Slit and semaphorin signaling governed by Islet transcription factors positions motor neuron somata within the neural tube (original) (raw)
Related papers
Isl1 Is required for multiple aspects of motor neuron development
The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in multiple organs and plays essential roles during embryogenesis. Isl1 is required for the survival and specification of spinal cord motor neurons. Due to early embryonic lethality and loss of motor neurons, the role of Isl1 in other aspects of motor neuron development remains unclear. In this study, we generated Isl1 mutant mouse lines expressing graded doses of Isl1. Our study has revealed essential roles of Isl1 in multiple aspects of motor neuron development, including motor neuron cell body localization, motor column formation and axon growth. In addition, Isl1 is required for survival of cranial ganglia neurons.
Spinal neurons require Islet1 for subtype-specific differentiation of electrical excitability
Neural development, 2014
In the spinal cord, stereotypic patterns of transcription factor expression uniquely identify neuronal subtypes. These transcription factors function combinatorially to regulate gene expression. Consequently, a single transcription factor may regulate divergent development programs by participation in different combinatorial codes. One such factor, the LIM-homeodomain transcription factor Islet1, is expressed in the vertebrate spinal cord. In mouse, chick and zebrafish, motor and sensory neurons require Islet1 for specification of biochemical and morphological signatures. Little is known, however, about the role that Islet1 might play for development of electrical membrane properties in vertebrates. Here we test for a role of Islet1 in differentiation of excitable membrane properties of zebrafish spinal neurons. We focus our studies on the role of Islet1 in two populations of early born zebrafish spinal neurons: ventral caudal primary motor neurons (CaPs) and dorsal sensory Rohon-Be...
Neuropilin receptors guide distinct phases of sensory and motor neuronal segmentation
Development, 2009
The segmented trunk peripheral nervous system is generated by ventrally migrating neural crest cells that exclusively invade the anterior sclerotome and differentiate into metameric dorsal root and sympathetic ganglia. Meanwhile, ventral spinal motor axons also project through the somites in a segmental fashion. How peripheral nervous system segmentation is generated is unknown. We previously showed that neuropilin 2 (Nrp2)/semaphorin 3F (Sema3F)signaling is required for segmental neural crest migration, but not for metameric dorsal root gangliogenesis. We now expand these results to show that Nrp2 patterns initial motor axon outgrowth as well. Later, Nrp1/Sema3A signaling is essential for segmental dorsal root gangliogenesis and motor axonal fasciculation into ventral roots. Strikingly, Nrp/Sema signaling is not required for sympathetic ganglia segmentation. These data show that Nrp2 and Nrp1 work together to produce segmentation of sensory and motor nerves, and that dorsal periphe...
Development (Cambridge, England), 2014
The proper balance of excitatory and inhibitory neurons is crucial for normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors (TFs), Ascl1 and Ptf1a, have contrasting functions in specifying these neurons. To understand how Ascl1 and Ptf1a function in this process, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a directly regulate distinct homeodomain TFs that specify excitatory or inhibitory neuronal fates. In addition, Ascl1 directly regulates genes with roles in several steps of the neurogenic program, including Notch signaling, neuronal differentiation, axon guidance and synapse formation. By contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover...
Development, 2007
Class III semaphorins (SemaIIIs) are intercellular cues secreted by surrounding tissues to guide migrating cells and axons in the developing organism. This chemotropic activity is crucial for the formation of nerves and vasculature. Intriguingly, SemaIIIs are also synthesized by neurons during axon pathfinding, but their function as intrinsic cues remains unknown. We have explored the role of Sema3A expression in motoneurons during spinal nerve development. Loss- and gain-of-function in the neural tube of the chick embryo were undertaken to target Sema3A expression in motoneurons while preserving Sema3A sources localized in peripheral tissues, known to provide important repulsive information for delineating the routes of motor axons towards their ventral or dorsal targets. Strikingly, Sema3A overexpression induced defasciculation and exuberant growth of motor axon projections into these normally non-permissive territories. Moreover, knockdown studies showed that motoneuronal Sema3A ...