Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

Regulation of chromatin accessibility and gene expression in the developing hippocampal primordium by LIM-HD transcription factor LHX2.

Publication Type

Journal Article

Date of Publication

August 1, 2023

Journal

PLoS genetics

Volume/Issue

19/8

ISSN

1553-7404

In the mammalian cerebral cortex, the hippocampal primordium (Hcp) occupies a discrete position in the dorsal telencephalic neuroepithelium adjacent to the neocortical primordium (Ncp). We examined transcriptomic and chromatin-level features that distinguish the Hcp from the Ncp in the mouse during the early neurogenic period, embryonic day (E)12.5. ATAC-seq revealed that the Hcp was more accessible than the Ncp at this stage. Motif analysis of the differentially accessible loci in these tissues revealed LHX2 as a candidate transcription factor for modulating gene regulatory networks (GRNs). We analyzed LHX2 occupancy profiles and compared these with transcriptomic data from control and Lhx2 mutant Hcp and Ncp at E12.5. Our results revealed that LHX2 directly regulates distinct genes in the Hcp and Ncp within a set of common pathways that control fundamental aspects of development namely pluripotency, axon pathfinding, Wnt, and Hippo signaling. Loss of Lhx2 caused a decrease in accessibility, specifically in hippocampal chromatin, suggesting that this factor may play a unique role in hippocampal development. We identified 14 genes that were preferentially enriched in the Hcp, for which LHX2 regulates both chromatin accessibility and mRNA expression, which have not thus far been examined in hippocampal development. Together, these results provide mechanistic insight into how LHX2 function in the Hcp may contribute to the process by which the hippocampus acquires features distinct from the neocortex.

Alternate Journal

PLoS Genet

PubMed ID

37594984

PubMed Central ID

PMC10482279

Authors

Varun Suresh
Bhavana Muralidharan
Saurabh J Pradhan
Mahima Bose
Leora D'Souza
Arpan Parichha
Puli Chandramouli Reddy
Sanjeev Galande
Shubha Tole

Keywords

LIM-Homeodomain Proteins
Neocortex
Animals
Mice
Transcription Factors
Chromatin
Transcriptome
Mammals
Hippocampus