CEMO monthly seminar - Mathilde Toch

CEMO is delighted to announce the seminars of the department that will be given by PhD student and Postdoc.

The seminar is followed by a lunch (kindly provided by the department) in order to allow everybody to interact and promote collaboration between labs.

Agenda:

12:00 - "Targets and mechanisms of action of the Onecut transcription factors in the diversification of spinal motor neurons during embryonic development" - Mathilde Toch (Neural differentiation group)

Abstract

During embryonic development, spinal motor neurons (MNs) diversify into different subsets characterized by distinct molecular identity, localization and connectivity. The diversification of MN is controlled by several transcription factors, including Onecut factors. These factors are transcriptional activators that regulate the diversification of MNs by controlling directly the expression of the Isl1 gene. However, other targets of the Onecut factors in MNs are unknown and the mechanisms whereby they regulated Isl1 expression remains only partly deciphered.

To identify genes downstream of Onecut factors during MN development, we generated conditional double knock-­out (cdKO) embryos wherein Onecut factors are specifically depleted in MNs and we compared the transcriptome of control or cdKO MNs using RNA sequencing. Our results show alterations in the expression of Nkx6.2, Bhlhb4 and Ldb2 genes. These genes might be implicated at different levels in MN differentiation.

Furthermore, Onecut factors directly stimulate the expression of the MN determinant Isl1. The implication of Onecut cofactors, namely CBP and p300, in this process remains unsolved. Using chromatin immunoprecipitation, we observed that both cofactors are preferentially bound, as Onecut proteins, to the CREST2 enhancer of Isl1. Using co-­electroporation of chicken embryonic spinal cord, we demonstrated that the activation of the CREST2 enhancer depends on CBP and p300 activity and this activity is required for the stimulation of Isl1 expression by Onecut factors. Taken together, these data suggest that CBP and p300 contribute to the maintenance of Isl1 expression by the Onecut factors in MNs.

12:45 - Q&A session

13:00 - Lunch