Title:
Generation of neural primordia in vertebrate embryos by mechanisms that challenge the classical models

Hisato Kondoh
Osaka University Graduate School of Frontier Biosciences

Abstract:
The textbook view holds that segregation of the three germ layers (ectoderm, mesoderm, endoderm) is the process specifying cell lineages in early embryos. Our study challenges this, by showing that paraxial mesoderm (which gives muscle and bone) and posterior neural plate (spinal cord precursor) are in fact derived from common bi-potential precursors “axial stem cells” in the caudal lateral epiblast. This requires Tbx6 (a mesoderm-dedicated regulator) to turn off Sox2 (a neural regulator). Because of this, Tbx6-null mouse embryos develop ectopic neural tubes at the expense of paraxial mesoderm. Cell type specification is therefore separate from germ layer formation. Our study further shows that anterior neural plate (brain precursor) is derived directly from the epiblast (embryonic blastoderm). The mechanisms to derive neural plate differ depending on the embryonic axial levels. These findings will impact on contemporary stem cell research, where the regulation of cell lineage specification is the major issue.
Many textbook descriptions of embryonic development have their basis on the conceptions held in 1920s and 30s, when amphibian embryos were the major subjects and where the Spemann school made major contributions. Researchers then were very alert not to make too definitive conclusions, such as the three germ layer model. Instead, they described many observations unexplainable then, including those indicative of the axial stem cells in amphibian embryos. The current “three germ layer model” in textbooks appears to be produced and dogmatized by their epigones.

References:
Takemoto T, Uchikawa M, Yoshida M, Bell DM, Lovell-Badge R, Papaioannou VE, Kondoh H. Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells. Nature 470, 394-398 (2011).

Iwafuchi-Doi M, Yoshida Y, Onichtchouk D, Leichsenring M, Driever W, Takemoto T, Uchikawa M, Kamachi Y, Kondoh H. The Pou5f1/Pou3f-dependent but SoxB-independent regulation of conserved enhancer N2 initiates Sox2 expression during epiblast to neural plate stages in vertebrates. Developmental Biology 352, 354-366 (2011).

Spemann H. Embryonic development and induction. Yale University Press (1938).

Holtfreter J, Hamburger V. Amphibians in ”Analysis of Development (ed. BH Miller, PA Weiss, V Hamburger)”. pp.230-297, Saunders (1955).

Hamburger V. The heritage of experimental embryology: Hans Spemann and the Organizer. Oxford University Press (1988).