Anterior neural plate regionalization in cripto null mutant mouse embryos in the absence of node and primitive streak

Abstract

The relation between the role of the organizer at the gastrula stage and the activity of earlier signals in the specification, maintenance, and regionalization of the developing brain anlage is still controversial. Mouse embryos homozygous for null mutation in the cripto gene die at about 9.0 days postcoitum (d.p.c.) and fail to gastrulate and to form the node (the primary organizer). Here, we study the presence and the distribution of anterior neural plate molecular domains in cripto null mutants. We demonstrate that, in cripto(-/-) embryos, the main prosencephalic and mesencephalic regions are present and that they assume the correct topological organization. The identity of the anterior neural domains is maintained in mutant embryos at 8.5 d.p.c., as well as in mutant explants dissected at 8.5 d.p.c. and cultured in vitro for 24 h. Our data imply the existence of a stable neural regionalization of anterior character inside the cripto(-/-) embryos, despite the failure in both the gastrulation process and node formation. These results suggest that, in mouse embryos, the specification of the anterior neural identities can be maintained without an absolute requirement for the embryonic mesoderm and the node.

Molecular mechanisms controlling brain development: an overview of neuroepithelial secondary organizers

“…When Cerberus is ectopically expressed in Xenopus embryos, it induces nearly complete head structures (Bouwmeester et al, 1996). Other proteins such as Noggin, Follistatin, Cripto and Chordin also induce anterior neural tissues, but these genes may not be essential for AP patterning (Liguori et al, 2003 andLamb et al, 1993;Hemmati-Brivanlou et al, 1994;Lamb and Harland, 1995; for review see Doniach, 1993).…”

“…When Cerberus is ectopically expressed in Xenopus embryos, it induces nearly complete head structures (Bouwmeester et al, 1996). Other proteins such as Noggin, Follistatin, Cripto and Chordin also induce anterior neural tissues, but these genes may not be essential for AP patterning (Liguori et al, 2003 andLamb et al, 1993;Hemmati-Brivanlou et al, 1994;Lamb and Harland, 1995; for review see Doniach, 1993).Two homeodomain transcription factors, Lim1 and Otx2, are expressed in the tissues underlying the anterior neural plate and seem to be essential for the development of anterior CNS structures. Loss-of-function mutants result in mouse embryos lacking forebrain and midbrain, suggesting that Lim1 and Otx2 have a role in early AP patterning (Acampora et al, 1995;Matsuo et al, 1995;Shawlot and Behringer, 1995; Ang et al, 1996).…”

Nodal-dependant Cripto signaling in ES cells: from stem cells to tumor biology

“…This expression pattern suggests that cripto may play a role in the early events leading to heart morphogenesis. Mouse embryos deficient for the cripto gene die around day 7.5 of embryogenesis due to defects in mesoderm formation and axial organization (Ding et al, 1998;Liguori et al, 2003). Notably, mouse cripto mutants exhibit defects in myocardial development as evidenced by the absence of expression of terminal myocardial differentiation genes such as aMHC and MLC2v (Ding et al, 1998;Xu et al, 1998).…”

“…Knockout mice for the cripto gene consist mostly of anterior neuroectoderm and lack posterior structures (Ding et al, 1998;Liguori et al, 2003); however, the critical timing of Cripto signaling required to achieve neural specification in mammalian embryos is not known. Intriguingly, disruption of cripto leads to spontaneous neuronal differentiation of ES cells in the presence of serum and in the absence of either specific inducers or defined culture conditions (Parisi et al, 2003).…”

Characterization of the functional properties of the neuroectoderm in mouse Cripto-/-embryos showing severe gastrulation defects

“…However, evidence is accumulating against this two-step model. If the mouse primary organizer is ablated either surgically during gastrulation or genetically by deletion of HNF3β or Cripto, a neural plate still forms (Ang and Rossant, 1994;Davidson et al, 1999;Ding et al, 1998;Klingensmith et al, 1999;Liguori et al, 2003;Weinstein et al, 1994). The mouse Cripto null mutant embryos are very informative.…”