Maintenance of Positional Identity of Neural Progenitors in the Embryonic and Postnatal Telencephalon.

Ryan N Delgado,Daniel A Lim

doi:10.3389/fnmol.2017.00373

Abstract

Throughout embryonic development and into postnatal life, regionally distinct populations of neural progenitor cells (NPCs) collectively generate the many different types of neurons that underlie the complex structure and function of the adult mammalian brain. At very early stages of telencephalic development, NPCs become organized into regional domains that each produce different subsets of neurons. This positional identity of NPCs relates to the regional expression of specific, fate-determining homeodomain transcription factors. As development progresses, the brain undergoes vast changes in both size and shape, yet important aspects of NPC positional identity persist even into the postnatal brain. How can NPC positional identity, which is established so early in brain development, endure the many dynamic, large-scale and complex changes that occur over a relatively long period of time? In this Perspective article, we review data and concepts derived from studies in Drosophila regarding the function of homeobox (Hox) genes, Polycomb group (PcG) and trithorax group (trxG) chromatin regulators. We then discuss how this knowledge may contribute to our understanding of the maintenance of positional identity of NPCs in the mammalian telencephalon. Similar to the axial body plan of Drosophila larvae, there is a segmental nature to NPC positional identity, with loss of specific homeodomain transcription factors causing homeotic-like shifts in brain development. Finally, we speculate about the role of mammalian PcG and trxG factors in the long-term maintenance of NPC positional identity and certain neurodevelopmental disorders.

Highlights

Throughout embryonic development and into postnatal life, regionally distinct populations of neural progenitor cells (NPCs) collectively generate the many different types of neurons that underlie the complex structure and function of the adult mammalian brain
How can NPC positional identity, which is established so early in brain development, endure the many dynamic, large-scale and complex changes that occur over a relatively long period of time? In this Perspective article, we review data and concepts derived from studies in Drosophila regarding the function of homeobox (Hox) genes, Polycomb group (PcG) and trithorax group chromatin regulators
Based on data and concepts described in sections above, we suggest that certain chromatin regulators are integral to the maintenance of NPC positional identity

Summary

POSITIONAL IDENTITY AS A DETERMINANT OF CELL FATE

Cell fate determination is a fundamental aspect of metazoan development. At very early stages of mammalian embryogenesis, differences in cell position begin to correspond to distinct developmental fates. In the absence of Ubx, the third thoracic segment fails to generate halters and instead makes an additional wing, an appendage that normally develops from an adjacent segment This change in segment identity is known as a ‘‘homeotic shift’’ and results from the ectopic expression of Antp, a Hox gene responsible for wing development. Similar to phenotypes observed in Drosophila, Hox gene expression is established normally in Mll1null mice but is not properly maintained, resulting in homeotic transformations of their axial skeleton (Yu et al, 1995, 1998). PcG and trxG genes are key components of a ‘‘cellular memory system’’ that maintains the positional identity of progenitor cells in mammalian development

POSITIONAL IDENTITY IN THE EMBRYONIC TELENCEPHALON

POTENTIAL MECHANISMS UNDERLYING THE MAINTENANCE OF NPC POSITIONAL IDENTITY

THE IMPORTANCE OF UNDERSTANDING HOW NPCs MAINTAIN POSITIONAL IDENTITY

Findings

CONCLUDING REMARKS