The Interactive Fly
Evolutionarily conserved developmental pathways
The understanding of pathways that induce mammalian cardiac and somaticmuscle is incomplete, but in each case, elements common to both Drosophilaand mammals suggest an evolutionarily conserved pathway. Induction of cardiacmuscle in Drosophila requires tinmanacting downstream of twistand decapentaplegic. Themammalian homolog of Tinman, Nkx2-5, is expressed in precardiac mesodermand in the myocardium of embryonic and fetal hearts. A Xenopus homologis likewise expressed in the heart region. A mammalian homolog of Bagpipe, involved in specification of visceral musculature in Drosophila, has been discovered in Xenopus. Xbap, like bagpipe is expressed in the developing musculature of the midgut. However, a second, novel role in development is suggested by the observation that Xbap is expressed in the region of the developing facial cartilage, a neural crest derivative.
The axial structures, consisting of the notochord and the neural tube, play an essential role in the dorsoventral patterning of somites and in the differentiation of their many cell lineages in vertebrates. Because Drosophila lacks a dorsal nervous cord and notochord, it is often thought that the roles of these tissues are not conserved. Nevertheless, expression of Nkx-3.1 (homologous to Drosophila bagpipe), functions downstream of Sonic hedgehog in vertebrates as it does in flies. The role of the axial structures was studied by using Nkx-3.1 as a medial somitic marker in explant in vitro assays. Nkx-3.1 is dynamically expressed during somitogenesis only in the youngest, most newly-formed somites at the caudal end of the embryo. The expression of Nkx-3.1 in pre-somitic tissue explants is induced by the notochord and maintained in newly-differentiated somites by the notochord and both ventral and dorsal parts of the neural tube. Sonic hedgehog is one of the signaling molecules that can reproduce the effect of the axial structures. Shh can induce and maintain Nkx-3.1 expression in pre-somitic mesoderm and young somites, but not in more mature, differentiated ones (Kos, 1998). In Drosophila, bagpipe expression is likewise regulated by Hedgehog signals, but in the case of Drosophila, HH signals emanate from the overlying ectoderm (Azpiazu, 1996).
A second example exists for a conserved role for external signals in mesoderm induction. Drosophila induction of the homeobox gene tinman, and subsequent heart formation, are both dependenton dpp signaling from overlying ectoderm. In order to define vertebrate heart-inducing signals dpp-homologs have been sought that are expressed in stage 4 chicken embryos. The majority of transcriptsare found to be BMP-2 among several other members of the BMP family. From embryonic stage 4 onwards cardiogenic mesoderm appears to be in close contact to BMP-2 expressing cellsthat initially are present in lateral mesoderm and subsequently after headfold formation in thepharyngeal endoderm. In order to assess the role of BMP-2 for heart formation, gastrulating chickembryos in culture were implanted with BMP-2 producing cells. BMP-2 implantation results inectopic cardiac mesoderm specification. BMP-2 is able to induce Nkx2-5 expression (Drosophila homolog: Tinman) ectopicallywithin the anterior head domain, while GATA-4 (Drosophila homolog: Serpent) is induced more caudally. However, cardiogenic inductionby BMP-2 remains incomplete, since neither Nkx2-8 nor the cardiac-restricted structuralgene VMHC-1 become ectopically induced. These results suggest that BMP-2 is part of thecomplex of cardiogenic signals and is involved in the patterning of early mesoderm similar to the role ofdpp in Drosophila (Andrée, 1998).
Induction of somatic musculaturerequires two components: (1) a basic helix-loop-helix transcription factors(bHLH) and (2) a MADS box transcription factor:
(1) The bHLH transcription factors involved are: Nautilusin Drosophila, and MyoD homologs in vertebrates. Both Nautilus and MyoDhomologs require a cofactor: Daughterlessin Drosophila, and E12 in vertebrates. Nautilus acts downstream of twistand decapentaplegic.
(2) Myocyte enhancer factor 2 is the MADS box transcription factor. ForDrosophila MEF2, there are two Xenopus homologsand several mammalian homologs. Many muscle protein promoters have bindingsites for both bHLH heterodimers and MEF2, suggesting that the two componentsintegrate their action directly on target promoters.
Andrée, B., et al. (1998). BMP-2 induces ectopic expression of cardiaclineage markers and interferes with somiteformation in chicken embryos. Mech. Dev. 70(1-2): 119-131. PubMed Citation: 9510029
Azpiazu, N., et al. (1996). Segmentation and specification of the Drosophila mesoderm. Genes Dev. 10: 3183-94. PubMed Citation: 8985186
Kos, L., Chiang, C. and Mahon, K. A. (1998). Mediolateral patterning of somites: multiple axial signals, including Sonic hedgehog, regulate Nkx-3.1 expression. Mech. Dev. 70(1-2): 25-34. PubMed Citation: 9510022
date revised: 10 March 98
Developmental Pathways conserved in Evolution
Home page: The InteractiveFly © 1995, 1996 Thomas B. Brody, Ph.D.
The Interactive Fly resides on the
Society for Developmental Biology's Web server.