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The pivotal mechanisms that govern the correct patterning and regionalization of the distinct areas of the mammalian CNS are driven by key molecules that emanate from the so-called secondary organizers at neural plate and tube stages. FGF8 is the candidate morphogenetic molecule to pattern the mesencephalon and rhombencephalon in the isthmic organizer (IsO). Recognizable relevance has been given to the intracellular pathways by which Fgf8 is regulated and modulated. In chick limb bud development, a dual mitogen-activated protein kinase phosphatase-3 (Mkp3) plays a role as a negative feedback modulator of Fgf8 signaling. We have investigated the role of Mkp3 and its functional relationship with the Fgf8 signaling pathway in the mouse IsO using gene transfer microelectroporation assays and protein-soaked bead experiments. Here, we demonstrate that MKP3 has a negative feedback action on the MAPK/ERK-mediated FGF8 pathway in the mouse neuroepithelium. Keywords: Mouse; Neural tube; Embryogenesis; Gene expression regulation; Isthmic organizer; Fgf8; Mkp3: Fibroblast growth factors; Secondary organizers; P13K cascade; MAP kinase cascade; Electroporation: Microspheres

The function of cerl-2 a novel Nodal antagonist, which displays a unique asymmetric expression on the right side of mouse node, is studied. Cerl-2 plays a key role in restricting the Nodal signaling pathway toward the left side of the mouse embryo by preventing its activity in the right side.

We analyzed the endogenous requirement for Cerberus in Xenopus head development. 'Knockdown' of Cerberus function by antisense morpholino oligonucleotides did not impair head formation in the embryo. In contrast, targeted increase of BMP, Nodal and Wnt signaling in the anterior dorsal-endoderm (ADE) resulted in synergistic loss of anterior head structures, without affecting more posterior axial ones. Remarkably, those head phenotypes were aggravated by simultaneous depletion of Cerberus. These experiments demonstrated for the first time that endogenous Cerberus protein can inhibit BMP, Nodal and Wnt factors in vivo. Conjugates of dorsal ectoderm (DE) and ADE explants in which Cerberus function was 'knocked down' revealed the requirement of Cerberus in the ADE for the proper induction of anterior neural markers and repression of more posterior ones. This data supports the view that Cerberus function is required in the leading edge of the ADE for correct induction and patterning of the neuroectoderm. [ABSTRACT FROM AUTHOR]