Onecut transcription factors act upstream of Isl1 to regulate spinal motoneuron diversification

• DOI: 10.1242/dev.078501
• Publication Date: 2012-07-26T02:52:50Z
• Authors: Agnès Roy; Cédric Francius; David L. Rousso; Eve Seuntjens; Joke Debruyn; Georg Luxenhofer; Andrea B. Huber; Danny Huylebroeck; Bennett G. Novitch; Frédéric Clotman
• Keywords: Motor Neurons; Chromatin Immunoprecipitation; 0303 health sciences; LIM-Homeodomain Proteins; Fluorescent Antibody Technique; Gene Expression Regulation, Developmental; Cell Differentiation; Chick Embryo; Mice; 03 medical and health sciences; Electroporation; Spinal Cord; Onecut Factors ; Isl1 ; Sip1 ; Neuronal Diversification ; Spinal Cord ; Cns Development; Animals; In Situ Hybridization; DNA Primers; Onecut Transcription Factors; Transcription Factors

During development, spinal motoneurons (MNs) diversify into a variety of subtypes that are specifically dedicated to the motor control particular sets skeletal muscles or visceral organs. MN diversification depends on coordinated action several transcriptional regulators including LIM-HD factor Isl1, which is crucial for survival and fate determination. However, how these cooperate establish each subtype remains poorly understood. Here, using phenotypic analyses single compound mutant mouse embryos combined with gain-of-function experiments in chick embryonic cord, we demonstrate activators Onecut family critically regulate during cord development. We provide evidence factors directly stimulate Isl1 expression specific therefore required maintain production at time diversification. In absence factors, observed major alterations decision characterized by conversion somatic MNs thoracic levels medial lateral columns innervate limbs. Furthermore, identify Sip1 (Zeb2) as novel developmental regulator differentiation. Taken together, data elucidate comprehensive model wherein multiple aspects They also shed light late roles decision.