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MOLECULAR STUDIES ON HOXD GENES: NEW INSIGHTS INTO THE MECHANISMS OF LIMB DEVELOPMENT AND PATHOGENESIS.

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Fachbereich Biologie, Chemie, Pharmazie, Freie Universität Berlin
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MOLECULAR STUDIES ON HOXD GENES: NEW INSIGHTS INTO THE MECHANISMS OF LIMB DEVELOPMENT AND PATHOGENESIS. Dissertation zur Erlangung des akademischen Grades des Doktors der Naturwissenschaften (Dr. rer. nat.) eingereicht im Fachbereich Biologie, Chemie, Pharmazie der Freien Universität Berlin vorgelegt von BARBARA DŁUGASZEWSKA aus Poznań, Polen September 2005 1. Gutachter: Prof. Dr. Stefan Mundlos 2. Gutachter: Prof. Dr. Horst Kreß Disputation am 5. Dezember 2005 TABLE OF CONTENTS TABLE OF CONTENTS ABBREVIATIONS……………………………………………………………………… 6 1 INTRODUCTION……………………………………………………………….….. 8 1.1 Origin of tetrapod limbs……………………………………………………………..…. 8 1.2 Limb development in embryogenesis…………………………………..………………….... 8 1.2.1 Anatomical view…………………………………………………..……………………. 8 1.2.2 Molecular basis of limb patterning………………………………………………..……... 9 1.2.2.1 Establishment of the proximodistal axis in the limb…………………………………….. 9 1.2.2.2 Establishment of the AP axis………………………………………….……………….. 10 1.2.2.3 Limb patterning along the dorsoventral axis…………………………….………………... 11 1.3 HOX genes in limb development………………………………………….………………... 12 1.3.1 Chromosomal clustering of Hox genes is linked to a specific expression pattern during embryogenesis………………………………………….……………………………... 12 1.3.2 Hox genes and pre-patterning of the embryo…………………….…………………………. 13 1.3.3 Posterior Hoxa and Hoxd genes and their role in limb patterning….………………………….. 13 1.3.4 A special role of the posterior Hoxd genes in the development of digited limbs and the contribution of different pathways to digit formation………….…………………………….. 15 1.3.5 Mechanisms controlling expression of Hox genes...………….……………………………... 16 1.3.5.1 R

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