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RESEARCH PAPER

Hoxb1 functions in both motoneurons and in tissues of the periphery to establish and maintain the proper neuronal circuitry

Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84112, USA

Formation of neuronal circuits in the head requires the coordinated development of neurons within the central nervous system (CNS) and neural crest-derived peripheral target tissues. Hoxb1, which is expressed throughout rhombomere 4 (r4), has been shown to be required for the specification of facial branchiomotor neuron progenitors that are programmed to innervate the muscles of facial expression. In this study, we have uncovered additional roles for Hoxb1-expressing cells in the formation and maintenance of the VIIth cranial nerve circuitry. By conditionally deleting the Hoxb1 locus in neural crest, we demonstrate that Hoxb1 is also required in r4-derived neural crest to facilitate and maintain formation of the VIIth nerve circuitry. Genetic lineage analysis revealed that a significant population of r4-derived neural crest is fated to generate glia that myelinate the VIIth cranial nerve. Neural crest cultures show that the absence of Hoxb1 function does not appear to affect overall glial progenitor specification, suggesting that a later glial function is critical for maintenance of the VIIth nerve. Taken together, these results suggest that the molecular program governing the development and maintenance of the VIIth cranial nerve is dependent upon Hoxb1, both in the neural crest-derived glia and in the facial branchiomotor neurons.

[Keywords: Neural crest; hoxb1; glia; Cre/loxP; hindbrain; rhombomere]

Received March 26, 2004; revised version accepted May 4, 2004.

¹ Corresponding author. E-MAIL mario.capecchi{at}genetics.utah.edu; FAX (801) 585-3425.

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