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| Louis Puelles |
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Dept.Morphological Sciences, Fac.Medicine, Univ.Murcia, E-30100, Murcia, Spain
e-mail: puelles@um.es |
Presentation: |
| 2002-10-05, 10:55-11:35 |
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| A molecular "Bauplan" of the central nervous system. |
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| The concept of a Bauplan or construction plan of a complex form as is the brain implies a synthetic account of the essential structural parts and their mutual neighborhood relationships. Essential means here evolutionarily conserved. The constructional aspect implicit in the concept of Bauplan makes it appropriate to fundament Bauplan analysis in the early embryo, since that is when it is established. Further development adds mainly growth and collateral morphogenetic deformation, to give the final mature phenotype. The latter process introduces considerable vatiation across species sharing the same Bauplan. This is a morphological concept, so that use of molecular genetic markers here does not refer to any occult linear "Bauplan" in the genome, but to the advantages of using such markers for better and earlier morphological characterization of the different parts of the brain during development. Combinations of gene functions acting cell-autonomously and epigenetically generate the developmental processes that construct the brain and regionalize it into distinct parts. Evolution of genomes tends to stabilize given early morphogenetic patterns, which resultingly are shared by large radiations of species. Morphogenesis of the central nervous system of vertebrates is strongly conservative, due to its fundamental role in survival, leading to the existence of a neural Bauplan. A number of developmental genes show already at neural plate stages a correlation of the boundaries of their expression domains with experimentally determined boundaries of prospective fate, and new such boundaries are subsequently added at early neural tube stages. Analysis of such patterns in connection with fate, morphology, growth patterns and differentiation patterns allows us to obtain deeper insight into the Bauplan of the central nervous system. This molecular- and experimental-based approach provides a causal dimension that purely morphological constructions lacked before. The Bauplan model we have been developing under the name of "prosomeric model" seems to apply to all vertebrates. It postulates three sorts of essential (conserved) structural elements: 1) a length axis, defined as the floorplate domain of the neural tube caused by axial mesodermal induction processes (note we evade here ideal axial lines through the neural tube cavity or anywhere else); 2) longitudinal zones caused by dorsoventral patterning by interaction of ventralizing and dorsalizing effects (floorplate, basal and alar plates and roofplate); 3) transversal zones or neuromeres, a result of anteroposterior patterning by early extreme organizers (node and anterior visceral endoderm), complemented by later secondary organizers (i.e., isthmic organizer, or retinoic acid gradient in the hindbrain). The model further postulates more advanced secondary and even tertiary regionalization of the primary checker-board pattern of divisions, until fate-homogeneous histogenetic areas are segregated (each subdivision with a characteristic constellation of genetic specification conditions). The mutual topological relationships collating all these elements together are symmetry relationships across the midline floorplate and orthogonality of longitudinal zones relative to transversal neuromeres. Parametric external relationships with neural crest derived peripheral elements, somites, branchial arches, placodes, etcetera also obtain. So far, this model is consistent with most gene expression patterns and available causal analysis, and has proven a very potent instrument as a mental framework for analysis of comparative brain structure, gene expression, and mutant phenotypes. A number of examples of gene expression patterns supporting our morphological interpretation will be shown, extending from neural plate stages into tertiary regionalizations within the telencephalic pallium and subpallium.[work done in collaboration with J.L.R.Rubenstein, San Francisco] |
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