Early stages of oligodendrocyte development in the embryonic murine spinal cord proceed normally in the absence of Hoxa2.

Abstract

Recent discoveries have enhanced our knowledge of the transcriptional control of oligodendrocyte (OG) development. In particular, the transcription factors (TFs) Olig2, Pax6, and Nkx2.2 have been shown to be important in the specification and/or maturation of the OG lineage. Although numerous other TFs are expressed by OGs, little is known regarding their role(s) in oligodendrogenesis. One such TF is the homeobox gene Hoxa2, which was recently shown to be expressed by O4(+) pro-oligodendrocytes. The objectives of this study were to examine the expression of Hoxa2 during the early stages of OG development, as well as to determine whether Hoxa2 is required for specification and/or early maturation of OGs. Immunocytochemical analysis of primary mixed glial cultures demonstrated that Hoxa2 was expressed throughout oligodendrogenesis, diminishing only with the acquisition of a myelinating phenotype. Serial transverse spinal cord sections from embryonic days 12.5, 14.25, 16, and 18 Hoxa2(+/+), Hoxa2(+/-), and Hoxa2(-/-) mice were subjected to single and double immunohistochemical analysis in order to examine Hoxa2, Olig2, Nkx2.2, and Pax6 expression profiles. Results obtained from Hoxa2(+/+) and Hoxa2(+/-) mice suggested that Hoxa2 was expressed by migratory oligodendroglial cells. In addition, comparison of spinal cord sections obtained from Hoxa2(+/+), Hoxa2(+/-), and Hoxa2(-/-) mice suggested that specification and early maturation of OGs proceeded normally in the absence of Hoxa2, since there were no obvious alterations in the expression patterns of Olig2, Nkx2.2, and/or Pax6. Hence, although Hoxa2 is expressed throughout OG development, it does not appear to be critical for early stages of oligodendrogenesis in the murine spinal cord.