Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries Journal Article


Author(s): Mayer, Christian; Jaglin, Xavier H; Cobbs, Lucy V; Bandler, Rachel C; Streicher, Carmen; Cepko, Constance L; Hippenmeyer, Simon; Fishell, Gord J
Article Title: Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries
Affiliation IST Austria
Abstract: The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute.
Keywords: DNA barcoding; cell migration; cellular distribution; protein expression; Mitosis; Forebrain; Hippocampus; Neocortex; Corpus Striatum; Globus Pallidus; interneuron; Olfactory Bulb; stem cell; cell fate; GABAergic system; hypothalamus; virus envelope protein; transcription factor Nkx2.2; virus vector; asymmetric cell division; brain cortex; brain function; clonal variation; DNA library; gene silencing; medial ganglionic eminence; median eminence; oligodendrocyte culture; Retroviridae; septum pellucidum; subventricular zone; telencephalon
Journal Title: Neuron
Volume: 87
Issue 5
ISSN: 0896-6273
Publisher: Elsevier  
Date Published: 2015-09-02
Start Page: 989
End Page: 998
URL:
DOI: 10.1016/j.neuron.2015.07.011
Notes: Research in the G.F. laboratory is supported by NIH (NS 081297, MH095147, and P01NS074972) and the Simons Foundation. Research in the S.H. laboratory is supported by the European Union (FP7-CIG618444). C.M. is supported by EMBO ALTF (1295-2012). X.H.J. is supported by EMBO (ALTF 303-2010) and HFSP (LT000078/2011-L).
Open access: yes (repository)