Compensatory functions of the zinc-finger transcription factors Bcl11a and Bcl11b and their effects on neocortical development
InstitutionsInstitut für molekulare und zelluläre Anatomie
Institut für Anatomie und Zellbiologie
This thesis analyses the phenotype of Bcl11a (B-cell lymphoma 11a); Bcl11b (B-cell lymphoma 11b) compound double-mutant mice and the influence of the lost transcription factors on neocortical development. AB-mutants (Bcl11aflox/flox; Bcl11bflox/flox; Emx1Cre/+) show reduced neocortical thickness and manifest with morphologically disturbed deep-layers. Lost co-expression of Bcl11a and Bcl11b in layers V and VI further suggests neocortical deep-layers as a location strongly affected by the knockout. Upon deletion of both Bcl11a and Bcl11b, deep-layer specific marker expression is severely reduced, although it is only influenced minorly in mice lacking either Bcl11a or Bcl11b. AB-mutants are influenced far stronger than loss of either Bcl11a or Bcl11b can explain, which in turn indicates compensatory interactions between Bcl11a and Bcl11b. AB-mutated neurons in neocortical deep-layers lose the ability to express deep-layer transcription factors, but express upper-layer specific markers instead. This study shows that Bcl11a and Bcl11b are of critical importance for specification of neocortical deep-layers. Double-knockout leads to loss of deep-layer specific transcription factors. In utero experiments suggest a fate switch of deep-layer neurons, now expressing upper-layer specific markers. Taken together, the results suggest Bcl11a and Bcl11b as master regulators of neocortical deep-layer specification in neocortical development and further indicate compensatory abilities of the transcription factors.
Subject HeadingsB-Zell-Lymphom [GND]
Genes, bcl-1 [MeSH]
Neocortex; Growth and development [MeSH]