BMP-4-responsive regulation of dorsal–ventral patterning by the homeobox protein Mix.1

Abstract

In an expression screen for factors that pattern or induce ventral mesoderm, we isolated a complementary DNA encoding Mix.1, a paired class homeobox gene with no previously known function. Injection of Mix.1 messenger RNA results in extensive blood formation in the whole embryo and transforms dorsal mesoderm to a ventral fate. Mix.1 expression is induced by bone morphogenetic protein-4 (BMP-4), and a dominant inhibitory mutant of Mix.1 can restore a dorsal axis in embryos ventralized by ectopic BMP-4 expression. Mix.1 can form heterodimers with the dorsalizing gene siamois, which encodes a homeodomain protein that is structurally similar to Mix.1. Furthermore, Mix.1 blocks the duplicated axis induced by ectopic siamois expression. Our findings indicate that Mix.1 participates in a BMP-4 signalling pathway to pattern ventral mesoderm, and suggest a model whereby dimerization of homeodomain proteins regulates dorsal-ventral patterning.

Control of gastrula cell motility by the Goosecoid/Mix.1/ Siamois network: Basic patterns and paradoxical effects

“…Siamois (Sia) (Lemaire et al, 1995) and the closely related Twin (Laurent et al, 1997) represent yet another group of pairedclass factors, which are involved in dorsoventral axis specification. Like Gsc, Sia can form heterodimers with Mix.1 (Mead et al, 1996), and both Sia (Carnac et al, 1996) and Mix.1 (Latinkic and Smith, 1999) can activate Gsc transcription.…”

Characterization of Homo- and Heterodimerization of Cardiac Csx/Nkx2.5 Homeoprotein

“…However, a very limited number of studies have addressed the homo-and heterodimerization of HD-containing transcription factors among more than 400 members of HD proteins from yeast to human. Homodimerization ability has been demonstrated for Oct1 (10), Paired (11), Cdx2 (12), Even-skipped (13), Mix.1 (14), and Pit1 (15). Heterodimerization was shown for HNF1␣-HNF1␤ (16), Oct1-Oct2 (15), Mix.1-Siamois (14), MCM1-MAT␣2 (17,18), and Extradenticle-Ultrabithorax (19).…”

PBX proteins: much more than Hox cofactors

“…Although this aspect of Pbx homodimerization has not been further explored, it could play a role in gene regulation through a competition between various partners. Indeed, several studies have addressed the importance of homodimerization for other homeodomain-containing transcription factors such as Oct1 (Poellinger and Roeder, 1989), Paired (Wilson et al, 1993), Cdx2 (Suh et al, 1994), Evenskipped (Hirsch and Aggarwal, 1995), Mix1 (Mead et al, 1996) and Pit1 (Jacobson et al, 1997). Homodimerization of Pbx proteins might be a way of preventing their interaction with other transcription factors and their binding onto certain gene promoters.…”