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University of Macau / Faculty of Science and Technology. / Department of Electromechanical Engineering

During development of the nervous system, signals from specialized organizing centers generate distinct cell types. The signaling molecule, Sonic Hedgehog (SHH) is expressed by the floor plate (FP) and is sufficient to specify the ventral midbrain pattern. In the spinal cord, Bone Morphogenetic Proteins (BMPs) expressed in the roof plate (RP) specify dorsal cell-fates. The attenuation of BMP signaling is required for SHHmediated patterning of the ventral hindbrain and spinal cord, while BMP signaling is required in conjunction with SHH for ventral forebrain patterning. This thesis will focus on the function of SHH and BMPs in the midbrain by examining the molecules ability to pattern and regulate development. Midbrains of Shh[superscript -/-] mice were examined. Some ventral cell fates are specified in the Shh[superscript -/-] mouse in a Ptc1 and Gli1 independent manner. Ventral midbrain induction was observed to be Hh-independent by the existence of a Pax7-negative ventral midbrain territory before embryonic day 9. Interestingly, dorsal markers are not uniformly altered and increased cell death was seen in Shh[superscript -/-] dorsal midbrains. These results suggest specific regulation of dorsal patterning by Shh, rather than a simple deregulation. Several BMPs and their antagonists are expressed in a spatial and temporal manner in the midbrain. Expression of BMPs is seen in the RP, and rostral FP (rFP), which also expresses SHH. BMP signaling was manipulated using in vivo electroporation. NOGGIN misexpression resulted in a loss of RP and a reduction of dorsal cell-fates that was preceded by cell-shape changes, delamination of cells into the lumen and their elimination. This was accompanied by a reduction and alteration of midbrain size and shape. BMP blockade changed N-Cadherin distribution and perturbed pseudostratified morphology of the neurepithelium. Ventrally, BMP blockade resulted in a decrease of proliferation, while increasing differentiation, Notch signaling molecules at the rFP and medial FP markers. However ventral midbrain cell-fates were correctly specified. Notch-Delta signaling was examined in the Mib[superscript -/-] mouse. Different regulation of cell-fates was observed in the midbrain and spinal cord. Mib[superscript -/-] midbrains lacked a mature lateral FP, however ventral cell-fates are specified. Mib[superscript -/-] spinal cords lose Shh expression and several ventral cell-fates. / text

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Cai, Ganhui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 160-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

La crête neurale (CN) est une structure transitoire apparaissant en bordure de la plaque neurale chez les embryons de vertébrés. Au cours du développement embryonnaire, les cellules de la CN prolifèrent, subissent une transition épithélio-mésenchymateuse, migrent et se différencient en de nombreux types cellulaires tels que des neurones et cellules gliales du système nerveux périphérique, des mélanocytes, des cellules musculaires lisses ou des élements du squelette cranio-facial. Afin de mieux comprendre les mécanismes moléculaires contrôlant la prolifération et la spécification des cellules de la CN, nous avons étudié le rôle de deux facteurs de transcription, Hairy2 et Stat3, via des expériences de perte et gain de fonction chez l’embryon de xénope. <p>Le gène Hairy2 code pour un facteur de transcription bHLH-O répresseur. Il est exprimé précocement au niveau de la bordure de la plaque neurale incluant la CN présomptive. Nous avons montré que Hairy2 est requis pour la prolifération des cellules de la CN en aval de signaux FGFs et qu’il maintient les cellules dans un état indifférencié en réprimant l’expression précoce des gènes spécifiques de la CN. Hairy2 réprime aussi la transcription du gène Id3 codant pour un facteur HLH essentiel à la prolifération des cellules de la CN. Id3 affecte également Hairy2. Nous avons observé que la protéine Id3 interagit physiquement avec Hairy2 et bloque son activité, démontrant que les interactions entre Hairy2 et Id3 jouent un rôle important dans la prolifération et la spécification des cellules de la CN. <p>\ / Doctorat en Sciences / info:eu-repo/semantics/nonPublished