Mutations of these Hox proteins usually lead to homeotic transformation 1, 2, 3.

In most bilateral animals, the axial identity along the rostrocaudal (RC) axis of the neural tube is defined by the homeobox ( Hox) cluster genes, which encode an array of conserved homeodomain transcription factors. Our results provide a novel trans Hox-miRNA circuit filtering transcription noise and controlling the timing of protein expression to confer robust individual MN identity. Finally, we identify mir-27 as a major regulator coordinating the temporal delay and spatial boundary of Hox protein expression.

Here we uncover, using in silico simulation, two feed-forward Hox-miRNA loops accounting for the precocious and noisy Hoxa5 expression, as well as an ill-defined boundary phenotype in Dicer mutants. MicroRNA biogenesis impairment leads to precocious expression and propagates the noise of Hoxa5 at the protein level, resulting in an imprecise Hoxa5-Hoxc8 boundary. Although several 3′ Hox mRNAs are expressed in progenitors in a noisy manner, these Hox proteins are not expressed in the progenitors and only become detectable in postmitotic MNs. The initial rostrocaudal patterning of the neural tube leads to differential expression of Hox genes that contribute to the specification of motor neuron (MN) subtype identity.

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