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Publication : Hoxa1 lineage tracing indicates a direct role for Hoxa1 in the development of the inner ear, the heart, and the third rhombomere.

First Author  Makki N Year  2010
Journal  Dev Biol Volume  341
Issue  2 Pages  499-509
PubMed ID  20171203 Mgi Jnum  J:160496
Mgi Id  MGI:4454525 Doi  10.1016/j.ydbio.2010.02.014
Citation  Makki N, et al. (2010) Hoxa1 lineage tracing indicates a direct role for Hoxa1 in the development of the inner ear, the heart, and the third rhombomere. Dev Biol 341(2):499-509
abstractText  Loss of Hoxa1 function results in severe defects of the brainstem, inner ear, and cranial ganglia in humans and mice as well as cardiovascular abnormalities in humans. Because Hoxa1 is expressed very transiently during an early embryonic stage, it has been difficult to determine whether Hoxa1 plays a direct role in the precursors of the affected organs or if all defects result from indirect effects due to mispatterning of the hindbrain. In this study we use a Hoxa1-IRES-Cre mouse to genetically label the early Hoxa1-expressing cells and determine their contribution to each of the affected organs, allowing us to conclude in which precursor tissue Hoxa1 is expressed. We found Hoxa1 lineage-labeled cells in all tissues expected to be derived from the Hoxa1 domain, such as the facial and abducens nuclei and nerves as well as r4 neural crest cells. In addition, we detected the lineage in derivatives that were not thought to have expressed Hoxa1 during development. In the brainstem, the anterior border of the lineage was found to be in r3, which is more anterior than previously reported. We also observed an interesting pattern of the lineage in the inner ear, namely a strong contribution to the otic epithelium with the exception of sensory patches. Moreover, lineage-labeled cells were detected in the atria and outflow tract of the developing heart. In conclusion, Hoxa1 lineage tracing uncovered new domains of Hoxa1 expression in rhombomere 3, the otic epithelium, and cardiac precursors, suggesting a more direct role for Hoxa1 in development of these tissues than previously believed.
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