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      Practical Lessons from Theoretical Models about the Somitogenesis

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          Abstract

          Vertebrae and other mammalian repetitive structures are formed from embryonic organs called somites. Somites arise sequentially from the unsegmented presomitic mesoderm (PSM). In mice, a new bilateral pair of somites arise every two hours from the rostral PSM. On the other hand, cells are added to the caudal side of the PSM due to cell proliferation of the tail bud. Somite formation correlates with cycles of cell-autonomous expression in the PSM of genes like Hes7. Because the somitogenesis is a highly dynamic and coordinated process, this event has been subjected to extensive theoretical modeling. Here, we describe the current understanding about the somitogenesis in mouse embryos with an emphasis on insights gained from computer simulations. It is worth noting that the combination of experiments and computer simulations has uncovered dynamical properties of the somitogenesis clock such as the transcription/translation delays, the half-life and the synchronization mechanism across the PSM. Theoretical models have also been useful to provide predictions and rigorous hypothesis about poorly understood processes such as the mechanisms by which the temporal PSM oscillations are arrested and converted into an spatial pattern. We aim at reviewing this theoretical literature in such a way that experimentalists might appreciate the resulting conclusions.

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          WNT and DKK determine hair follicle spacing through a reaction-diffusion mechanism.

          Mathematical reaction-diffusion models have been suggested to describe formation of animal pigmentation patterns and distribution of epidermal appendages. However, the crucial signals and in vivo mechanisms are still elusive. Here we identify WNT and its inhibitor DKK as primary determinants of murine hair follicle spacing, using a combined experimental and computational modeling approach. Transgenic DKK overexpression reduces overall appendage density. Moderate suppression of endogenous WNT signaling forces follicles to form clusters during an otherwise normal morphogenetic program. These results confirm predictions of a WNT/DKK-specific mathematical model and provide in vivo corroboration of the reaction-diffusion mechanism for epidermal appendage formation.
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            Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis.

            We have identified and characterized c-hairy1, an avian homolog of the Drosophila segmentation gene, hairy. c-hairy1 is strongly expressed in the presomitic mesoderm, where its mRNA exhibits cyclic waves of expression whose temporal periodicity corresponds to the formation time of one somite (90 min). The apparent movement of these waves is due to coordinated pulses of c-hairy1 expression, not to cell displacement along the anteroposterior axis, nor to propagation of an activating signal. Rather, the rhythmic c-hairy mRNA expression is an autonomous property of the paraxial mesoderm. These results provide molecular evidence for a developmental clock linked to segmentation and somitogenesis of the paraxial mesoderm, and support the possibility that segmentation mechanisms used by invertebrates and vertebrates have been conserved.
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              A clock and wavefront model for control of the number of repeated structures during animal morphogenesis.

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                Author and article information

                Journal
                Gene Regul Syst Bio
                Gene Regulation and Systems Biology
                Gene Regulation and Systems Biology
                Libertas Academica
                1177-6250
                2007
                28 May 2007
                : 1
                : 35-42
                Affiliations
                Institute for Virus Research, Kyoto University, and Japan Science and Technology Agency, CREST Kyoto, Japan
                Author notes
                Correspondence: Ryoichiro Kageyama, Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan. Tel: 81-75-751-4011; Email: rkageyam@ 123456virus.kyoto-u.ac.jp .
                Article
                grsb-2007-035
                2759138
                19936076
                60661e51-79fe-4d9a-8524-d4e032b19b2a
                © 2007 The authors.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Categories
                Review

                Genetics
                hes7 oscillation,theoretical models,notch signaling,fgf signaling,mouse somitogenesis,wnt signaling

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