb innervation. Although initiation of ETS expression requires limb-derived signals, we show here that precocious axon growth into transplanted older donor limbs, which prematurely exposes neurons to limb-derived signals, does not accelerate the onset of expression of Er81 or Pea3. Similarly, neither MN-cadherin, which is reportedly regulated by ER81, nor T-cadherin is expressed precociously in neurons innervating older donor limbs. Thus, neurons must attain a particular level of differentiation to respond to inducing signals from limb. We also show that signals emanating from limb mesenchyme are sufficient to initiate Er81 and Pea3 expression in sensory and motor neurons in the absence of myogenic cells in Sp(d) mutant mice and that induction of ETS expression is unlikely to directly involve retinoid signaling from limb mesenchyme.