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

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.

Transcriptional profiling of sequentially generated septal neuron fates

“…The renaming we suggest is based on the similarities between the rostral and caudal portions of the developing septum and the LGE and the MGE progenitor zones, respectively. While the rostral septum and the LGE serve as the anatomical templates for their mature derivatives (the septum proper and the striatum), the MGE and the septal eminence are largely transient structures with merely vestigial counterparts in the mature brain ( Delgado and Lim, 2017 ; Delgado et al, 2020 ; Merkle et al, 2014 ). The main role of the MGE and the septal eminence during embryonic development is to generate cells destined to occupy other areas of the brain (cortical interneurons in the MGE, multiple septal neurons and basal forebrain cholinergic neurons in the septal eminence).…”

Transcriptional profiling of sequentially generated septal neuron fates

“…LGE-like and the MGE-like progenitor zones, respectively. While the rostral septum and the LGE serve as the anatomical templates for their mature derivatives (the septum proper and the striatum), the MGE and the septal eminence are largely transient structures with merely vestigial counterparts in the mature brain (Delgado and Lim, 2017;Delgado et al, 2020;Merkle et al, 2014). The main role of the MGE and the septal eminence during embryonic development is to generate cells destined to occupy other areas of the brain (cortical interneurons in the MGE, multiple septal neurons and basal forebrain cholinergic neurons in the septal eminence).…”

Maintenance of neural stem cell positional identity by mixed-lineage leukemia 1

“…Mixed-lineage leukemia 1 (Mll1) is the mammalian homolog of the Drosophila gene trithorax, and these genes are required to maintain-but not induce-the proper regional expression of Hox cluster genes that determine the anterior-posterior body plan during early embryogenesis (14)(15)(16). The vertebrate telencephalon develops from the most anterior aspect of the neural tube, and telencephalic NSCs remain regionally distinct throughout development and into postnatal life (9,17,18). To investigate whether Mll1 is required to maintain Nkx2-1 in ventral NSCs through embryonic and postnatal development, we used the Nkx2-1-Cre driver to delete conditional alleles of Mll1 (Mll1 F ) (19).…”