Disease relevance of Dr

• Specifically, we demonstrate that mutation of the muscle identity gene msh and misexpression of the heart identity gene lb lead to heart hyperplasia with similar cell fate modifications [1].

High impact information on Dr

• The establishment of dorsoventral column identity involves negative regulation: Vnd represses ind in the ventral column, whereas ind represses msh in the intermediate column [2].
• In Drosophila the central nervous system develops from three longitudinal columns of cells: ventral cells that express the vnd/nk2 homeobox gene, intermediate cells, and dorsal cells that express the msh homeobox gene [2].
• The homeo box of this new gene shows remarkable similarity to the Drosophila Msh homeo box that we designate as the prototype for this family [3].
• Loss- and gain-of-function analyses show that msh maintains Iro-C repressed in the hinge, while Iro-C prevents high level expression of msh in the notum [4].
• Here, we report that the homeobox gene msh (muscle segment homeobox) acts downstream of apterous to confer dorsal identity in wing development [5].

Biological context of Dr

• 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 [6].
• 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 [6].
• We then determined the function of the muscle segment homeobox (msh) gene in myogenesis. msh encodes a homeobox-containing protein, vertebrate homologues of which are known as Msxs [7].
• The amino acid sequence of the msh homeobox domain is highly homologous to the homeodomains of the Drosophila S59 and empty spiracles genes and the Hox 7 and Hox 8 family of vertebrate homeobox genes [8].
• By late stage 14 of embryonic development, msh expression is greatly reduced or absent in most or all mesoderm and muscle but continues in CNS until hatching [8].

Anatomical context of Dr

• We also show that, in the anterior brain (protocerebrum), normal production of early glial cells is independent from msh and vnd, in contrast to the posterior brain (deuto- and tritocerebrum) and to the ventral nerve cord [9].
• msh may play a conserved role in dorsoventral patterning of the neuroectoderm and mesoderm [6].
• 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 [6].
• We show that msh is expressed in the dorsal and lateral domains of muscle progenitors and is required for the specification of the progenitor cells [7].
• The expression of msh is initially detected at about stage 6 in the dorsal lateral ectoderm of the embryo and later in the developing central (CNS) and peripheral nervous systems [8].

Associations of Dr with chemical compounds

• In addition, the 5' end of msh has 52% sequence identity to the 5' end of the empty spiracles gene and encodes several stretches of amino acids rich in serine, alanine, proline, glutamine, and acidic amino acids, indicating potential domains of regulatory activity [8].

Other interactions of Dr

• Whereas in the trunk Vnd negatively regulates ind, Vnd does not repress ind (but does repress msh) in the ventral pNE and NBs [9].
• Finally, we show that the msh domain is defined by repression: it occurs only where Dpp, Vnd, and Ind activity is low [10].
• These mesodermal cells, which continue to express msh in daughterless mutant embryos, undergo an increase in cell number in neurogenic mutants [8].

References