HOXA5 protein expression and genetic fate mapping show lineage restriction in the developing musculoskeletal system

• Miriam A. Holzman ^[1] ; Jenna M. Bergmann ^[1] ; Maya Feldman ^[1] ; Kim Landry-Truchon ^[2] ; Lucie Jeannotte ^[2] ; Jennifer H. Mansfield ^[1]
  1. [1] Columbia University

     Columbia University

     Estados Unidos

     
  2. [2] Centre de Recherche sur le Cancer de l’Université Laval, Canada
• Localización: International journal of developmental biology, ISSN 0214-6282, Vol. 62, Nº. Extra 11-12, 2018 (Ejemplar dedicado a: Hox genes: past, present and future of master regulator genes), págs. 785-796
• Idioma: inglés
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• Resumen

  • HOX proteins act during development to regulate musculoskeletal morphology. HOXA5 patterns skeletal structures surrounding the cervical-thoracic transition including the vertebrae, ribs, sternum and forelimb girdle. However, the tissue types in which it acts to pattern the skeleton, and the ultimate fates of embryonic cells that activate Hoxa5 expression are unknown. A detailed characterization of HOXA5 expression by immunofluorescence was combined with Cre/LoxP genetic lineage tracing to map the fate of Hoxa5expressing cells in axial musculoskeletal tissues and in their precursors, the somites and lateral plate mesoderm. HOXA5 protein expression is dynamic and spatially restricted in derivatives of both the lateral plate mesoderm and somites, including a subset of the lateral sclerotome, suggesting a local role in regulating early skeletal patterning. HOXA5 expression persists from somite stages through late development in differentiating skeletal and connective tissues, pointing to a continuous and direct role in skeletal patterning. In contrast, HOXA5 expression is excluded from the skeletal muscle and muscle satellite cell lineages. Furthermore, the descendants of Hoxa5-expressing cells, even after HOXA5 expression has extinguished, never contribute to these lineages. Together, these findings suggest cell autonomous roles for HOXA5 in skeletal development, as well as non-cell autonomous functions in muscle through expression in surrounding connective tissues. They also support the notion that different Hoxgenes display diverse tissue specificities and locations to achieve their patterning activity.