Laboratory of Neural Differentiation (NEDI)
Last update :
June 2022
PhD students
Karolina Uwantege Kabayiza (PhD student)
In addition to motor neurons and ventral interneurons, the Onecut factors are present in subsets of interneuron populations located in the dorsal regions of the developing spinal cord. The aims of my work are 1) to describe the expression pattern of the Onecut factors in dorsal interneurons and to determine whether these markers may be instrumental in defining subclasses of these neuronal populations; 2) to assess whether Onecut factors play a role in the development of these cell populations (Kabayiza et al., 2017).
In the spinal cord, the Onecut factors are present in subpopulations of the four classes of ventral interneurons identified to date. However, the particular characteristics of these OC+ cells and the roles played by the Onecut factors in their development remain unknown. The goal of my project is to characterize the molecular and cellular mechanisms controlled by the Onecut factors that regulate the differentiation and the migration of the spinal ventral interneurons (Harris et al., 2019).
Stéphanie Debrulle (PhD student)
During locomotion, different neuronal populations located in the ventral region of the spinal cord are activated. Motor neurons directly stimulate muscle contraction whereas different interneuron populations modulate and coordinate the activity of motor neurons. The segregation between motor neuron and V2 interneuron lineages depends on the paired-like:CVC transcription factor Chx10. However, we showed that the Chx10 paralog Vsx1 is expressed in V2 precursors before the onset of V2 differentiation. The goal of my project is to characterize the roles of Vsx1 during motor neuron/V2 interneuron development (Debrulle et al., 2020).
Gauhar Masgutova (PhD student)
In addition to motor neurons and ventral interneurons, the Onecut transcriptional activators are transiently detected in subsets of dorsal interneurons and in sensory neurons during their initial phases of development. The goal of my PhD project is to further characterize the roles that Onecut play in dorsal interneuron (Masgutova et al., 2019) and sensory neuron development and to identify their mechanisms of action.
Mathilde Toch (PhD student)
Onecut transcription factors regulate the diversification of spinal motor neurons by controlling the expression of Isl1 (Roy et al., 2012). However, additional mechanisms are likely involved in this process. To identify these mechanisms, we will compare the transcriptome of wild-type spinal cords and of spinal cords carrying a conditional activation of the 3 Onecut genes in the motor neurons. This comparison should enable to identify novel targets downstream of the Onecut factors in spinal motor neurons (Toch et al., 2020) and novel mechanisms involved in the development of these cells (Toch and Clotman, 2019).
Charlotte Baudouin (PhD student)
Vincent Rucchin (lab technician)
I provide technical support to several projects dedicated to the the molecular and cellular mechanisms involved in the differentiation, in the diversification and in the migration of spinal motor neurons and interneurons. In addition, I am in charge of several logistic aspects of the laboratory including management of the stocks, of the orders, of repositories and of databases.
Principal investigator
I am interested in the molecular and cellular mechanisms that regulate neuronal differentiation and migration during embryonic development and after CNS injury or during degenerative diseases, and in identifying methods to control this differentiation process in vitro or in vivo. My ultimate goal is to develop tools that would be useful for drug or cell therapies of CNS lesions or pathologies.
Morgane Bozet (Master student)
Multiple data from the lab and from the literature suggest that the development of neuronal populations that constitute the spinal motor circuits is coordinated by non-cell autonomous mechanisms involving molecular crosstalk between these cells. Using conditional mutants for the Onecut genes, I will identify non-cell autonomous mechanisms wherein these factors are potentially involved.
Ventral interneurons of the spinal cord constitute networks that contribute to the control of locomotion, and collectively form a highly heterogeneous neuronal population in terms of molecular, electrophysiological and functional properties. During development, four cardinal ventral interneuron populations are generated and subsequently diversify in multiple subsets, the function of which remains partly elusive. My project focuses on the generation of novel genetic mouse models to characterize the genetic lineage of specific V2 interneuron subsets and to address the functional role played by these cell populations in spinal locomotor networks (Baudouin et al., 2021).
Barbara Pelosi (Postdoc fellow)
Ventral spinal interneurons play an important role in the coordination of motor neuron activity and thereby in the control of body movements. Observations made in our laboratory suggest that the development of these interneurons is regulated in a non-cell autonomous manner, and that this process could be controlled by the Onecut transcription factors. The main goal of my project is to identify non-cell autonomous mechanisms that contribute to the differentiation of spinal ventral interneurons during embryonic mouse development (Francius et al., 2016).
Maria Hidalgo Figueroa (Postdoc fellow)
The Onecut transcription factors are present in subsets of each population of ventral interneurons during spinal cord development. My Master thesis project is to characterize the distribution of these factors in these subsets of ventral interneurons, and to determine the roles exerted by the Onecut factors in their development.
Amandine Colin (Master student)
Onecut factors are present in numerous neuronal populations during embryonic development. The inactivation of Hnf6 results in locomotion defects characterized by a transient paresis of the hindlimbs. I am interested in two distinct late mechanisms whereby HNF-6 contributes to the formation of circuits that control locomotion. First, I study the role of HNF-6 in the formation of the neuromuscular junctions. Second, I investigate the expression and the function of the Onecut factors during the postnatal phase of cerebellum development.
Emilie Audouard (PhD student)
Understanding how neuronal networks that control posture and movements are generated and organized within the embryonic spinal cord is an exciting challenge for developmental neurobiology. My project focuses on the roles of Onecut transcription factors during neuronal differentiation in the embryonic ventral spinal cord, i.e. in spinal motor neurons and ventral interneurons. To address this question, I perform immunolabelings and loss- or gain-of-function experiments involving Hnf6/Oc2 knockout mouse embryos or chick embryo electroporation, respectively.
Cédric Francius (Postdoc fellow)
During my master thesis, I study the expression and the roles of Hes2, an atypical repressor among the Hes family, in the development of the ventral interneurons of the spinal cord. The expression of Hes2 will be characterized by in situ hybridization and by the detection of beta-galactosidase in Hes2-LacZ embryos. The roles of Hes2 will be studied by loss-of-function in mouse Hes2-/- embryos and by gain-of-function after chick embryonic spinal cord electroporation.
Guillaume Courtoy (Master student)
I studied the roles of the Onecut transcription factors during the differentiation of spinal motor neurons. I showed that Onecut factors are required to maintain Isl-1 expression in newly-born motor neurons. Combined loss of Onecut factors and Isl-1 results in the production of an excess of visceral motor neurons at the expenses of somatic motor neurons, and in fate conversion of LMCm into LMCl neurons. I also identified Sip1 as an additional regulator of the differentiation of visceral motor neurons. These studies elucidate a comprehensive model of the coordinate action of multiple transcriptional regulators of spinal motor neuron differentiation.
Agnès Roy (PhD student)
I investigated the roles of the Onecut transcription factors in the development of the encephalon, focusing on the development of catecholaminergic populations that are affected in the Hnf6/OC2 double knockout embryos: the dopaminergic A13 nucleus and the noradrenergic Locus Coeruleus. I was particularly interested in studying the potential molecular crosstalk between the Locus Coeruleus and an adjacent population also affected in these mutants, the Mesencephalic Trigeminal Nucleus.
Agnès Espana (PhD student)
Audrey Harris (PhD student)
NEDI lab members
Locomotor circuits in the ventral spinal cord are constituted of motor neurons and of multiple pre-motor interneurons. Several experiments in the mouse demonstrated the existence of additional pre-motor populations that remain to be characterized. The host laboratory recently uncovered that the transcriptional repressor Visual Homeobox gene 1 (Vsx1) is transiently expressed in all the spinal V2 interneuron precursors during mouse embryonic development (Francius et al., 2016). Using a transgenic Vsx1-CreERT2 mouse line (Baudouin et al., 2021), I will complete the characterization of the V2 spinal interneurons
In the spinal cord, the Onecut transcription factors are present in motor neurons and in ventral and dorsal interneurons, controling their diversification and distribution. However, observations in our laboratory demonstrate that they regulate the development of some ventral populations in a non-cell autonomous manner. The goal of my project is to identify molecules that participate in this non-cell autonomous mechanism and to determine their contribution to interneuron development and to the formation of the locomotor circuits in the spinal cord.
Locomotion is regulated by complex spinal networks composed of interacting motor neurons and interneurons. The mechanisms that control the formation of these circuits during embryonic development are tightly regulated.Lineage-tracing of spinal V2 interneurons enabled the identification of multiple genes expressed in this population, among which the Arid3 transcription factors. During my PhD thesis, I will study the expression and the roles of the Arid3 factors during differentiation of ventral neuronal populations of the spinal cord, with a focus on V2c interneurons.
Alexia Clavier (Master student)
Onecut transcription factors regulate the differentiation of spinal motor neurons. However, the genes controlled by the Onecut factors in this process remain largely unknown. Based on a RNAseq experiment that did compare the transcriptome of wildtype or Onecut-deficient motor neurons, I will investigate the expression and the possible function of genes downstream of Onecut factors during motor neuron development.
Postdoctoral researcher
Previous work in the host laboratory evidenced that signals produced in spinal motor neurons under the control of Onecut transcription factors are involved in the regulation of spinal interneurons differentiation. Moreover, spinal interneurons have been hypothesized to participate in regenerative processes after spinal cord injury (SCI), by reorganizing neuronal networks located at the lesion site as an attempt to recover the functionality of the tissue. Taking both ideas into account, I hypothesize that both cell autonomous and non-cell autonomous developmental processes could be reactivated after a SCI. Thus, the study of the specific molecules involved in these processes at early stages of development would be pivotal for their potential use after a SCI.
Master student
Luca Goffin
Numerous factors regulate the differentiation and migration of the spinal neuronal populations. Among these are the Onecut factors, present in motor neurons and in ventral or dorsal interneurons of the embryonic spinal cord. Previous observations in the lab highlighted a non-cell autonomous regulation of interneuron differentiation by the Onecut factors. Several genes potentially involved in this extrinsic regulation were identified. Their expression pattern in different neuronal populations is altered when Onecut factors are suppressed specifically from the motor neurons. During my Master thesis, I will investigate the consequences of overexpressing one of these genes in the motor neurons using chicken embryonic spinal cord electroporation.
Alumni