Detailed analysis of Lmx1b expression in multiple organs and its role in dorso-ventral patterning with emphasis on myogenic precursor cells

Lmx1b belongs to a family of LIM homeodomain transcription factors expressed in multiple organs. Targeted disruption of Lmx1b results in ventralization of the limbs, skeletal, brain, kidney and ocular defects which resembles the corresponding human Nail-Patella Syndrome (NPS) (Chen et al. 1998a). The generation of transgenic mice carrying a LacZ reporter gene under the control of the endogenous Lmx1b locus allowed detailed analysis of Lmx1b expression. This study provides novel insights in the expression pattern, determines precisely Lmx1b-positive cell types in tissues, and describes for the first time expression in organs. It was demonstrated that Lmx1b expression is present throughout all stages of mammary gland development and restricted to luminal epithelial cells. Mice targeted for Lmx1b lack mammary glands. These findings indicate that Lmx1b plays a pivotal role in mammary gland development. Indeed, female patients with NPS display poor breast development (Sweeney et al. 2003). It is shown that Lmx1b expression is restricted to podocytes in the kidney, indicating the involvement of Lmx1b in nephropathy of NPS patients. No expression was detected in heart, liver and spleen. Lmx1b is involved in pattern formation of the limb and exhibits expression throughout all stages of embryonic development restricted to the dorsal limb mesenchyme. Hereby, Lmx1b expression marks a sharp boundary towards the ventral part of the limb. It is shown that dorsal Lmx1b-positive cells do not sort out from ventral Lmx1b-negative cells. This suggests that the maintenance of the boundary is not triggered by differential cell adhesion in the whole limb, maybe only at the boundary itself. <br>Moreover, interspecific grafting experiments using quail-chick chimeras showed that migrating cells have restricted movement within the dorsal or ventral compartment they attain during transplantation. These findings indicate that migrating cells respect the boundary between the dorsal and ventral compartment and no exchange occurs. Interestingly, although Lmx1b is known as a marker for the dorsal limb mesenchyme, myogenic precursor cells invading the dorsal part of the limb are shown to be devoid of expression. It is also assumed that differentiated muscle lacks Lmx1b expression. In all, this study extends the understanding of limb pattern formation and reveals novel findings concerning proximo-distal differences and migratory pathways. The discovery of Lmx1b expression in organs and its detailed description forms an important basis for further investigations to finally understand and treat human NPS.

Author dc:creator

• Schweizer, Heiko

Contributors dc:contributor

• Brand-Saberi, Beate

• Extremitäten
• Brustdrüsen
• Reportergen
• Lbx1
• Muskelvorläuferzellen
• Muskelentwicklung
• Lmx1b
• cell migration
• Nail-Patella-Syndrome
• mammary gland development

Repository record source_url

https://freidok.uni-freiburg.de/data/1762

OAI identifier oai:identifier

oai:freidok.uni-freiburg.de:1762