Regulation of the NK-2 Homeobox Gene in the Developing Nervous System
This abstract for a paper to be delivered at Cold Spring Harbor explains the conditions under which the NK-2 homeobox gene
is expressed differently in different organisms. Results suggest that the NK-2 gene receives and integrates information and
then generates cells that are precursors of neuroblasts.
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Webber, Keith O.
Nirenberg, Marshall W.
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Regulation of the NK-2 Homeobox Gene in the Developing Nervous System. Mellerick, D., Nakayama, K., Nakayama, N., Kim, Y.,
Webber, K., Lad, R., and Nirenberg, M.; Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, NIH,
Nuclei in the ventral half of the Drosophila ventrolateral neurogenic anlage and in the procephalic region initially express
NK-2 in late stage 4/early stage 5 embryos. These nuclei give rise to subsets of NK-2 positive neuroectodermal cells, neuroblasts,
ganglion mother cells (GMC), and neurons in the subesophageal ganglion, ventral nerve cord, stomatagastric nervous system
and some cephalic ganglia. NK-2 mRNA also is expressed in the anterior and posterior midgut primordia. Later in development,
NK-2 is detected in the PNS. Initially, NK-2 is expressed in a fairly uniform horizontal stripe, about 7 nuclei in width,
on each side of the embryo that extends from 0 to 90% EL. During gastrulation, the horizontal stripe of NK-2 positive cells
is subdivided into 12 vertical stripes due to decreases in NK-2 mRNA in some cells. As development proceeds NK-2 expression
decreases in additional cells resulting in the formation of 2 clusters of NK-2 positive neuroectodermal cells per hemisegment
adjacent to the mesectoderm in stage 9 or 10 embryos. Predominantly medial neruoblasts segregate from these clusters and
continue to express NK-2 in GMC and neuronal progeny.
Genes that affect NK-2 expression were identified by in situ hybridization in various mutant backgrounds. In snail mutants,
the developmental fate of mesodermal prescursor cells was changed to cells that expressed the NK-2 gene, while in twist/snail
double mutants, cells that develop as mesoderm or mesectoderm in wild type embryos expressed NK-2, as well as ventral neuroectodermal
cells. In single-minded mutants, which lack mesectodermal cells, NK-2 expressing neuroectodermal cells, neuroblasts, and
their progeny were detected at the ventral midline. A similar pattern of NK-2 expression was detected in E(splD)m8 mutants.
These results suggest that NK-2 is activated in the ventral 45% of the embryo, presumably by dorsal, but is not expressed
in mesoderm due to repression by snail, or in mesectoderm due to repression by single-minded and m8 protein.
snail is expressed in neuroblasts, which should repress activation of the NK-2 gene by dorsal. The 5'-flanking region
of the NK-2 gene contains many binding sites for NK-2 protein, which suggests that NK-2 protein may by required to maintain
NK-2 gene expression (Wang et al, these abstracts). Putative sites for dorsal, snail, and m8 overlap, or are adjacent to,
many NK-2 protein binding sites. These results suggest that the NK-2 gene receives and integrates information from the ventral-dorsal
and anterior-posterior gradients of gene regulators to generate an alternating pattern of clusters of neuroectodermal cells
that are precursors of different types of neuroblasts.