HNF 1 β is required for mesoderm induction in the Xenopus embryo

Mesoderm induction was first demonstrated by Pieter Nieuwkoop in 1969. By recombining animal and vegetal explants, which would in isolation originate ectoderm and endoderm, respectively, mesoderm formed from the animal cap cells (Nieuwkoop, 1969). Successive research has identified candidate mesoderm inducers within the TGFβ and FGF families of molecules (reviewed in Harland and Gerhart, 1997). Several TGFβ factors are involved in mesoderm induction and patterning. Activin, Vg1 (in its activated form, B-Vg1), Nodal-related factors and Derrière can promote development of mesoderm with different dorsoventral values in animal cap induction assays (Green and Smith, 1990; Thomsen and Melton, 1993; Jones et al., 1995; Sun et al., 1999). BMP factors (a subgroup of TGFβ-like molecules) are involved in ventralization of mesoderm, rather than in its initial induction (Dale et al., 1992; Jones et al., 1992; Fainsod et al., 1994). Involvement of TGFβ-like molecules in mesoderm induction and patterning has been proved by impairing their signalling pathways. Overexpression of dominant negative activin receptors completely abolishes mesoderm development, while selective inhibition of Vg1, Xnr1 or Xnr2 signalling also disrupts or suppresses mesoderm formation (HemmatiBrivanlou and Melton, 1992; Chang et al., 1997; Joseph and Melton, 1998; Osada and Wright, 1999; Piccolo et al., 1999). In contrast, impairment of BMP signalling causes dorsalization of ventral mesoderm (Graff et al., 1994). FGF signals are also crucial for mesoderm induction. Overexpression of a dominant negative FGF receptor, either by mRNA injection or in transgenic embryos, demonstrated that FGF signalling is required for mesoderm development and maintenance (Amaya et al., 1991; Kroll and Amaya, 1996). Although able to induce ventral mesoderm in animal caps (Kimelman and Kirschner, 1987; Slack et al., 1987), FGF may work as a competence factor for TGFβ-like-mediated signalling (Cornell et al., 1995). Initial work suggested that mesoderm-inducing signals are produced in the vegetal part of the amphibian embryo very early in development (Jones and Woodland, 1987), well before zygotic gene activation. However, recent observations on heterochronic animal/vegetal conjugates demonstrated that only a low level of mesoderm-inducing signals is produced from vegetal explants before mid-blastula transition (MBT), suggesting that vegetal cells may become fully efficient in releasing inducing signals only after the onset of zygotic transcription (Wylie et al., 1996). The T-box transcription factor VegT/Xombi/Antipodean/Brat (Zhang and King, 1996; Zhang et al., 1998 and references therein) plays a crucial role in this: depletion of its maternal, vegetally localized, mRNA, completely abolishes mesoderm and endoderm formation and impairs the ability of vegetal explants to induce mesoderm from animal cap cells in recombination experiments (Zhang et al., 1998; Kofron et al., 1999). These observations have suggested that mesoderm induction may thus be biphasic, with a first preMBT step of weak induction, and a second post-MBT step of strong induction (Wylie et al., 1996; Zhang et al., 1998; reviewed by Kimelman and Griffin, 1998). Zygotic gene activation within the vegetal cells may therefore set up the biochemical conditions required for their full signalling activity. 1455 Development 127, 1455-1465 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV2500