Long Research Description
Cell fate specification throughout development is governed by a network of complex transcription factor (TF) interactions. A prime example of this regulation can be found in the developing ventral spinal cord: across vertebrates, a Sonic Hedgehog (Shh) signaling gradient initiates a network of cross-repressive TF interactions, ultimately specifying five principal progenitor domains. Two of the TFs involved in this cross-regulatory network are NKX2-2 and OLIG2—which define adjacent, non-overlapping p3 (NKX2-2-expressing, interneuron progenitor) and pMN (OLIG2-expressing, motor neuron progenitor) domains.
However, while NKX2-2 represses OLIG2 during motor neuron (MN) generation, their co-expression in the same domain becomes essential for the differentiation of oligodendrocytes (OLs) immediately after motor neurogenesis is complete. Additionally, the Wichterle lab has recently found that a human-specific progenitor domain, characterized by unexpected, early NKX2-2/OLIG2 co-expression, also gives rise to motor neurons—and exhibits expanded and protracted motor neurogenesis.
The overarching goal of my thesis work is to address this dynamic and context-dependent cross-regulation of NKX2-2 and OLIG2 in the developing spinal cord. I hope to unravel the molecular mechanisms underlying the differences in repressive activity between these TFs in human and mouse developmental contexts and to determine the functional consequences of their expression/co-expression on cell fate specification and motor neurogenesis.
