Characterization of quiescent state and reactivation of adult muscle precursor cells in Drosophila melanogaster

• Auteur / Autrice : Rajaguru Aradhya
• Direction : Krzysztof Jagla
• Type : Thèse de doctorat
• Discipline(s) : Developmental biology and genetics
• Date : Soutenance le 10/12/2013
• Etablissement(s) : Clermont-Ferrand 1
• Ecole(s) doctorale(s) : École doctorale des sciences de la vie, santé, agronomie, environnement (Clermont-Ferrand)
• Partenaire(s) de recherche : Equipe de recherche : Génétique, reproduction et développement
• Jury : Président / Présidente : Vincent Sapin
• Jury : Examinateurs / Examinatrices : Laurent Perrin
• Jury : Rapporteur / Rapporteuse : Pascal Maire, Michael V. Taylor

Mots clés

Mots clés contrôlés

Biologie du développement

Génétique

Drosophila melanogaster

Mots clés libres

Drosophile

Drosophila

Muscle stem cells

Genetics

Growth

Development

Physiology

Résumé

Pas de résumé disponible

Use of stem cells in regenerative medicine has attracted great interest in the past decade. Muscle stem cells such as satellite cells were shown to regenerate skeletal muscle tissue after injury and to contribute to muscle growth. These properties have raised an enormous interest in using satellite cells for the therapy of skeletal muscle wasting disorders where the intrinsic stem cell population is unable to repair muscle tissue. However, better understanding of the mechanisms controlling satellite cell lineage progression and self-renewal is crucial to exploit the power of these cells in combating myopathic conditions. In the studies described here, the mechanisms regulating the in vivo behavior and maintenance of quiescence of Drosophila Adult Muscle Precursors (AMPs) that share several properties with the vertebrate satellite cells are analyzed. We show that undifferentiated embryonic AMPs display homing behavior and that their survival depends on the somatic muscles. We observe that AMPs establish direct contact with muscle fibers by sending thin filopodia and that this AMP-muscle interaction is crucial for AMPs spatial positioning. Larval muscles also play an important role in promoting the AMP cell proliferation. They achieve this by secreting Drosophila Insulin like peptide 6 (dIlp6) that activate the AMPs from their quiescent state and induce proliferation during the end of the second larval instar. We also demonstrate that Notch acts downstream of Insulin pathway and positively regulates proliferation of AMPs via dMyc. In the second part of the thesis manuscript we report that the affected formation ofadult muscles impacts on persisting abdominal larval templates. In this section role of the Notch signaling pathway in specification of the Adult founder cells is also demonstrated. Finally, we report generation of new tools for the cell type specific genome wide approaches that can be applied to identify global gene expression profiles in quiescent versus activated AMPs. Together these studies identified several new features of AMPs and enhance our understanding on the processes regulating stem cells homing, quiescence and reactivation.