msh may play a conserved role in dorsoventral patterning of the neuroectoderm and mesoderm

Abstract

Many of the mechanisms that govern the patterning of the Drosophila neuroectoderm and mesoderm are still unknown. Here we report the sequence, expression, and regulation of the homeobox gene msh, which is likely to play an important role in the early patterning events of these two tissue primordia. msh expression is first observed in late blastoderm embryos and occurs in longitudinal bands of cells that are fated to become lateral neuroectoderm. This expression is under the control of dorsoventral axis-determination genes and depends on dpp-mediated repression in the dorsal half of the embryo and on fib-(EGF-) mediated repression ventrally. The bands of msh expression define the cells that will form the lateral columns of proneural gene expression and give rise to the lateral row of SI neuroblasts. This suggests that msh may be one of the upstream regulators of the achaete-scute (AS-C) genes and may play a role that is analogous to that of the homeobox gene vnd/NK2 in the medial sector of the neuroectoderm. During neuroblast segregation, msh expression is maintained in a subset of neuroblasts, indicating that msh, like vnd/NK2, could function in both dorsoventral patterning of the neuroectoderm and neuroblast specification. The later phase of msh expression that occurs after the first wave of neuroblast segregation in defined ectodermal and mesodermal clusters of cells points to similar roles of msh in patterning and cell fate specification of the peripheral nervous system, dorsal musculature, and the fat body. A comparison of the expression patterns of the vertebrate homologs of msh, vnd/NK2, and AS-C genes reveals striking similarities in dorsoventral patterning of the Drosophila and vertebrate neuroectoderm and indicates that genetic circuitries in neural patterning are evolutionarily conserved.

Mutations that affect the ability of the vnd/NK-2 homeoprotein to regulate gene expression: Transgenic alterations and tertiary structure

“…msh is expressed initially in the lateral neuroectoderm at stage 6 as two anterior-posterior stripes of cells adjacent and lateral to the cells that express ind. The stripes of cells that express msh change to segmentally repeated clusters of cells that express msh at late stage 8 and, soon afterward, multiple clusters that express msh appear in each hemisegment (26,34). Similar to the expression of ind, repression of msh was not found in the presence of the ectopically expressed UAS-vnd͞NK-2 Y54M mutant transgene (Fig.…”

Dorsoventral patterning in the Drosophila central nervous system: the vnd homeobox gene specifies ventral column identity

“…Lastly, we use the dorsal marker Msh, which labels all dorsal column neuroectoderm and neuroblasts (Fig. 3J;D'Alessio and Frasch 1996;Isshiki et al 1997). Using these markers, we investigate whether vnd is necessary or sufficient to specify ventral column identity within the developing CNS.…”

“…Although vnd is expressed in the ventral column and is required for proper neuroblast formation, the role of vnd in specifying ventral column identity has not been investigated. Dorsal column neuroblast identity is specified, at least in part, by the muscle segment homeobox (msh) gene (Buescher and Chia 1997;Isshiki et al 1997), which is expressed in the dorsal column neuroectoderm and neuroblasts (D'Alessio and Frasch 1996;Isshiki et al 1997).…”

Mapping activation and repression domains of the vnd/NK-2 homeodomain protein

“…The mechanism of initiating the neural pathway of development in the dorsal column of neuroectodermal cells is unknown; however, the muscle segment homeobox gene (msh) is expressed in many neuroectodermal cells and neuroblasts that comprise the dorsal column of neural cells, and the msh homeodomain (HD) protein is known to be required for specification of some of the neuroblasts in the dorsal column (7,8). Expression of a fourth gene that encodes a gene regulatory protein, singleminded, initiates neural development in the ventral midline column of mesoectodermal cells (9,10).…”