Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm.
It is rapidly becoming accepted that the vertebrate neural tube, in particular the hindbrain, develops into a segmented structure. After segment formation, cells in the neural tube do not cross segmental boundaries, and segment-specific gene expression is observed. However, it is not known what positional cues instruct the neural tube to express genes in this restricted manner. We have cloned a murine homeobox-containing gene, Hox-2.9, whose expression in the neural tube at E9.5 is restricted to a segment of the hindbrain known as rhombomere 4. A study of its expression pattern earlier in development revealed that prior to the start of neurulation (E7.5) Hox-2.9 is expressed within a posterior to the embryonic mesoderm that will participate in hindbrain formation. With the onset of neurulation, expression then becomes detectable in the neural plate as well, but only in the part that overlies the Hox-2.9-expressing mesoderm; it is not detected in the more anterior neuroectoderm that will form the future midbrain and forebrain. On the basis of these findings, we propose that the mesoderm is providing cues that serve to instruct the overlying neuroectoderm with respect to its position along the anteroposterior axis and that Hox-2.9 participates in or reflects this process. As neurulation continues and individual segments form, a second phase of expression is detected in the neural tube in which high levels of Hox-2.9 transcripts become restricted to rhombomere 4. Hox-2.9 expression is also detected in the developing branchial arch units of the hindbrain region, in a pattern that suggests to us that here, too, mesoderm is providing a localized signal that induces Hox-2.9 expression, in this case in endoderm of the pharynx and in superficial ectoderm. In general, we interpret the expression patterns of Hox-2.9 in the hindbrain region as suggesting that the specific mechanisms of pattern formation in mammals are fundamentally similar to those of amphibians and avians - i.e. anteroposterior positional information is acquired by mesoderm, mesoderm induces positional values within (neuro-) ectoderm and endoderm, and both events occur within a restricted window of time.
Frohman
M A
MA
Department of Anatomy, School of Medicine, University of California, San Francisco 94143.
Boyle
M
M
Martin
G R
GR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005775:Gastrula / Q000378:metabolism; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D008648:Mesoderm / Q000378:metabolism; D051379:Mice / Q000196:embryology / Q000235:genetics*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D012333:RNA, Messenger