TY - JOUR T1 - LDB1 is required for the early development of the dorsal telencephalon and the thalamus JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0356-18.2019 SP - ENEURO.0356-18.2019 AU - Veena Kinare AU - Suranjana Pal AU - Shubha Tole Y1 - 2019/02/26 UR - http://www.eneuro.org/content/early/2019/02/25/ENEURO.0356-18.2019.abstract N2 - LDB1 is a protein cofactor that participates in several multiprotein complexes with transcription factors that regulate mouse forebrain development. Since Ldb1 null mutants display early embryonic lethality, we used a conditional knockout strategy to examine the role of LDB1 in early forebrain development using multiple Cre lines. Loss of Ldb1 from E8.75 using Foxg1Cre caused a disruption of midline boundary structures in the dorsal telencephalon. While this Cre line gave the expected pattern of recombination of the floxed Ldb1 locus, unexpectedly, standard Cre lines that act from E10.5 (Emx1Cre) and E11.5 (NesCre) did not show efficient or complete recombination in the dorsal telencephalon by E12.5. Intriguingly, this effect was specific to the Ldb1 floxed allele, since three other lines including floxed Ai9 and mTmG reporters, and a floxed Lhx2 line, each displayed the expected spatial patterns of recombination. Furthermore, the incomplete recombination of the floxed Ldb1 locus using NesCre was limited to the dorsal telencephalon, while the ventral telencephalon and the diencephalon displayed the expected loss of Ldb1. This permitted us to examine the requirement for LDB1 in the development of the thalamus in a context wherein the cortex continued to express Ldb1. We report that the somatosensory VB nucleus is profoundly shrunken upon loss of LDB1. Our findings highlight the unusual nature of the Ldb1 locus in terms of recombination efficiency, and also report a novel role for LDB1 during the development of the thalamus.Significance statement The role of transcriptional co-factor LDB1 in mouse forebrain development was examined using a floxed Ldb1 line and standard Cre driver lines Foxg1Cre, Emx1Cre, and NesCre. Foxg1Cre revealed that LDB1 is a key regulator of early telencephalic midline development. Curiously, the floxed Ldb1 locus appeared to be selectively resistant to Cre-mediated recombination in the dorsal telencephalon using Emx1Cre and NesCre. Recombination improved with time in the case of Emx1Cre. NesCre recombined the floxed Ldb1 locus efficiently in the ventral telencephalon and in the diencephalon, where a critical requirement for this factor in the development of the somatosensory VB nucleus of the thalamus was revealed. Our findings highlight the importance of assessing the extent of recombination when interpreting conditional loss-of-function phenotypes. ER -