Elsevier

Developmental Biology

Volume 344, Issue 2, 15 August 2010, Pages 857-868
Developmental Biology

Spatiotemporally restricted regulation of generic motor neuron programs by miR-196-mediated repression of Hoxb8

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Abstract

Hox transcription factors are key determinants of antero-posterior identity and have been implicated in assigning positionally appropriate neuron subtypes in the neural tube. These roles inherently necessitate stringent control mechanisms that confine Hox protein activities to discrete spatiotemporal domains. Here, we provide evidence that the timing and rostro-caudal extent of Hoxb8 activity in the neural tube is tightly regulated by miR-196, a microRNA species encoded within three Hox gene clusters. In vitro and in vivo sensor-tracer analysis and transcription assays revealed that miR-196 activity restricts the caudal extent of Hoxb8 expression to the thoracic-lumbar intersect via 3' UTR-dependent negative regulation. Spatio-temporally inappropriate Hoxb8 activity, through relief of miR-196-mediated repression or direct misexpression, affected normal progression of motor neuron genesis by affecting generic motor neuron differentiation programs. In addition to uncovering a role for microRNA-dependent restriction of caudal Hox activities, these data thus indicate novel aspects of Hox-dependent neural tube patterning by revealing a requirement of temporal regulation of a generic neuronal specification program.

Keywords

MicroRNAs
Hox genes
Motor neuron generation
Cell cycle

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1

Present address: Department of Developmental Biology, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW 2010, Australia.